{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:38:39Z","timestamp":1792096719216,"version":"4.4.0"},"reference-count":320,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["CX002436"],"award-info":[{"award-number":["CX002436"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Missouri","award":["CX002436"],"award-info":[{"award-number":["CX002436"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Metabolic dysfunction-associated steatotic liver disease (MASLD) impacts nearly a quarter of the world\u2019s population and encompasses a range of disease states, from simple steatosis to more advanced stages like metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, and cirrhosis. A key driver of disease progression is mitochondrial dysfunction, characterized by impaired fatty acid oxidation and an overall decline in mitochondrial health. Emerging evidence has implicated ceramides\u2014bioactive sphingolipids that serve roles in apoptotic pathways and as signals of nutrient excess\u2014as important contributors to this dysfunction. Ceramide accumulation within mitochondria mirrors impairments seen in MASLD, specifically elevations in oxidative stress, disrupted fatty acid oxidation, and impaired mitochondrial dynamics. Ceramides may serve as an important molecular link between nutrient overload and mitochondrial dysfunction in the pathogenesis of MASLD. Given the limited availability of effective pharmacologic therapies for MASLD, lifestyle interventions like dietary modification and physical activity remain the cornerstone of disease management worldwide. In this review, we provide an overview of the current understanding of the role of ceramides in mediating the effects of diet and exercise on MASLD through their influence on mitochondrial health.<\/jats:p>","DOI":"10.3390\/nu17182972","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T05:59:51Z","timestamp":1758088791000},"page":"2972","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Effects of Diet and Exercise on Mitochondrial Health in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Role of Ceramides"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1029-0913","authenticated-orcid":false,"given":"Jonas M.","family":"McCaffrey","sequence":"first","affiliation":[{"name":"School of Medicine, University of Missouri, Columbia, MO 65212, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5646-9014","authenticated-orcid":false,"given":"Jamal A.","family":"Ibdah","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65212, USA"},{"name":"Harry S. Truman Memorial Veterans Medical Center, Columbia, MO 65201, USA"},{"name":"Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65212, USA"},{"name":"Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65212, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1002\/hep.23280","article-title":"Obesity and Nonalcoholic Fatty Liver Disease: Biochemical, Metabolic, and Clinical Implications","volume":"51","author":"Fabbrini","year":"2010","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.jhep.2025.02.033","article-title":"Integrative Metabolism in MASLD and MASH: Pathophysiology and Emerging Mechanisms","volume":"83","author":"Steinberg","year":"2025","journal-title":"J. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/j.metabol.2016.01.012","article-title":"Epidemiology and Natural History of Non-Alcoholic Fatty Liver Disease","volume":"65","author":"Fazel","year":"2016","journal-title":"Metabolism"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrgastro.2017.109","article-title":"Global Burden of NAFLD and NASH: Trends, Predictions, Risk Factors and Prevention","volume":"15","author":"Younossi","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ramanathan, R., Ali, A.H., and Ibdah, J.A. (2022). Mitochondrial Dysfunction Plays Central Role in Nonalcoholic Fatty Liver Disease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23137280"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"289","DOI":"10.7570\/jomes23054","article-title":"Mitochondrial Quality Control: Its Role in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)","volume":"32","author":"Shin","year":"2023","journal-title":"J. Obes. Metab. Syndr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1042\/BJ20031819","article-title":"Subcellular Compartmentalization of Ceramide Metabolism: MAM (Mitochondria-Associated Membrane) and\/or Mitochondria?","volume":"382","author":"Bionda","year":"2004","journal-title":"Biochem. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1007\/s11745-998-0246-2","article-title":"Partial Purification and Characterization of Sphingosine N-Acyltransferase (Ceramide Synthase) from Bovine Liver Mitochondrion-Rich Fraction","volume":"33","author":"Shimeno","year":"1998","journal-title":"Lipids"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/s41569-021-00536-1","article-title":"Ceramides and Other Sphingolipids as Drivers of Cardiovascular Disease","volume":"18","author":"Choi","year":"2021","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1111\/j.1399-543X.2004.00071.x","article-title":"Skeletal Muscle Lipid Accumulation in Obesity, Insulin Resistance, and Type 2 Diabetes","volume":"5","author":"Goodpaster","year":"2004","journal-title":"Pediatr. Diabetes"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Jiang, M., Li, C., Liu, Q., Wang, A., and Lei, M. (2019). Inhibiting Ceramide Synthesis Attenuates Hepatic Steatosis and Fibrosis in Rats With Non-Alcoholic Fatty Liver Disease. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00665"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8359","DOI":"10.1074\/jbc.M807800200","article-title":"Acid Sphingomyelinase Deficiency Prevents Diet-Induced Hepatic Triacylglycerol Accumulation and Hyperglycemia in Mice","volume":"284","author":"Deevska","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kasumov, T., Li, L., Li, M., Gulshan, K., Kirwan, J.P., Liu, X., Previs, S., Willard, B., Smith, J.D., and McCullough, A. (2015). Ceramide as a Mediator of Non-Alcoholic Fatty Liver Disease and Associated Atherosclerosis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0126910"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1111\/j.1872-034X.2011.00934.x","article-title":"High Fat Diet Induced Hepatic Steatosis and Insulin Resistance: Role of Dysregulated Ceramide Metabolism","volume":"42","author":"Longato","year":"2012","journal-title":"Hepatol. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.molmet.2018.12.008","article-title":"The Role of C16:0 Ceramide in the Development of Obesity and Type 2 Diabetes: CerS6 Inhibition as a Novel Therapeutic Approach","volume":"21","author":"Raichur","year":"2019","journal-title":"Mol. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Yetukuri, L., Katajamaa, M., Medina-Gomez, G., Sepp\u00e4nen-Laakso, T., Vidal-Puig, A., and Ore\u0161i\u010d, M. (2007). Bioinformatics Strategies for Lipidomics Analysis: Characterization of Obesity Related Hepatic Steatosis. BMC Syst. Biol., 1.","DOI":"10.1186\/1752-0509-1-12"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1002\/ejlt.200405001","article-title":"A Comprehensive Classification System for Lipids","volume":"107","author":"Fahy","year":"2005","journal-title":"Eur. J. Lipid Sci. Technol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1146\/annurev-physiol-031620-093815","article-title":"Ceramides in Metabolism: Key Lipotoxic Players","volume":"83","author":"Chaurasia","year":"2021","journal-title":"Annu. Rev. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11144","DOI":"10.1016\/S0021-9258(19)49887-6","article-title":"Subcellular Localization and Membrane Topology of Serine Palmitoyltransferase, 3-Dehydrosphinganine Reductase, and Sphinganine N-Acyltransferase in Mouse Liver","volume":"267","author":"Mandon","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S91","DOI":"10.1194\/jlr.R800080-JLR200","article-title":"Bioactive Sphingolipids: Metabolism and Function","volume":"50","author":"Bartke","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/978-3-030-21162-2_4","article-title":"A Stroll Down the CerS Lane","volume":"1159","author":"Zelnik","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"15371","DOI":"10.1074\/jbc.R115.653204","article-title":"Dihydroceramides: From Bit Players to Lead Actors","volume":"290","author":"Siddique","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_23","first-page":"644","article-title":"CERT and Intracellular Trafficking of Ceramide","volume":"1771","author":"Hanada","year":"2007","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Cell Biol. Lipids"},{"key":"ref_24","first-page":"419","article-title":"Ceramide and Sphingosine 1-Phosphate in Liver Diseases","volume":"43","author":"Park","year":"2020","journal-title":"Mol. Cells"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s00018-022-04401-3","article-title":"Contribution of Specific Ceramides to Obesity-Associated Metabolic Diseases","volume":"79","author":"Hammerschmidt","year":"2022","journal-title":"Cell Mol. Life Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.cmet.2014.08.002","article-title":"Obesity-Induced CerS6-Dependent C16:0 Ceramide Production Promotes Weight Gain and Glucose Intolerance","volume":"20","author":"Turpin","year":"2014","journal-title":"Cell Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1126\/science.aav3722","article-title":"Targeting a Ceramide Double Bond Improves Insulin Resistance and Hepatic Steatosis","volume":"365","author":"Chaurasia","year":"2019","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4947","DOI":"10.1074\/jbc.M112.402719","article-title":"Ablation of Ceramide Synthase 2 Causes Chronic Oxidative Stress Due to Disruption of the Mitochondrial Respiratory Chain","volume":"288","author":"Zigdon","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1186\/s12933-022-01596-4","article-title":"Circulating Ceramides and Sphingomyelins and the Risk of Incident Cardiovascular Disease among People with Diabetes: The Strong Heart Study","volume":"21","author":"Jensen","year":"2022","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.2337\/db17-1449","article-title":"Circulating Sphingolipids, Insulin, HOMA-IR, and HOMA-B: The Strong Heart Family Study","volume":"67","author":"Lemaitre","year":"2018","journal-title":"Diabetes"},{"key":"ref_31","first-page":"671","article-title":"Ceramide Synthases as Potential Targets for Therapeutic Intervention in Human Diseases","volume":"1841","author":"Park","year":"2014","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Cell Biol. Lipids"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1016\/j.bbalip.2016.08.016","article-title":"Regulation of Glucose Homeostasis and Insulin Action by Ceramide Acyl-Chain Length: A Beneficial Role for Very Long-Chain Sphingolipid Species","volume":"1861","author":"Montgomery","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Buechler, C., and Aslanidis, C. (2020). Role of Lipids in Pathophysiology, Diagnosis and Therapy of Hepatocellular Carcinoma. Biochim. Biophys. Acta (BBA)-Mol. Cell Biol. Lipids, 1865.","DOI":"10.1016\/j.bbalip.2020.158658"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.molmed.2018.10.009","article-title":"Ceramides as Novel Disease Biomarkers","volume":"25","author":"Kurz","year":"2019","journal-title":"Trends Mol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Hilvo, M., Vasile, V.C., Donato, L.J., Hurme, R., and Laaksonen, R. (2020). Ceramides and Ceramide Scores: Clinical Applications for Cardiometabolic Risk Stratification. