{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:51:56Z","timestamp":1787313116400,"version":"build-2736575974"},"reference-count":128,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T00:00:00Z","timestamp":1776470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002468","name":"Dong-A University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002468","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/03qvtpc38","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Metabolic dysfunction\u2013associated steatotic liver disease (MASLD) is a systemic metabolic disorder characterized by impaired metabolic flexibility involving the liver, skeletal muscle, and adipose tissue. Although weight loss has traditionally been emphasized in its management, emerging evidence suggests that exercise exerts therapeutic effects beyond body weight reduction. This narrative review aims to examine exercise as a metabolic therapy for MASLD by integrating mechanistic insights and clinical evidence. Exercise improves hepatic steatosis, insulin resistance, mitochondrial function, and inflammatory signaling through interconnected pathways, including activation of AMPK-related signaling, enhanced fatty acid oxidation, and muscle\u2013liver crosstalk mediated by myokines. Importantly, these benefits can occur independently of weight loss, supporting a shift from weight-centered to metabolism-focused treatment strategies. Both aerobic and resistance exercise demonstrate efficacy, with combined approaches providing complementary benefits. In conclusion, exercise should be considered a central therapeutic strategy for MASLD by restoring metabolic flexibility rather than solely promoting weight reduction. Future research should focus on optimizing individualized and sustainable exercise prescriptions to enhance long-term clinical outcomes.<\/jats:p>","DOI":"10.3390\/medicina62040784","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T13:22:47Z","timestamp":1776691367000},"page":"784","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exercise as a Metabolic Therapy for MASLD: Beyond Weight Loss Toward Sustainable Exercise Strategies"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3586-1666","authenticated-orcid":false,"given":"Hee-Tae","family":"Roh","sequence":"first","affiliation":[{"name":"Department of Sports Science, College of Arts and Sports, Sun Moon University, Asan-si 31460, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4155-2250","authenticated-orcid":false,"given":"Ju-Yong","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Physical Education, College of Arts and Sports, Dong-A University, Busan 49315, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1097\/HEP.0000000000000520","article-title":"A Multisociety Delphi Consensus Statement on New Fatty Liver Disease Nomenclature","volume":"78","author":"Rinella","year":"2023","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.3350\/cmh.2024.0431","article-title":"Epidemiology of Metabolic Dysfunction-Associated Steatotic Liver Disease","volume":"31","author":"Younossi","year":"2025","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.2337\/dci24-0094","article-title":"Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in People with Diabetes: The Need for Screening and Early Intervention","volume":"48","author":"Cusi","year":"2025","journal-title":"Diabetes Care"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1001\/jama.2025.19615","article-title":"Metabolic Dysfunction-Associated Steatotic Liver Disease in Adults: A Review","volume":"335","author":"Tilg","year":"2026","journal-title":"JAMA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1053\/j.gastro.2005.04.014","article-title":"The Natural History of Nonalcoholic Fatty Liver Disease: A Population-Based Cohort Study","volume":"129","author":"Adams","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_6","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_7","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/s41591-018-0104-9","article-title":"Mechanisms of NAFLD Development and Therapeutic Strategies","volume":"24","author":"Friedman","year":"2018","journal-title":"Nat. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.cmet.2017.08.002","article-title":"Nonalcoholic Fatty Liver Disease as a Nexus of Metabolic and Hepatic Diseases","volume":"27","author":"Samuel","year":"2018","journal-title":"Cell Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1172\/JCI134165","article-title":"Insulin Resistance Drives Hepatic De Novo Lipogenesis in Nonalcoholic Fatty Liver Disease","volume":"130","author":"Smith","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1002\/hep.29367","article-title":"The Diagnosis and Management of Nonalcoholic Fatty Liver Disease: Practice Guidance from the American Association for the Study of Liver Diseases","volume":"67","author":"Chalasani","year":"2018","journal-title":"Hepatology"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Barber\u00eda-Latasa, M., Mart\u00ednez-Urbistondo, D., and Mart\u00ednez-Gonz\u00e1lez, M.A. (2025). The Role of the Mediterranean Diet and Alcohol Consumption in Chronic Liver Disease Prevention: A Narrative Review. Medicina, 