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.570628"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Gaggini, M., Pingitore, A., and Vassalle, C. (2021). Plasma Ceramides Pathophysiology, Measurements, Challenges, and Opportunities. Metabolites, 11.","DOI":"10.3390\/metabo11110719"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1002\/oby.21117","article-title":"Improved Insulin Sensitivity after Exercise Training Is Linked to Reduced Plasma C14:0 Ceramide in Obesity and Type 2 Diabetes","volume":"23","author":"Kasumov","year":"2015","journal-title":"Obesity"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1042\/bse0470085","article-title":"Mitochondrial Fission and Fusion","volume":"47","author":"Scott","year":"2010","journal-title":"Essays Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e13428","DOI":"10.1111\/apha.13428","article-title":"Mitochondrial Fusion Promoter Restores Mitochondrial Dynamics Balance and Ameliorates Diabetic Cardiomyopathy in an Optic Atrophy 1-Dependent Way","volume":"229","author":"Ding","year":"2020","journal-title":"Acta Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.mito.2019.11.006","article-title":"OPA1 Regulates Respiratory Supercomplexes Assembly: The Role of Mitochondrial Swelling","volume":"51","author":"Jang","year":"2020","journal-title":"Mitochondrion"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.tcb.2007.08.006","article-title":"Regulation of Mitochondrial Fusion and Division","volume":"17","author":"Cerveny","year":"2007","journal-title":"Trends Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Sumneang, N., Siri-Angkul, N., Kumfu, S., Chattipakorn, S.C., and Chattipakorn, N. (2020). The Effects of Iron Overload on Mitochondrial Function, Mitochondrial Dynamics, and Ferroptosis in Cardiomyocytes. Arch. Biochem. Biophys., 680.","DOI":"10.1016\/j.abb.2019.108241"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e12447","DOI":"10.1111\/jpi.12447","article-title":"Dynamin-Related Protein 1-Mediated Mitochondrial Fission Contributes to Post-Traumatic Cardiac Dysfunction in Rats and the Protective Effect of Melatonin","volume":"64","author":"Ding","year":"2018","journal-title":"J. Pineal Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1091\/mbc.12.8.2245","article-title":"Dynamin-Related Protein Drp1 Is Required for Mitochondrial Division in Mammalian Cells","volume":"12","author":"Smirnova","year":"2001","journal-title":"Mol. Biol. Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.bbamcr.2012.05.002","article-title":"Recent Advances into the Understanding of Mitochondrial Fission","volume":"1833","author":"Elgass","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1007\/s10495-016-1295-5","article-title":"Mitochondrial Dynamics during Cell Cycling","volume":"21","author":"Horbay","year":"2016","journal-title":"Apoptosis"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"104553","DOI":"10.1016\/j.phrs.2019.104553","article-title":"Dynamin-Related Protein 1: A Protein Critical for Mitochondrial Fission, Mitophagy, and Neuronal Death in Parkinson\u2019s Disease","volume":"151","author":"Feng","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1515\/hsz-2012-0119","article-title":"Mitophagy: Mechanisms, Pathophysiological Roles, and Analysis","volume":"393","author":"Ding","year":"2012","journal-title":"Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.cmet.2015.06.006","article-title":"Redox Homeostasis and Mitochondrial Dynamics","volume":"22","author":"Willems","year":"2015","journal-title":"Cell Metab."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1083\/jcb.200809125","article-title":"Parkin Is Recruited Selectively to Impaired Mitochondria and Promotes Their Autophagy","volume":"183","author":"Narendra","year":"2008","journal-title":"J. Cell Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.4161\/auto.24135","article-title":"After the Banquet: Mitochondrial Biogenesis, Mitophagy, and Cell Survival","volume":"9","author":"Zhu","year":"2013","journal-title":"Autophagy"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"29","DOI":"10.21775\/cimb.028.029","article-title":"PGC-1: The Energetic Regulator in Cardiac Metabolism","volume":"28","author":"Di","year":"2018","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.metabol.2017.11.001","article-title":"Coordination of Mitochondrial Biogenesis by PGC-1\u03b1 in Human Skeletal Muscle: A Re-Evaluation","volume":"79","author":"Islam","year":"2018","journal-title":"Metabolism"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1042\/bse0470069","article-title":"Regulation of Mitochondrial Biogenesis","volume":"47","author":"Jornayvaz","year":"2010","journal-title":"Essays Biochem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.tig.2018.05.009","article-title":"Mitochondrial DNA Transcription and Its Regulation: An Evolutionary Perspective","volume":"34","author":"Barshad","year":"2018","journal-title":"Trends Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/S0092-8674(00)81410-5","article-title":"A Cold-Inducible Coactivator of Nuclear Receptors Linked to Adaptive Thermogenesis","volume":"92","author":"Puigserver","year":"1998","journal-title":"Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"9079","DOI":"10.1128\/MCB.24.20.9079-9091.2004","article-title":"Estrogen-Related Receptor Alpha Directs Peroxisome Proliferator-Activated Receptor Alpha Signaling in the Transcriptional Control of Energy Metabolism in Cardiac and Skeletal Muscle","volume":"24","author":"Huss","year":"2004","journal-title":"Mol. Cell Biol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Kong, X., Wang, R., Xue, Y., Liu, X., Zhang, H., Chen, Y., Fang, F., and Chang, Y. (2010). Sirtuin 3, a New Target of PGC-1alpha, Plays an Important Role in the Suppression of ROS and Mitochondrial Biogenesis. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011707"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/nature08778","article-title":"SIRT3 Regulates Mitochondrial Fatty-Acid Oxidation by Reversible Enzyme Deacetylation","volume":"464","author":"Hirschey","year":"2010","journal-title":"Nature"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"14447","DOI":"10.1073\/pnas.0803790105","article-title":"A Role for the Mitochondrial Deacetylase Sirt3 in Regulating Energy Homeostasis","volume":"105","author":"Ahn","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.cell.2010.10.002","article-title":"Sirt3 Mediates Reduction of Oxidative Damage and Prevention of Age-Related Hearing Loss under Caloric Restriction","volume":"143","author":"Someya","year":"2010","journal-title":"Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.cmet.2011.06.009","article-title":"Deletion of the Mammalian INDY Homolog Mimics Aspects of Dietary Restriction and Protects against Adiposity and Insulin Resistance in Mice","volume":"14","author":"Birkenfeld","year":"2011","journal-title":"Cell Metab."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"21508","DOI":"10.1074\/jbc.M002522200","article-title":"Molecular Cloning and Characterization of a Human Mitochondrial Ceramidase *","volume":"275","author":"Roddy","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/S0014-5793(00)02332-2","article-title":"Occurrence of Ceramides and Neutral Glycolipids with Unusual Long-Chain Base Composition in Purified Rat Liver Mitochondria","volume":"488","author":"Ardail","year":"2001","journal-title":"FEBS Lett."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Babiychuk, E.B., Atanassoff, A.P., Monastyrskaya, K., Brandenberger, C., Studer, D., Allemann, C., and Draeger, A. (2011). The Targeting of Plasmalemmal Ceramide to Mitochondria during Apoptosis. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023706"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1042\/bj3410233","article-title":"The Mitochondrial Permeability Transition Pore and Its Role in Cell Death","volume":"341","author":"Crompton","year":"1999","journal-title":"Biochem. J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0005-2728(98)00110-8","article-title":"Mitochondria as Regulators of Apoptosis: Doubt No More","volume":"1366","author":"Susin","year":"1998","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"7248","DOI":"10.1016\/S0021-9258(19)39106-9","article-title":"Phospholipid Synthesis in a Membrane Fraction Associated with Mitochondria","volume":"265","author":"Vance","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"25843","DOI":"10.1074\/jbc.R200009200","article-title":"De Novo Sphingolipid Biosynthesis: A Necessary, but Dangerous, Pathway","volume":"277","author":"Merrill","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.1073\/pnas.051631998","article-title":"Organellar Relationships in the Golgi Region of the Pancreatic Beta Cell Line, HIT-T15, Visualized by High Resolution Electron Tomography","volume":"98","author":"Marsh","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"25985","DOI":"10.1016\/S0021-9258(19)74483-4","article-title":"Involvement of Mitochondrial Contact Sites in the Subcellular Compartmentalization of Phospholipid Biosynthetic Enzymes","volume":"268","author":"Ardail","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"16758","DOI":"10.1074\/jbc.M009331200","article-title":"Biochemical Characterization of the Reverse Activity of Rat Brain Ceramidase. A CoA-Independent and Fumonisin B1-Insensitive Ceramide Synthase","volume":"276","author":"Birbes","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"25352","DOI":"10.1074\/jbc.M110.214866","article-title":"Novel Pathway of Ceramide Production in Mitochondria: Thioesterase and Neutral Ceramidase Produce Ceramide from Sphingosine and Acyl-CoA","volume":"286","author":"Novgorodov","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1042\/BJ20041627","article-title":"A Mitochondrial Pool of Sphingomyelin Is Involved in TNF\u03b1-Induced Bax Translocation to Mitochondria","volume":"386","author":"Birbes","year":"2005","journal-title":"Biochem. J."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"24154","DOI":"10.1074\/jbc.272.39.24154","article-title":"Direct Inhibition of Mitochondrial Respiratory Chain Complex III by Cell-Permeable Ceramide","volume":"272","author":"Gudz","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"6660","DOI":"10.1021\/bi9924415","article-title":"Ceramide Interaction with the Respiratory Chain of Heart Mitochondria","volume":"39","author":"Cocco","year":"2000","journal-title":"Biochemistry"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"11369","DOI":"10.1074\/jbc.272.17.11369","article-title":"Direct Effect of Ceramide on the Mitochondrial Electron Transport Chain Leads to Generation of Reactive Oxygen Species. Role of Mitochondrial Glutathione","volume":"272","author":"Colell","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"340","DOI":"10.2174\/187152012800228661","article-title":"Ceramide and Apoptosis: Exploring the Enigmatic Connections between Sphingolipid Metabolism and Programmed Cell Death","volume":"12","author":"Mullen","year":"2012","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.1096\/fj.07-092981","article-title":"A Role for Ceramide in Driving Cancer Cell Resistance to Doxorubicin","volume":"22","author":"Liu","year":"2008","journal-title":"FASEB J."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: A Review of Programmed Cell Death","volume":"35","author":"Elmore","year":"2007","journal-title":"Toxicol. Pathol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.advms.2023.10.004","article-title":"Ceramides and Their Roles in Programmed Cell Death","volume":"68","author":"Mezencev","year":"2023","journal-title":"Adv. Med. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1111\/j.1600-0854.2008.00800.x","article-title":"Fluorescent Annexin A1 Reveals Dynamics of Ceramide Platforms in Living Cells","volume":"9","author":"Babiychuk","year":"2008","journal-title":"Traffic"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1126\/science.8456305","article-title":"Programmed Cell Death Induced by Ceramide","volume":"259","author":"Obeid","year":"1993","journal-title":"Science"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/s41580-019-0173-8","article-title":"Mitochondria as Multifaceted Regulators of Cell Death","volume":"21","author":"Bock","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s10495-009-0449-0","article-title":"Ceramide and Activated Bax Act Synergistically to Permeabilize the Mitochondrial Outer Membrane","volume":"15","author":"Ganesan","year":"2010","journal-title":"Apoptosis"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"4009","DOI":"10.1038\/sj.onc.1205497","article-title":"Ceramide Induces Mitochondrial Activation and Apoptosis via a Bax-Dependent Pathway in Human Carcinoma Cells","volume":"21","author":"Wieder","year":"2002","journal-title":"Oncogene"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Lee, H., Rotolo, J.A., Mesicek, J., Penate-Medina, T., Rimner, A., Liao, W.-C., Yin, X., Ragupathi, G., Ehleiter, D., and Gulbins, E. (2011). Mitochondrial Ceramide-Rich Macrodomains Functionalize Bax upon Irradiation. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019783"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1194\/jlr.M012161","article-title":"Mitochondrially Targeted Ceramides Preferentially Promote Autophagy, Retard Cell Growth, and Induce Apoptosis","volume":"52","author":"Hou","year":"2011","journal-title":"J. Lipid Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1038\/s41467-019-09654-4","article-title":"Ceramides Bind VDAC2 to Trigger Mitochondrial Apoptosis","volume":"10","author":"Dadsena","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.cmet.2016.11.004","article-title":"Enhanced Respiratory Chain Supercomplex Formation in Response to Exercise in Human Skeletal Muscle","volume":"25","author":"Greggio","year":"2017","journal-title":"Cell Metab."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1096\/fj.02-0951com","article-title":"Raising Ca2+ in L6 Myotubes Mimics Effects of Exercise on Mitochondrial Biogenesis in Muscle","volume":"17","author":"Ojuka","year":"2003","journal-title":"FASEB J."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Roberts, F.L., and Markby, G.R. (2021). New Insights into Molecular Mechanisms Mediating Adaptation to Exercise; A Review Focusing on Mitochondrial Biogenesis, Mitochondrial Function, Mitophagy and Autophagy. Cells, 10.","DOI":"10.3390\/cells10102639"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"111099","DOI":"10.1016\/j.cellsig.2024.111099","article-title":"Ceramides and Mitochondrial Homeostasis","volume":"117","author":"Ding","year":"2024","journal-title":"Cell. Signal."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e2025347118","DOI":"10.1073\/pnas.2025347118","article-title":"Ceramide Accumulation Induces Mitophagy and Impairs \u03b2-Oxidation in PINK1 Deficiency","volume":"118","author":"Vos","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Gaudioso, A., Garcia-Rozas, P., Casarejos, M.J., Pastor, O., and Rodriguez-Navarro, J.A. (2019). Lipidomic Alterations in the Mitochondria of Aged Parkin Null Mice Relevant to Autophagy. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.00329"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1038\/nchembio.1059","article-title":"Ceramide Targets Autophagosomes to Mitochondria and Induces Lethal Mitophagy","volume":"8","author":"Sentelle","year":"2012","journal-title":"Nat. Chem. Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/sj.emboj.7601963","article-title":"Fission and Selective Fusion Govern Mitochondrial Segregation and Elimination by Autophagy","volume":"27","author":"Twig","year":"2008","journal-title":"EMBO J."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0014-5793(03)00124-8","article-title":"Fusion of Mitochondria in Mammalian Cells Is Dependent on the Mitochondrial Inner Membrane Potential and Independent of Microtubules or Actin","volume":"538","author":"Mattenberger","year":"2003","journal-title":"FEBS Lett."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.freeradbiomed.2022.07.001","article-title":"miR-495\u20133p Regulates Sphingolipid Metabolic Reprogramming to Induce Sphk1\/Ceramide Mediated Mitophagy and Apoptosis in NSCLC","volume":"189","author":"Arora","year":"2022","journal-title":"Free Radic. Biol. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1007\/s00125-021-05430-6","article-title":"Exercise Training Improves Mitochondrial Respiration and Is Associated with an Altered Intramuscular Phospholipid Signature in Women with Obesity","volume":"64","author":"Mendham","year":"2021","journal-title":"Diabetologia"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Jamil, M., and Cowart, L.A. (2023). Sphingolipids in Mitochondria\u2014From Function to Disease. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1302472"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Cogolludo, A., Villamor, E., Perez-Vizcaino, F., and Moreno, L. (2019). Ceramide and Regulation of Vascular Tone. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20020411"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1038\/s41401-019-0328-3","article-title":"Acid Sphingomyelinase Downregulation Alleviates Vascular Endothelial Leptin Resistance in Rats","volume":"41","author":"Cai","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.jcmgh.2018.09.011","article-title":"Macrophage Raptor Deficiency-Induced Lysosome Dysfunction Exacerbates Nonalcoholic Steatohepatitis","volume":"7","author":"Liu","year":"2019","journal-title":"Cell Mol. Gastroenterol. Hepatol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/j.metabol.2015.12.012","article-title":"The Multiple-Hit Pathogenesis of Non-Alcoholic Fatty Liver Disease (NAFLD)","volume":"65","author":"Buzzetti","year":"2016","journal-title":"Metabolism"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1002\/hep.31518","article-title":"Multiple Parallel Hits Hypothesis in Nonalcoholic Fatty Liver Disease: Revisited After a Decade","volume":"73","author":"Tilg","year":"2021","journal-title":"Hepatology"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1089\/ars.2010.3395","article-title":"Chronic Exposure to a High-Fat Diet Induces Hepatic Steatosis, Impairs Nitric Oxide Bioavailability, and Modifies the Mitochondrial Proteome in Mice","volume":"15","author":"Eccleston","year":"2011","journal-title":"Antioxid. Redox Signal"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.jhep.2021.04.013","article-title":"Hepatic Lipidomic Remodeling in Severe Obesity Manifests with Steatosis and Does Not Evolve with Non-Alcoholic Steatohepatitis","volume":"75","author":"Ooi","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1002\/hep4.1188","article-title":"Metabolomic-Based Noninvasive Serum Test to Diagnose Nonalcoholic Steatohepatitis: Results from Discovery and Validation Cohorts","volume":"2","author":"Mayo","year":"2018","journal-title":"Hepatol. Commun."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1002\/hep.21763","article-title":"A Lipidomic Analysis of Nonalcoholic Fatty Liver Disease","volume":"46","author":"Puri","year":"2007","journal-title":"Hepatology"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1002\/hep.29359","article-title":"The Presence and Severity of Nonalcoholic Steatohepatitis Is Associated with Specific Changes in Circulating Bile Acids","volume":"67","author":"Puri","year":"2018","journal-title":"Hepatology"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1172\/JCI23621","article-title":"Sources of Fatty Acids Stored in Liver and Secreted via Lipoproteins in Patients with Nonalcoholic Fatty Liver Disease","volume":"115","author":"Donnelly","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"G194","DOI":"10.1152\/ajpgi.00413.2005","article-title":"Lipid Metabolism and Liver Inflammation. I. Hepatic Fatty Acid Uptake: Possible Role in Steatosis","volume":"290","author":"Bradbury","year":"2006","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"4753","DOI":"10.1210\/jc.2006-0587","article-title":"Review: The Role of Insulin Resistance in Nonalcoholic Fatty Liver Disease","volume":"91","author":"Utzschneider","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/nrgastro.2010.191","article-title":"Animal Models of Nonalcoholic Fatty Liver Disease","volume":"8","author":"Hebbard","year":"2011","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/nrm2391","article-title":"Adipocyte Dysfunctions Linking Obesity to Insulin Resistance and Type 2 Diabetes","volume":"9","author":"Guilherme","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.cld.2009.07.009","article-title":"Role of Insulin Resistance and Lipotoxicity in Non-Alcoholic Steatohepatitis","volume":"13","author":"Cusi","year":"2009","journal-title":"Clin. Liver Dis."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"14205","DOI":"10.3748\/wjg.v20.i39.14205","article-title":"Oxidative Stress, Cardiolipin and Mitochondrial Dysfunction in Nonalcoholic Fatty Liver Disease","volume":"20","author":"Paradies","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0378-1119(01)00814-9","article-title":"Reactive Oxygen Species Affect Mitochondrial Electron Transport Complex I Activity through Oxidative Cardiolipin Damage","volume":"286","author":"Paradies","year":"2002","journal-title":"Gene"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"119328","DOI":"10.1016\/j.lfs.2021.119328","article-title":"A Review on Molecular Mechanism of Alcoholic Liver Disease","volume":"274","author":"Namachivayam","year":"2021","journal-title":"Life Sci."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1194\/jlr.R700007-JLR200","article-title":"Thematic Review Series: Adipocyte Biology. Adipocyte Stress: The Endoplasmic Reticulum and Metabolic Disease","volume":"48","author":"Gregor","year":"2007","journal-title":"J. Lipid Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.clinbiochem.2015.06.023","article-title":"Gut-Liver Axis, Nutrition, and Non-Alcoholic Fatty Liver Disease","volume":"48","author":"Kirpich","year":"2015","journal-title":"Clin. Biochem."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Namjou, B., Lingren, T., Huang, Y., Parameswaran, S., Cobb, B.L., Stanaway, I.B., Connolly, J.J., Mentch, F.D., Benoit, B., and Niu, X. (2019). GWAS and Enrichment Analyses of Non-Alcoholic Fatty Liver Disease Identify New Trait-Associated Genes and Pathways across eMERGE Network. BMC Med., 17.","DOI":"10.1186\/s12916-019-1364-z"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1053\/j.gastro.2009.01.050","article-title":"Heritability of Nonalcoholic Fatty Liver Disease","volume":"136","author":"Schwimmer","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1080\/14728222.2021.2018418","article-title":"PNPLA3 as a Therapeutic Target for Fatty Liver Disease: The Evidence to Date","volume":"25","author":"Cherubini","year":"2021","journal-title":"Expert. Opin. Ther. Targets"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"102336","DOI":"10.1016\/j.ceca.2020.102336","article-title":"Role of Mitochondria in Liver Metabolic Health and Diseases","volume":"94","author":"Morio","year":"2021","journal-title":"Cell Calcium"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1053\/j.gastro.2013.11.049","article-title":"Increased De Novo Lipogenesis Is a Distinct Characteristic of Individuals With Nonalcoholic Fatty Liver Disease","volume":"146","author":"Lambert","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"3723","DOI":"10.1042\/BCJ20210071","article-title":"SREBP-1c and Lipogenesis in the Liver: An Update1","volume":"478","author":"Phan","year":"2021","journal-title":"Biochem. J."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Sanders, F.W.B., Acharjee, A., Walker, C., Marney, L., Roberts, L.D., Imamura, F., Jenkins, B., Case, J., Ray, S., and Virtue, S. (2018). Hepatic Steatosis Risk Is Partly Driven by Increased de Novo Lipogenesis Following Carbohydrate Consumption. Genome Biol., 19.","DOI":"10.1186\/s13059-018-1439-8"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1080\/10409238.2017.1337706","article-title":"Sphingosine Kinase and Sphingosine-1-Phosphate in Liver Pathobiology","volume":"52","author":"Rohrbach","year":"2017","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.jhep.2009.11.030","article-title":"Mitochondrial Dysfunction Precedes Insulin Resistance and Hepatic Steatosis and Contributes to the Natural History of Non-Alcoholic Fatty Liver Disease in an Obese Rodent Model","volume":"52","author":"Rector","year":"2010","journal-title":"J. Hepatol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1113\/jphysiol.2009.169060","article-title":"Rats Selectively Bred for Low Aerobic Capacity Have Reduced Hepatic Mitochondrial Oxidative Capacity and Susceptibility to Hepatic Steatosis and Injury","volume":"587","author":"Thyfault","year":"2009","journal-title":"J. Physiol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.cmet.2015.04.004","article-title":"Adaptation of Hepatic Mitochondrial Function in Humans with Non-Alcoholic Fatty Liver Is Lost in Steatohepatitis","volume":"21","author":"Koliaki","year":"2015","journal-title":"Cell Metab."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1053\/j.gastro.2005.02.001","article-title":"Mice Heterozygous for a Defect in Mitochondrial Trifunctional Protein Develop Hepatic Steatosis and Insulin Resistance","volume":"128","author":"Ibdah","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1002\/hep.26285","article-title":"Selective Hepatic Insulin Resistance in a Murine Model Heterozygous for a Mitochondrial Trifunctional Protein Defect","volume":"57","author":"Rector","year":"2013","journal-title":"Hepatology"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1002\/hep.32324","article-title":"Compromised Hepatic Mitochondrial Fatty Acid Oxidation and Reduced Markers of Mitochondrial Turnover in Human NAFLD","volume":"76","author":"Moore","year":"2022","journal-title":"Hepatology"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"G400","DOI":"10.1152\/ajpgi.00121.2020","article-title":"Mitochondrial Oxidative Injury: A Key Player in Nonalcoholic Fatty Liver Disease","volume":"319","author":"Dornas","year":"2020","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1089\/ars.2012.4581","article-title":"Dietary (Poly)Phenolics in Human Health: Structures, Bioavailability, and Evidence of Protective Effects against Chronic Diseases","volume":"18","author":"Spencer","year":"2013","journal-title":"Antioxid. Redox Signal"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.jhep.2012.05.019","article-title":"Critical Role of Cytochrome P450 2E1 (CYP2E1) in the Development of High Fat-Induced Non-Alcoholic Steatohepatitis","volume":"57","author":"Abdelmegeed","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1002\/hep.1840380426","article-title":"Defective Hepatic Mitochondrial Respiratory Chain in Patients with Nonalcoholic Steatohepatitis","volume":"38","author":"Rubio","year":"2003","journal-title":"Hepatology"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1053\/gast.2001.23256","article-title":"Nonalcoholic Steatohepatitis: Association of Insulin Resistance and Mitochondrial Abnormalities","volume":"120","author":"Sanyal","year":"2001","journal-title":"Gastroenterology"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1126\/science.1112125","article-title":"Mitochondrial DNA Mutations, Oxidative Stress, and Apoptosis in Mammalian Aging","volume":"309","author":"Kujoth","year":"2005","journal-title":"Science"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1093\/nar\/gkp100","article-title":"Oxidative Stress Induces Degradation of Mitochondrial DNA","volume":"37","author":"Shokolenko","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Auger, C., Alhasawi, A., Contavadoo, M., and Appanna, V.D. (2015). Dysfunctional Mitochondrial Bioenergetics and the Pathogenesis of Hepatic Disorders. Front. Cell Dev. Biol., 3.","DOI":"10.3389\/fcell.2015.00040"},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Malik, A.N., Sim\u00f5es, I.C.M., Rosa, H.S., Khan, S., Karkucinska-Wieckowska, A., and Wieckowski, M.R. (2019). A Diet Induced Maladaptive Increase in Hepatic Mitochondrial DNA Precedes OXPHOS Defects and May Contribute to Non-Alcoholic Fatty Liver Disease. Cells, 8.","DOI":"10.3390\/cells8101222"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"S20","DOI":"10.1111\/j.1440-1746.2006.04640.x","article-title":"Role of Mitochondria in Non-Alcoholic Fatty Liver Disease","volume":"22","author":"Pessayre","year":"2007","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"G193","DOI":"10.1152\/ajpgi.00426.2001","article-title":"Nonalcoholic Steatosis and Steatohepatitis. V. Mitochondrial Dysfunction in Steatohepatitis","volume":"282","author":"Pessayre","year":"2002","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/hep.20283","article-title":"Free Fatty Acids Promote Hepatic Lipotoxicity by Stimulating TNF-Alpha Expression via a Lysosomal Pathway","volume":"40","author":"Feldstein","year":"2004","journal-title":"Hepatology"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1055\/s-0030-1267539","article-title":"Novel Insights into the Pathophysiology of Nonalcoholic Fatty Liver Disease","volume":"30","author":"Feldstein","year":"2010","journal-title":"Semin. Liver Dis."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1089\/ars.2012.5149","article-title":"Reactive Oxygen Species in Inflammation and Tissue Injury","volume":"20","author":"Mittal","year":"2014","journal-title":"Antioxid. Redox Signal"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1111\/jnc.13008","article-title":"Rapid Mitochondrial Dysfunction Mediates TNF-Alpha-Induced Neurotoxicity","volume":"132","author":"Doll","year":"2015","journal-title":"J. Neurochem."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Mihm, S. (2018). Danger-Associated Molecular Patterns (DAMPs): Molecular Triggers for Sterile Inflammation in the Liver. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19103104"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"6965","DOI":"10.3748\/wjg.v22.i31.6965","article-title":"Mitochondrial DNA from Hepatocytes as a Ligand for TLR9: Drivers of Nonalcoholic Steatohepatitis?","volume":"22","author":"Handa","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1172\/JCI83885","article-title":"Hepatocyte Mitochondrial DNA Drives Nonalcoholic Steatohepatitis by Activation of TLR9","volume":"126","author":"Santoro","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"E730","DOI":"10.1152\/ajpendo.00225.2016","article-title":"Treatment of Nonalcoholic Fatty Liver Disease: Role of AMPK","volume":"311","author":"Smith","year":"2016","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Amirkhizi, F., Taghizadeh, M., Khalese-Ranjbar, B., Hamedi-Shahraki, S., and Asghari, S. (2025). The Clinical Value of Serum Sirtuin-1 Concentration in the Diagnosis of Metabolic Dysfunction-Associated Steatotic Liver Disease. BMC Gastroenterol., 25.","DOI":"10.1186\/s12876-025-03613-8"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"10084","DOI":"10.3748\/wjg.v22.i46.10084","article-title":"Sirtuins and Nonalcoholic Fatty Liver Disease","volume":"22","author":"Nassir","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1089\/ars.2017.7172","article-title":"Dihydromyricetin Ameliorates Nonalcoholic Fatty Liver Disease by Improving Mitochondrial Respiratory Capacity and Redox Homeostasis Through Modulation of SIRT3 Signaling","volume":"30","author":"Zeng","year":"2019","journal-title":"Antioxid. Redox Signal."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1194\/jlr.M080952","article-title":"Regulation of Mitochondrial Trifunctional Protein Modulates Nonalcoholic Fatty Liver Disease in Mice","volume":"59","author":"Nassir","year":"2018","journal-title":"J. Lipid Res."},{"key":"ref_160","first-page":"190","article-title":"Role of Mitochondrial Depolarization and Disrupted Mitochondrial Homeostasis in Non-Alcoholic Steatohepatitis and Fibrosis in Mice","volume":"11","author":"Krishnasamy","year":"2019","journal-title":"Int. J. Physiol. Pathophysiol. Pharmacol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.cell.2019.04.010","article-title":"Deficient Endoplasmic Reticulum-Mitochondrial Phosphatidylserine Transfer Causes Liver Disease","volume":"177","author":"Vives","year":"2019","journal-title":"Cell"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1128\/MCB.00167-12","article-title":"BNip3 Regulates Mitochondrial Function and Lipid Metabolism in the Liver","volume":"32","author":"Glick","year":"2012","journal-title":"Mol. Cell Biol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1139\/apnm-2015-0470","article-title":"Exercise Mitigates Mitochondrial Permeability Transition Pore and Quality Control Mechanisms Alterations in Nonalcoholic Steatohepatitis","volume":"41","author":"Passos","year":"2016","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1053\/j.gastro.2012.03.003","article-title":"Intrahepatic Diacylglycerol Content Is Associated with Hepatic Insulin Resistance in Obese Subjects","volume":"142","author":"Magkos","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"203","DOI":"10.2337\/db08-1074","article-title":"Hepatic Stearoyl-CoA Desaturase (SCD)-1 Activity and Diacylglycerol but Not Ceramide Concentrations Are Increased in the Nonalcoholic Human Fatty Liver","volume":"58","author":"Kotronen","year":"2009","journal-title":"Diabetes"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"16381","DOI":"10.1073\/pnas.1113359108","article-title":"Cellular Mechanism of Insulin Resistance in Nonalcoholic Fatty Liver Disease","volume":"108","author":"Kumashiro","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"2741","DOI":"10.1007\/s00125-012-2649-3","article-title":"Regulation of Plasma Ceramide Levels with Fatty Acid Oversupply: Evidence That the Liver Detects and Secretes de Novo Synthesised Ceramide","volume":"55","author":"Watt","year":"2012","journal-title":"Diabetologia"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/j.cmet.2017.02.010","article-title":"Ceramide Is Metabolized to Acylceramide and Stored in Lipid Droplets","volume":"25","author":"Senkal","year":"2017","journal-title":"Cell Metab."},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Hajduch, E., Lachkar, F., Ferr\u00e9, P., and Foufelle, F. (2021). Roles of Ceramides in Non-Alcoholic Fatty Liver Disease. J. Clin. Med., 10.","DOI":"10.3390\/jcm10040792"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"715","DOI":"10.3233\/JAD-2009-0984","article-title":"Hepatic Ceramide May Mediate Brain Insulin Resistance and Neurodegeneration in Type 2 Diabetes and Non-Alcoholic Steatohepatitis","volume":"16","author":"Lawton","year":"2009","journal-title":"J. Alzheimers Dis."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.jhep.2014.09.023","article-title":"Acid Sphingomyelinase-Ceramide System in Steatohepatitis: A Novel Target Regulating Multiple Pathways","volume":"62","author":"Mato","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1194\/jlr.P056002","article-title":"Biomarkers of NAFLD Progression: A Lipidomics Approach to an Epidemic","volume":"56","author":"Gorden","year":"2015","journal-title":"J. Lipid Res."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.2337\/dc17-1318","article-title":"Specific Hepatic Sphingolipids Relate to Insulin Resistance, Oxidative Stress, and Inflammation in Nonalcoholic Steatohepatitis","volume":"41","author":"Apostolopoulou","year":"2018","journal-title":"Diabetes Care"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/j.jhep.2016.01.002","article-title":"Hepatic Ceramides Dissociate Steatosis and Insulin Resistance in Patients with Non-Alcoholic Fatty Liver Disease","volume":"64","author":"Luukkonen","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"100154","DOI":"10.1016\/j.xcrm.2020.100154","article-title":"Dihydroceramides in Triglyceride-Enriched VLDL Are Associated with Nonalcoholic Fatty Liver Disease Severity in Type 2 Diabetes","volume":"1","author":"Carlier","year":"2020","journal-title":"Cell Rep. Med."},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Bandet, C.L., Tan-Chen, S., Bourron, O., Le Stunff, H., and Hajduch, E. (2019). Sphingolipid Metabolism: New Insight into Ceramide-Induced Lipotoxicity in Muscle Cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030479"},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Li, Y., Talbot, C.L., and Chaurasia, B. (2020). Ceramides in Adipose Tissue. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00407"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.febslet.2010.12.022","article-title":"Protein Kinase C Isoforms: Mediators of Reactive Lipid Metabolites in the Development of Insulin Resistance","volume":"585","author":"Turban","year":"2011","journal-title":"FEBS Lett."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"600","DOI":"10.2337\/db09-0897","article-title":"Plasma Membrane Subdomain Compartmentalization Contributes to Distinct Mechanisms of Ceramide Action on Insulin Signaling","volume":"59","author":"Blouin","year":"2010","journal-title":"Diabetes"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"7794","DOI":"10.1128\/MCB.23.21.7794-7808.2003","article-title":"Ceramide Disables 3-Phosphoinositide Binding to the Pleckstrin Homology Domain of Protein Kinase B (PKB)\/Akt by a PKCzeta-Dependent Mechanism","volume":"23","author":"Powell","year":"2003","journal-title":"Mol. Cell Biol."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"12450","DOI":"10.1074\/jbc.M700082200","article-title":"Ceramide Recruits and Activates Protein Kinase C Zeta (PKC Zeta) within Structured Membrane Microdomains","volume":"282","author":"Fox","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1002\/hep.26606","article-title":"Hepatic Cannabinoid-1 Receptors Mediate Diet-Induced Insulin Resistance by Increasingde Novosynthesis of Long-Chain Ceramides","volume":"59","author":"Cinar","year":"2014","journal-title":"Hepatology"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.2337\/diabetes.50.10.2210","article-title":"A Role for Protein Phosphatase 2A-like Activity, but Not Atypical Protein Kinase Czeta, in the Inhibition of Protein Kinase B\/Akt and Glycogen Synthesis by Palmitate","volume":"50","author":"Cazzolli","year":"2001","journal-title":"Diabetes"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.cmet.2014.09.015","article-title":"CerS2 Haploinsufficiency Inhibits \u03b2-Oxidation and Confers Susceptibility to Diet-Induced Steatohepatitis and Insulin Resistance","volume":"20","author":"Raichur","year":"2014","journal-title":"Cell Metab."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1002\/hep.26015","article-title":"Ablation of Very Long Acyl Chain Sphingolipids Causes Hepatic Insulin Resistance in Mice Due to Altered Detergent-Resistant Membranes","volume":"57","author":"Park","year":"2013","journal-title":"Hepatology"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"10911","DOI":"10.1074\/jbc.M109.077610","article-title":"A Critical Role for Ceramide Synthase 2 in Liver Homeostasis: II. Insights into Molecular Changes Leading to Hepatopathy","volume":"285","author":"Brenner","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1054\/clnu.2001.0529","article-title":"Plasma Total and Free Fatty Acids Composition in Human Non-Alcoholic Steatohepatitis","volume":"21","author":"Fidalgo","year":"2002","journal-title":"Clin. Nutr."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1007\/s00535-013-0758-5","article-title":"Mechanisms of Hepatic Triglyceride Accumulation in Non-Alcoholic Fatty Liver Disease","volume":"48","author":"Kawano","year":"2013","journal-title":"J. Gastroenterol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.cmet.2015.06.007","article-title":"Targeted Induction of Ceramide Degradation Leads to Improved Systemic Metabolism and Reduced Hepatic Steatosis","volume":"22","author":"Xia","year":"2015","journal-title":"Cell Metab."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S1097-2765(05)00010-9","article-title":"Decreased IRS-2 and Increased SREBP-1c Lead to Mixed Insulin Resistance and Sensitivity in Livers of Lipodystrophic and Ob\/Ob Mice","volume":"6","author":"Shimomura","year":"2000","journal-title":"Mol. Cell"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1172\/JCI37007","article-title":"GRP78 Expression Inhibits Insulin and ER Stress-Induced SREBP-1c Activation and Reduces Hepatic Steatosis in Mice","volume":"119","author":"Kammoun","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1007\/s12072-010-9202-6","article-title":"Effects of Nuclear Receptor FXR on the Regulation of Liver Lipid Metabolism in Patients with Non-Alcoholic Fatty Liver Disease","volume":"4","author":"Yang","year":"2010","journal-title":"Hepatol. Int."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1210\/jc.2010-2129","article-title":"Up-Regulation of PPAR-Gamma mRNA Expression in the Liver of Obese Patients: An Additional Reinforcing Lipogenic Mechanism to SREBP-1c Induction","volume":"96","author":"Pettinelli","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"22173","DOI":"10.3390\/ijms151222173","article-title":"Altered Fatty Acid Metabolism-Related Gene Expression in Liver from Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease","volume":"15","author":"Auguet","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1161\/01.atv.0000125703.20434.4d","article-title":"Ceramide Synthesis Correlates with the Posttranscriptional Regulation of the Sterol-Regulatory Element-Binding Protein","volume":"24","author":"Worgall","year":"2004","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.cmet.2006.04.005","article-title":"Divergent Regulation of Hepatic Glucose and Lipid Metabolism by Phosphoinositide 3-Kinase via Akt and PKClambda\/Zeta","volume":"3","author":"Taniguchi","year":"2006","journal-title":"Cell Metab."},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"Sokolowska, E., and Blachnio-Zabielska, A. (2019). The Role of Ceramides in Insulin Resistance. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00577"},{"key":"ref_198","doi-asserted-by":"crossref","unstructured":"Chen, J.Y., Newcomb, B., Zhou, C., Pondick, J.V., Ghoshal, S., York, S.R., Motola, D.L., Coant, N., Yi, J.K., and Mao, C. (2017). Tricyclic Antidepressants Promote Ceramide Accumulation to Regulate Collagen Production in Human Hepatic Stellate Cells. Sci. Rep., 7.","DOI":"10.1038\/srep44867"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1002\/hep.22753","article-title":"Cathepsins B and D Drive Hepatic Stellate Cell Proliferation and Promote Their Fibrogenic Potential","volume":"49","author":"Moles","year":"2009","journal-title":"Hepatology"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"eaay8798","DOI":"10.1126\/scitranslmed.aay8798","article-title":"Targeting Acid Ceramidase Inhibits YAP\/TAZ Signaling to Reduce Fibrosis in Mice","volume":"12","author":"Alsamman","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_201","doi-asserted-by":"crossref","unstructured":"Clemente-Su\u00e1rez, V.J., Beltr\u00e1n-Velasco, A.I., Redondo-Fl\u00f3rez, L., Mart\u00edn-Rodr\u00edguez, A., and Tornero-Aguilera, J.F. (2023). Global Impacts of Western Diet and Its Effects on Metabolism and Health: A Narrative Review. Nutrients, 15.","DOI":"10.3390\/nu15122749"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1002\/hep.23535","article-title":"Network, for the N.S.C.R. Increased Fructose Consumption Is Associated with Fibrosis Severity in Patients with Nonalcoholic Fatty Liver Disease","volume":"51","author":"Abdelmalek","year":"2010","journal-title":"Hepatology"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.jhep.2018.01.019","article-title":"Fructose and Sugar: A Major Mediator of Non-Alcoholic Fatty Liver Disease","volume":"68","author":"Jensen","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1053\/j.gastro.2015.04.005","article-title":"Weight Loss Through Lifestyle Modification Significantly Reduces Features of Nonalcoholic Steatohepatitis","volume":"149","author":"Friedman","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.jhep.2024.04.031","article-title":"EASL\u2013EASD\u2013EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)","volume":"81","author":"Tacke","year":"2024","journal-title":"J. Hepatol."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1007\/s00125-011-2065-0","article-title":"Effects of Weight Loss and Exercise on Insulin Resistance, and Intramyocellular Triacylglycerol, Diacylglycerol and Ceramide","volume":"54","author":"Amati","year":"2011","journal-title":"Diabetologia"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"74","DOI":"10.2337\/db15-0675","article-title":"Mechanism by Which Caloric Restriction Improves Insulin Sensitivity in Sedentary Obese Adults","volume":"65","author":"Johnson","year":"2016","journal-title":"Diabetes"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"4462","DOI":"10.3748\/wjg.14.4462","article-title":"Metabolomic Changes in Fatty Liver Can Be Modified by Dietary Protein and Calcium during Energy Restriction","volume":"14","author":"Pilvi","year":"2008","journal-title":"World J. Gastroenterol."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1007\/s12265-013-9453-4","article-title":"Beneficial Cardiac Effects of Caloric Restriction Are Lost with Age in a Murine Model of Obesity","volume":"6","author":"AlGhatrif","year":"2013","journal-title":"J. Cardiovasc. Transl. Res."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s13105-021-00863-4","article-title":"Calorie Restriction Changes Lipidomic Profiles and Maintains Mitochondrial Function and Redox Balance during Isoproterenol-Induced Cardiac Hypertrophy","volume":"78","author":"David","year":"2022","journal-title":"J. Physiol. Biochem."},{"key":"ref_211","doi-asserted-by":"crossref","unstructured":"Civitarese, A.E., Carling, S., Heilbronn, L.K., Hulver, M.H., Ukropcova, B., Deutsch, W.A., Smith, S.R., and Ravussin, E. (2007). CALERIE Pennington Team Calorie Restriction Increases Muscle Mitochondrial Biogenesis in Healthy Humans. PLoS Med., 4.","DOI":"10.1371\/journal.pmed.0040076"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1126\/science.285.5432.1390","article-title":"Gene Expression Profile of Aging and Its Retardation by Caloric Restriction","volume":"285","author":"Lee","year":"1999","journal-title":"Science"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.cmet.2010.11.015","article-title":"Calorie Restriction Reduces Oxidative Stress by SIRT3-Mediated SOD2 Activation","volume":"12","author":"Qiu","year":"2010","journal-title":"Cell Metab."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.cct.2018.03.014","article-title":"Effectiveness of a Carbohydrate Restricted Diet to Treat Non-Alcoholic Fatty Liver Disease in Adolescents with Obesity: Trial Design and Methodology","volume":"68","author":"Dowla","year":"2018","journal-title":"Contemp. Clin. Trials"},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1111\/j.1440-1746.2006.04548.x","article-title":"Restriction of Dietary Calories, Fat and Iron Improves Non-Alcoholic Fatty Liver Disease","volume":"22","author":"Yamamoto","year":"2007","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_216","doi-asserted-by":"crossref","unstructured":"Varkaneh, H.K., Poursoleiman, F., Al Masri, M.K., Alras, K.A., Shayah, Y., Masmoum, M.D., Alangari, F.A., Alras, A.A., Rinaldi, G., and Day, A.S. (2022). Low Fat Diet versus Low Carbohydrate Diet for Management of Non-Alcohol Fatty Liver Disease: A Systematic Review. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.987921"},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"3786","DOI":"10.2337\/dc13-0102","article-title":"Long-Lasting Improvements in Liver Fat and Metabolism Despite Body Weight Regain After Dietary Weight Loss","volume":"36","author":"Haufe","year":"2013","journal-title":"Diabetes Care"},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1111\/liv.14360","article-title":"The Role of Nutrition in Non-Alcoholic Fatty Liver Disease: Pathophysiology and Management","volume":"40","year":"2020","journal-title":"Liver Int."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1097\/HEP.0000000000000323","article-title":"AASLD Practice Guidance on the Clinical Assessment and Management of Nonalcoholic Fatty Liver Disease","volume":"77","author":"Rinella","year":"2023","journal-title":"Hepatology"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/978-1-0716-1433-4_12","article-title":"Protocols for Mitochondria as the Target of Pharmacological Therapy in the Context of Nonalcoholic Fatty Liver Disease (NAFLD)","volume":"2310","author":"Grattagliano","year":"2021","journal-title":"Methods Mol. Biol."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"206","DOI":"10.2741\/4892","article-title":"Current Treatment Paradigms and Emerging Therapies for NAFLD\/NASH","volume":"26","author":"Raza","year":"2021","journal-title":"Front. Biosci. (Landmark Ed)"},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"101122","DOI":"10.1016\/j.molmet.2020.101122","article-title":"Nonalcoholic Fatty Liver Disease (NAFLD) from Pathogenesis to Treatment Concepts in Humans","volume":"50","author":"Pafili","year":"2021","journal-title":"Mol. Metab."},{"key":"ref_223","doi-asserted-by":"crossref","unstructured":"Serrano, J.C.E., Cassanye, A., Mart\u00edn-Gari, M., Granado-Serrano, A.B., and Portero-Ot\u00edn, M. (2016). Effect of Dietary Bioactive Compounds on Mitochondrial and Metabolic Flexibility. Diseases, 4.","DOI":"10.3390\/diseases4010014"},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"107324","DOI":"10.1016\/j.phrs.2024.107324","article-title":"The Role of Polyphenols in Modulating Mitophagy: Implications for Therapeutic Interventions","volume":"207","author":"Lin","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.freeradbiomed.2013.11.029","article-title":"Hydroxytyrosol Prevents Diet-Induced Metabolic Syndrome and Attenuates Mitochondrial Abnormalities in Obese Mice","volume":"67","author":"Cao","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jnutbio.2017.06.011","article-title":"Ferulic Acid, a Bioactive Component of Rice Bran, Improves Oxidative Stress and Mitochondrial Biogenesis and Dynamics in Mice and in Human Mononuclear Cells","volume":"48","author":"Werner","year":"2017","journal-title":"J. Nutr. Biochem."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.2337\/db16-0924","article-title":"Butyrate Regulates Liver Mitochondrial Function, Efficiency, and Dynamics in Insulin-Resistant Obese Mice","volume":"66","author":"Mollica","year":"2017","journal-title":"Diabetes"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"e34","DOI":"10.1056\/NEJMoa1800389","article-title":"Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts","volume":"378","author":"Estruch","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1161\/CIRCULATIONAHA.116.024261","article-title":"Plasma Ceramides, Mediterranean Diet, and Incident Cardiovascular Disease in the PREDIMED Trial (Prevenci\u00f3n Con Dieta Mediterr\u00e1nea)","volume":"135","author":"Wang","year":"2017","journal-title":"Circulation"},{"key":"ref_230","doi-asserted-by":"crossref","unstructured":"Daidone, M., Casuccio, A., Puleo, M.G., Cuore, A.D., Pacinella, G., Chiara, T.D., Raimondo, D.D., Immordino, P., and Tuttolomondo, A. (2024). Mediterranean Diet Effects on Vascular Health and Serum Levels of Adipokines and Ceramides. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0300844"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.abb.2003.08.020","article-title":"Characterizing the Effects of Saturated Fatty Acids on Insulin Signaling and Ceramide and Diacylglycerol Accumulation in 3T3-L1 Adipocytes and C2C12 Myotubes","volume":"419","author":"Chavez","year":"2003","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"24202","DOI":"10.1074\/jbc.274.34.24202","article-title":"Ceramide Generation Is Sufficient to Account for the Inhibition of the Insulin-Stimulated PKB Pathway in C2C12 Skeletal Muscle Cells Pretreated with Palmitate","volume":"274","author":"Craig","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1016\/S0006-291X(03)00449-2","article-title":"Saturated Free Fatty Acids, Palmitic Acid and Stearic Acid, Induce Apoptosis by Stimulation of Ceramide Generation in Rat Testicular Leydig Cell","volume":"303","author":"Lu","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"2086","DOI":"10.1111\/dom.13773","article-title":"Mechanisms Underlying the Cardiometabolic Protective Effect of Walnut Consumption in Obese People: A Cross-over, Randomized, Double-Blind, Controlled Inpatient Physiology Study","volume":"21","author":"Tuccinardi","year":"2019","journal-title":"Diabetes Obes. Metab."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.3945\/ajcn.2008.26528","article-title":"Association between Adherence to the Mediterranean Diet and Oxidative Stress","volume":"88","author":"Dai","year":"2008","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.maturitas.2011.06.003","article-title":"Long-Term Adherence to the Mediterranean Diet Reduces the Prevalence of Hyperuricaemia in Elderly Individuals, without Known Cardiovascular Disease: The Ikaria Study","volume":"70","author":"Chrysohoou","year":"2011","journal-title":"Maturitas"},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1016\/j.jacc.2010.09.073","article-title":"The Effect of Mediterranean Diet on Metabolic Syndrome and Its Components: A Meta-Analysis of 50 Studies and 534,906 Individuals","volume":"57","author":"Kastorini","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"248","DOI":"10.3945\/ajcn.2008.26094","article-title":"Inhibition of Circulating Immune Cell Activation: A Molecular Antiinflammatory Effect of the Mediterranean Diet","volume":"89","author":"Mena","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1001\/jama.292.12.1440","article-title":"Effect of a Mediterranean-Style Diet on Endothelial Dysfunction and Markers of Vascular Inflammation in the Metabolic Syndrome: A Randomized Trial","volume":"292","author":"Esposito","year":"2004","journal-title":"JAMA"},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.3945\/jn.111.148726","article-title":"The Mediterranean Diet Pattern and Its Main Components Are Associated with Lower Plasma Concentrations of Tumor Necrosis Factor Receptor 60 in Patients at High Risk for Cardiovascular Disease","volume":"142","author":"Casas","year":"2012","journal-title":"J. Nutr."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.jacc.2004.03.039","article-title":"Adherence to the Mediterranean Diet Attenuates Inflammation and Coagulation Process in Healthy Adults: The ATTICA Study","volume":"44","author":"Chrysohoou","year":"2004","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.clnu.2013.08.014","article-title":"Adherence to the Mediterranean Diet Is Associated with the Severity of Non-Alcoholic Fatty Liver Disease","volume":"33","author":"Kontogianni","year":"2014","journal-title":"Clin. Nutr."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1017\/S000711451800137X","article-title":"Improvements in Clinical Characteristics of Patients with Non-Alcoholic Fatty Liver Disease, after an Intervention Based on the Mediterranean Lifestyle: A Randomised Controlled Clinical Trial","volume":"120","author":"Katsagoni","year":"2018","journal-title":"Br. J. Nutr."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"3150","DOI":"10.3748\/wjg.v23.i17.3150","article-title":"Effect of a Counseling-Supported Treatment with the Mediterranean Diet and Physical Activity on the Severity of the Non-Alcoholic Fatty Liver Disease","volume":"23","author":"Gelli","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.jhep.2019.04.013","article-title":"The Beneficial Effects of Mediterranean Diet over Low-Fat Diet May Be Mediated by Decreasing Hepatic Fat Content","volume":"71","author":"Gepner","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_246","doi-asserted-by":"crossref","unstructured":"Giordano, C., Marchi\u00f2, M., Timofeeva, E., and Biagini, G. (2014). Neuroactive Peptides as Putative Mediators of Antiepileptic Ketogenic Diets. Front. Neurol., 5.","DOI":"10.3389\/fneur.2014.00063"},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.seizure.2005.11.008","article-title":"Serum Ghrelin Levels Are Enhanced in Patients with Epilepsy","volume":"15","author":"Berilgen","year":"2006","journal-title":"Seizure"},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"100256","DOI":"10.1016\/j.jhepr.2021.100256","article-title":"Treatment of NAFLD with Intermittent Calorie Restriction or Low-Carb High-Fat Diet\u2014A Randomised Controlled Trial","volume":"3","author":"Holmer","year":"2021","journal-title":"JHEP Rep."},{"key":"ref_249","doi-asserted-by":"crossref","unstructured":"Cunha, G.M., Guzman, G., De Mello, L.L.C., Trein, B., Spina, L., Bussade, I., Marques Prata, J., Sajoux, I., and Countinho, W. (2020). Efficacy of a 2-Month Very Low-Calorie Ketogenic Diet (VLCKD) Compared to a Standard Low-Calorie Diet in Reducing Visceral and Liver Fat Accumulation in Patients With Obesity. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00607"},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1002\/oby.22468","article-title":"Glucose and Lipid Homeostasis and Inflammation in Humans Following an Isocaloric Ketogenic Diet","volume":"27","author":"Rosenbaum","year":"2019","journal-title":"Obesity"},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"e70099","DOI":"10.1002\/jgh3.70099","article-title":"Effect of a Ketogenic Diet on Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Progression: A Randomized Controlled Trial","volume":"9","author":"Chirapongsathorn","year":"2025","journal-title":"JGH Open"},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"4137","DOI":"10.1113\/JP283552","article-title":"The Ketogenic Diet Prevents Steatosis and Insulin Resistance by Reducing Lipogenesis, Diacylglycerol Accumulation and Protein Kinase C Activity in Male Rat Liver","volume":"600","author":"Jani","year":"2022","journal-title":"J. Physiol."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"7347","DOI":"10.1073\/pnas.1922344117","article-title":"Effect of a Ketogenic Diet on Hepatic Steatosis and Hepatic Mitochondrial Metabolism in Nonalcoholic Fatty Liver Disease","volume":"117","author":"Luukkonen","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1007\/s11064-018-2588-6","article-title":"A Ketogenic Diet Improves Mitochondrial Biogenesis and Bioenergetics via the PGC1\u03b1-SIRT3-UCP2 Axis","volume":"44","author":"Lauritzen","year":"2019","journal-title":"Neurochem. Res."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"e95","DOI":"10.1111\/epi.13038","article-title":"Ketogenic Diet Exhibits Anti-Inflammatory Properties","volume":"56","author":"Dupuis","year":"2015","journal-title":"Epilepsia"},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.diabet.2015.09.001","article-title":"Coffee Consumption and Risk of the Metabolic Syndrome: A Meta-Analysis","volume":"42","author":"Shang","year":"2016","journal-title":"Diabetes Metab."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1111\/liv.12379","article-title":"Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Coffee Consumption in NAFLD Patients with Lower Insulin Resistance Is Associated with Lower Risk of Severe Fibrosis","volume":"34","author":"Bambha","year":"2014","journal-title":"Liver Int."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1056\/NEJMra1816604","article-title":"Coffee, Caffeine, and Health","volume":"383","author":"Hu","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_259","doi-asserted-by":"crossref","unstructured":"Lee, J.-H., Park, J., and Ahn, S.B. (2023). Different Associations of Coffee Consumption with the Risk of Incident Metabolic Dysfunction-Associated Steatotic Liver Disease and Advanced Liver Fibrosis. Nutrients, 16.","DOI":"10.3390\/nu16010140"},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nut.2016.12.021","article-title":"Coffee Consumption in Aged Mice Increases Energy Production and Decreases Hepatic mTOR Levels","volume":"38","author":"Takahashi","year":"2017","journal-title":"Nutrition"},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"e2000527","DOI":"10.1002\/mnfr.202000527","article-title":"Coffee, Black Tea, and Green Tea Consumption in Relation to Plasma Metabolites in an Asian Population","volume":"64","author":"Seow","year":"2020","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1038\/s41467-022-28496-1","article-title":"Dihydroceramide- and Ceramide-Profiling Provides Insights into Human Cardiometabolic Disease Etiology","volume":"13","author":"Wittenbecher","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1007\/s11095-014-1526-9","article-title":"Chlorogenic Acid Improves High Fat Diet-Induced Hepatic Steatosis and Insulin Resistance in Mice","volume":"32","author":"Ma","year":"2015","journal-title":"Pharm. Res."},{"key":"ref_264","doi-asserted-by":"crossref","unstructured":"Salomone, F., Galvano, F., and Li Volti, G. (2017). Molecular Bases Underlying the Hepatoprotective Effects of Coffee. Nutrients, 9.","DOI":"10.3390\/nu9010085"},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"E122","DOI":"10.1152\/ajpendo.00441.2010","article-title":"Coffee Polyphenols Suppress Diet-Induced Body Fat Accumulation by Downregulating SREBP-1c and Related Molecules in C57BL\/6J Mice","volume":"300","author":"Murase","year":"2011","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1016\/j.bcp.2013.02.008","article-title":"Anti-Diabetic and Anti-Lipidemic Effects of Chlorogenic Acid Are Mediated by Ampk Activation","volume":"85","author":"Ong","year":"2013","journal-title":"Biochem. Pharmacol."},{"key":"ref_267","first-page":"241","article-title":"Short Term Effects of Coffee Components Consumption on Gut Microbiota in Patients with Non-Alcoholic Fatty Liver and Diabetes: A Pilot Randomized Placebo-Controlled, Clinical Trial","volume":"19","author":"Mansour","year":"2020","journal-title":"EXCLI J."},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1007\/s00011-013-0610-7","article-title":"Effect of Chlorogenic Acid on LPS-Induced Proinflammatory Signaling in Hepatic Stellate Cells","volume":"62","author":"Shi","year":"2013","journal-title":"Inflamm. Res."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3727\/105221617X15124844266408","article-title":"The Effects of Physical Exercise on Fatty Liver Disease","volume":"18","author":"Sud","year":"2018","journal-title":"Gene Expr."},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1080\/17461391.2019.1571114","article-title":"Mechanisms of Beneficial Effects of Exercise Training on Non-Alcoholic Fatty Liver Disease (NAFLD): Roles of Oxidative Stress and Inflammation","volume":"19","author":"Farzanegi","year":"2019","journal-title":"Eur. J. Sport Sci."},{"key":"ref_271","first-page":"1","article-title":"Physical Exercise and Liver \u201cFitness\u201d: Role of Mitochondrial Function and Epigenetics-Related Mechanisms in Non-Alcoholic Fatty Liver Disease","volume":"32","author":"Beleza","year":"2019","journal-title":"Mol. Metab."},{"key":"ref_272","doi-asserted-by":"crossref","unstructured":"Collado-Mateo, D., Lav\u00edn-P\u00e9rez, A.M., Pe\u00f1acoba, C., Del Coso, J., Leyton-Rom\u00e1n, M., Luque-Casado, A., Gasque, P., Fern\u00e1ndez-del-Olmo, M.\u00c1., and Amado-Alonso, D. (2021). Key Factors Associated with Adherence to Physical Exercise in Patients with Chronic Diseases and Older Adults: An Umbrella Review. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18042023"},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"e011939","DOI":"10.1136\/bmjopen-2016-011939","article-title":"Associations between Sitting Time and Non-Alcoholic Fatty Liver Diseases in Chinese Male Workers: A Cross-Sectional Study","volume":"6","author":"Wei","year":"2016","journal-title":"BMJ Open"},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1136\/flgastro-2014-100432","article-title":"Non-Alcoholic Fatty Liver Disease Is Associated with Higher Levels of Objectively Measured Sedentary Behaviour and Lower Levels of Physical Activity than Matched Healthy Controls","volume":"6","author":"Hallsworth","year":"2015","journal-title":"Frontline Gastroenterol."},{"key":"ref_275","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1111\/apt.12038","article-title":"Non-Alcoholic Fatty Liver Disease (NAFLD) Is Associated with Low Level of Physical Activity: A Population-Based Study","volume":"36","author":"Gerber","year":"2012","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1111\/liv.12552","article-title":"Role of Physical Activity in Nonalcoholic Fatty Liver Disease in Terms of Visceral Obesity and Insulin Resistance","volume":"35","author":"Kwak","year":"2015","journal-title":"Liver Int."},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1002\/hep.22525","article-title":"Role of Leisure-Time Physical Activity in Nonalcoholic Fatty Liver Disease: A Population-Based Study","volume":"48","author":"Goldsmith","year":"2008","journal-title":"Hepatology"},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.14309\/ajg.0000000000002098","article-title":"Exercise Training Is Associated With Treatment Response in Liver Fat Content by Magnetic Resonance Imaging Independent of Clinically Significant Body Weight Loss in Patients With Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis","volume":"118","author":"Stine","year":"2023","journal-title":"Am. J. Gastroenterol."},{"key":"ref_279","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1042\/CS20150447","article-title":"Dissociation between Exercise-Induced Reduction in Liver Fat and Changes in Hepatic and Peripheral Glucose Homoeostasis in Obese Patients with Non-Alcoholic Fatty Liver Disease","volume":"130","author":"Cuthbertson","year":"2015","journal-title":"Clin. Sci."},{"key":"ref_280","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1002\/hep.25548","article-title":"Randomized Trial of Exercise Effect on Intrahepatic Triglyceride Content and Lipid Kinetics in Nonalcoholic Fatty Liver Disease","volume":"55","author":"Sullivan","year":"2012","journal-title":"Hepatology"},{"key":"ref_281","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/oby.2009.274","article-title":"A 12-Week Aerobic Exercise Program Reduces Hepatic Fat Accumulation and Insulin Resistance in Obese, Hispanic Adolescents","volume":"18","author":"Wang","year":"2010","journal-title":"Obesity"},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1136\/gut.2011.242073","article-title":"Resistance Exercise Reduces Liver Fat and Its Mediators in Non-Alcoholic Fatty Liver Disease Independent of Weight Loss","volume":"60","author":"Hallsworth","year":"2011","journal-title":"Gut"},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.metabol.2017.08.012","article-title":"Energy-Matched Moderate and High Intensity Exercise Training Improves Nonalcoholic Fatty Liver Disease Risk Independent of Changes in Body Mass or Abdominal Adiposity\u2014A Randomized Trial","volume":"78","author":"Winn","year":"2018","journal-title":"Metabolism"},{"key":"ref_284","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1007\/s10620-022-07779-z","article-title":"High-Intensity Interval Training Is Safe, Feasible and Efficacious in Nonalcoholic Steatohepatitis: A Randomized Controlled Trial","volume":"68","author":"Keating","year":"2023","journal-title":"Dig. Dis. Sci."},{"key":"ref_285","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1210\/clinem\/dgab795","article-title":"The Effect of High-Intensity Interval Training vs Moderate-Intensity Continuous Training on Liver Fat: A Systematic Review and Meta-Analysis","volume":"107","author":"Sabag","year":"2022","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_286","doi-asserted-by":"crossref","first-page":"e14918","DOI":"10.1097\/MD.0000000000014918","article-title":"A Randomized Controlled Trial on the Effectiveness of 8-Week High-Intensity Interval Exercise on Intrahepatic Triglycerides, Visceral Lipids, and Health-Related Quality of Life in Diabetic Obese Patients with Nonalcoholic Fatty Liver Disease","volume":"98","author":"Abdelbasset","year":"2019","journal-title":"Medicine"},{"key":"ref_287","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.jhep.2015.02.022","article-title":"Effect of Aerobic Exercise Training Dose on Liver Fat and Visceral Adiposity","volume":"63","author":"Keating","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.mito.2012.10.007","article-title":"Endurance Training and Chronic Intermittent Hypoxia Modulate in Vitro Salicylate-Induced Hepatic Mitochondrial Dysfunction","volume":"12","author":"Machado","year":"2012","journal-title":"Mitochondrion"},{"key":"ref_289","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1249\/MSS.0000000000000223","article-title":"Impact of Various Exercise Modalities on Hepatic Mitochondrial Function","volume":"46","author":"Fletcher","year":"2014","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_290","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.lfs.2009.11.003","article-title":"Endurance Exercise Causes Mitochondrial and Oxidative Stress in Rat Liver: Effects of a Combination of Mitochondrial Targeting Nutrients","volume":"86","author":"Sun","year":"2010","journal-title":"Life Sci."},{"key":"ref_291","doi-asserted-by":"crossref","unstructured":"Lima, F.D., Stamm, D.N., Della-Pace, I.D., Dobrachinski, F., de Carvalho, N.R., Royes, L.F.F., Soares, F.A., Rocha, J.B., Gonz\u00e1lez-Gallego, J., and Bresciani, G. (2013). Swimming Training Induces Liver Mitochondrial Adaptations to Oxidative Stress in Rats Submitted to Repeated Exhaustive Swimming Bouts. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0055668"},{"key":"ref_292","doi-asserted-by":"crossref","first-page":"E300","DOI":"10.1152\/ajpendo.00427.2013","article-title":"Combining Metformin and Aerobic Exercise Training in the Treatment of Type 2 Diabetes and NAFLD in OLETF Rats","volume":"306","author":"Linden","year":"2014","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_293","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1113\/jphysiol.2002.034850","article-title":"Exercise Induces Transient Transcriptional Activation of the PGC-1\u03b1 Gene in Human Skeletal Muscle","volume":"546","author":"Pilegaard","year":"2003","journal-title":"J. Physiol."},{"key":"ref_294","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1152\/japplphysiol.00820.2018","article-title":"Low-Intensity Exercise Induces Acute Shifts in Liver and Skeletal Muscle Substrate Metabolism but Not Chronic Adaptations in Tissue Oxidative Capacity","volume":"127","author":"Fuller","year":"2019","journal-title":"J. Appl. Physiol."},{"key":"ref_295","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1038\/labinvest.2011.55","article-title":"Fatty Liver Is Associated with Impaired Activity of PPAR\u03b3-Coactivator 1\u03b1 (PGC1\u03b1) and Mitochondrial Biogenesis in Mice","volume":"91","author":"Pen","year":"2011","journal-title":"Lab. Investig."},{"key":"ref_296","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1152\/japplphysiol.91186.2008","article-title":"Cessation of Daily Wheel Running Differentially Alters Fat Oxidation Capacity in Liver, Muscle, and Adipose Tissue","volume":"106","author":"Laye","year":"2009","journal-title":"J. Appl. Physiol."},{"key":"ref_297","doi-asserted-by":"crossref","first-page":"R1501","DOI":"10.1152\/ajpregu.00775.2010","article-title":"Role of PGC-1\u03b1 in Exercise and Fasting-Induced Adaptations in Mouse Liver","volume":"301","author":"Haase","year":"2011","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_298","doi-asserted-by":"crossref","first-page":"E1036","DOI":"10.1152\/ajpendo.00010.2016","article-title":"Loss of CTRP5 Improves Insulin Action and Hepatic Steatosis","volume":"310","author":"Lei","year":"2016","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_299","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.orcp.2017.01.004","article-title":"Aerobic Endurance Training Improves Nonalcoholic Fatty Liver Disease (NAFLD) Features via miR-33 Dependent Autophagy Induction in High Fat Diet Fed Mice","volume":"12","author":"Ghareghani","year":"2018","journal-title":"Obes. Res. Clin. Pract."},{"key":"ref_300","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1210\/me.2014-1353","article-title":"Irisin, a Novel Myokine, Regulates Glucose Uptake in Skeletal Muscle Cells via AMPK","volume":"29","author":"Lee","year":"2015","journal-title":"Mol. Endocrinol."},{"key":"ref_301","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1016\/j.cmet.2015.08.001","article-title":"Detection and Quantitation of Circulating Human Irisin by Tandem Mass Spectrometry","volume":"22","author":"Jedrychowski","year":"2015","journal-title":"Cell Metab."},{"key":"ref_302","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.2337\/diabetes.52.9.2205","article-title":"Effect of Exercise Intensity on Skeletal Muscle AMPK Signaling in Humans","volume":"52","author":"Chen","year":"2003","journal-title":"Diabetes"},{"key":"ref_303","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1111\/j.1440-1681.1997.tb02712.x","article-title":"Importance of the \u201ccrossover\u201d Concept in Exercise Metabolism","volume":"24","author":"Brooks","year":"1997","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_304","doi-asserted-by":"crossref","first-page":"e03874","DOI":"10.1016\/j.heliyon.2020.e03874","article-title":"Different Training Intensities Induced Autophagy and Histopathology Appearances Potentially Associated with Lipid Metabolism in Wistar Rat Liver","volume":"6","author":"Gunadi","year":"2020","journal-title":"Heliyon"},{"key":"ref_305","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1042\/CS20180409","article-title":"Amino Acid and Lipid Associated Plasma Metabolomic Patterns Are Related to Healthspan Indicators with Ageing","volume":"132","author":"Johnson","year":"2018","journal-title":"Clin. Sci."},{"key":"ref_306","doi-asserted-by":"crossref","first-page":"E398","DOI":"10.1152\/ajpendo.00134.2015","article-title":"Serum Sphingolipids: Relationships to Insulin Sensitivity and Changes with Exercise in Humans","volume":"309","author":"Bergman","year":"2015","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_307","doi-asserted-by":"crossref","first-page":"E99","DOI":"10.1152\/ajpendo.00587.2005","article-title":"Endurance Training in Obese Humans Improves Glucose Tolerance and Mitochondrial Fatty Acid Oxidation and Alters Muscle Lipid Content","volume":"291","author":"Bruce","year":"2006","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_308","first-page":"305","article-title":"Effect of Endurance Training on the Sphingomyelin-Signalling Pathway Activity in the Skeletal Muscles of the Rat","volume":"55","year":"2004","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_309","doi-asserted-by":"crossref","unstructured":"Reidy, P.T., Mahmassani, Z.S., McKenzie, A.I., Petrocelli, J.J., Summers, S.A., and Drummond, M.J. (2020). Influence of Exercise Training on Skeletal Muscle Insulin Resistance in Aging: Spotlight on Muscle Ceramides. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041514"},{"key":"ref_310","doi-asserted-by":"crossref","unstructured":"Gaggini, M., Vassalle, C., Carli, F., Maltinti, M., Sabatino, L., Buzzigoli, E., Mastorci, F., Sbrana, F., Gastaldelli, A., and Pingitore, A. (2021). Changes in Plasma Bioactive Lipids and Inflammatory Markers during a Half-Marathon in Trained Athletes. Appl. Sci., 11.","DOI":"10.3390\/app11104622"},{"key":"ref_311","doi-asserted-by":"crossref","first-page":"4536470","DOI":"10.1155\/2016\/4536470","article-title":"Endurance and Resistance Training Affect High Fat Diet-Induced Increase of Ceramides, Inflammasome Expression, and Systemic Inflammation in Mice","volume":"2016","author":"Mardare","year":"2016","journal-title":"J. Diabetes Res."},{"key":"ref_312","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/nrm.2017.107","article-title":"Sphingolipids and Their Metabolism in Physiology and Disease","volume":"19","author":"Hannun","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_313","doi-asserted-by":"crossref","unstructured":"American Gastroenterological Association (2002). American Gastroenterological Association Medical Position Statement: Nonalcoholic Fatty Liver Disease. Gastroenterology, 123, 1702\u20131704.","DOI":"10.1053\/gast.2002.36569"},{"key":"ref_314","doi-asserted-by":"crossref","first-page":"G874","DOI":"10.1152\/ajpgi.00510.2010","article-title":"Daily Exercise vs. Caloric Restriction for Prevention of Nonalcoholic Fatty Liver Disease in the OLETF Rat Model","volume":"300","author":"Rector","year":"2011","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_315","doi-asserted-by":"crossref","unstructured":"Wang, S.-T., Zheng, J., Peng, H.-W., Cai, X.-L., Pan, X.-T., Li, H.-Q., Hong, Q.-Z., and Peng, X.-E. (2020). Physical Activity Intervention for Non-Diabetic Patients with Non-Alcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trials. BMC Gastroenterol., 20.","DOI":"10.1186\/s12876-020-01204-3"},{"key":"ref_316","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/j.jhep.2024.06.017","article-title":"Histological Improvements Following Energy Restriction and Exercise: The Role of Insulin Resistance in Resolution of MASH","volume":"81","author":"Mucinski","year":"2024","journal-title":"J. Hepatol."},{"key":"ref_317","doi-asserted-by":"crossref","first-page":"14486","DOI":"10.1016\/S0021-9258(18)98712-0","article-title":"Inhibition of Sphingolipid Biosynthesis by Fumonisins. Implications for Diseases Associated with Fusarium Moniliforme","volume":"266","author":"Wang","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_318","first-page":"291","article-title":"Fumonisin-Induced Hepatocarcinogenesis: Mechanisms Related to Cancer Initiation and Promotion","volume":"109","author":"Gelderblom","year":"2001","journal-title":"Environ. Health Perspect."},{"key":"ref_319","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1056\/NEJMct1101691","article-title":"Fingolimod for Multiple Sclerosis","volume":"366","author":"Pelletier","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_320","doi-asserted-by":"crossref","first-page":"E1420","DOI":"10.1152\/ajpendo.00362.2009","article-title":"Long-Term Fenretinide Treatment Prevents High-Fat Diet-Induced Obesity, Insulin Resistance, and Hepatic Steatosis","volume":"297","author":"Preitner","year":"2009","journal-title":"Am. J. Physiol. Endocrinol. 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