61.","DOI":"10.3390\/medicina61101777"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Wang, L., Zhou, H., Liu, Y., Wang, X., Yan, W., Zhang, J., and Ren, H. (2023). Factors Influencing Adherence to Lifestyle Prescriptions among Patients with Nonalcoholic Fatty Liver Disease: A Qualitative Study Using the Health Action Process Approach Framework. Front. Public Health, 11.","DOI":"10.3389\/fpubh.2023.1131827"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"155676","DOI":"10.1016\/j.metabol.2023.155676","article-title":"Sarcopenia, Sarcopenic Obesity and Nonalcoholic Fatty Liver Disease","volume":"147","author":"Polyzos","year":"2023","journal-title":"Metabolism"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1007\/s12072-019-09996-7","article-title":"Sarcopenia and Fatty Liver Disease","volume":"13","author":"Kim","year":"2019","journal-title":"Hepatol. Int."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Babu, A.F., Csader, S., Lok, J., G\u00f3mez-Gallego, C., Hanhineva, K., El-Nezami, H., and Schwab, U. (2021). Positive Effects of Exercise Intervention without Weight Loss and Dietary Changes in NAFLD-Related Clinical Parameters: A Systematic Review and Meta-Analysis. Nutrients, 13.","DOI":"10.3390\/nu13093135"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.cgh.2016.07.031","article-title":"Exercise Reduces Liver Lipids and Visceral Adiposity in Patients with Nonalcoholic Steatohepatitis in a Randomized Controlled Trial","volume":"15","author":"Houghton","year":"2017","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e0711","DOI":"10.1097\/HC9.0000000000000711","article-title":"Skeletal Muscle and MASLD: Mechanistic and Clinical Insights","volume":"9","author":"Marjot","year":"2025","journal-title":"Hepatol. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1001\/jama.2020.2298","article-title":"Nonalcoholic Steatohepatitis: A Review","volume":"323","author":"Sheka","year":"2020","journal-title":"JAMA"},{"key":"ref_19","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_20","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1007\/s40265-024-02045-0","article-title":"Resmetirom: First Approval","volume":"84","author":"Keam","year":"2024","journal-title":"Drugs"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1080\/14656566.2025.2478917","article-title":"Resmetirom: The First Approved Therapy for Treating Metabolic Dysfunction Associated Steatohepatitis","volume":"26","author":"Bhushan","year":"2025","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e70132","DOI":"10.1111\/eci.70132","article-title":"Metabolic Dysfunction-Associated Steatotic Liver Disease, Insulin Resistance and Hepatocellular Carcinoma: A Deadly Triad","volume":"56","author":"Caturano","year":"2025","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_23","first-page":"e71095","article-title":"The Link Between Metabolic Dysfunction-Associated Steatotic Liver Disease and Gastroesophageal Reflux Disease","volume":"16","author":"Dutta","year":"2024","journal-title":"Cureus"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1172\/JCI77812","article-title":"The Pathogenesis of Insulin Resistance: Integrating Signaling Pathways and Substrate Flux","volume":"126","author":"Samuel","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1172\/JCI200422422","article-title":"Molecular Mediators of Hepatic Steatosis and Liver Injury","volume":"114","author":"Browning","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_26","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_27","doi-asserted-by":"crossref","first-page":"e70132","DOI":"10.1002\/edm2.70132","article-title":"Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Mechanisms, Clinical Implications and Therapeutic Advances","volume":"8","author":"Miller","year":"2025","journal-title":"Endocrinol. Diabetes Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1172\/JCI34275","article-title":"Contribution of De Novo Fatty Acid Synthesis to Hepatic Steatosis and Insulin Resistance: Lessons from Genetically Engineered Mice","volume":"118","author":"Postic","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"210","DOI":"10.3350\/cmh.2013.19.3.210","article-title":"Nonalcoholic Fatty Liver Disease: Molecular Mechanisms for Hepatic Steatosis","volume":"19","author":"Koo","year":"2013","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_30","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_31","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_32","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_33","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1161\/ATVBAHA.111.241463","article-title":"Selective hepatic insulin resistance, VLDL overproduction, and hypertriglyceridemia","volume":"32","author":"Sparks","year":"2012","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"12587","DOI":"10.1073\/pnas.0705408104","article-title":"The Role of Skeletal Muscle Insulin Resistance in the Pathogenesis of the Metabolic Syndrome","volume":"104","author":"Petersen","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1056\/NEJM199610313351804","article-title":"Increased Glucose Transport-Phosphorylation and Muscle Glycogen Synthesis after Exercise Training in Insulin-Resistant Subjects","volume":"335","author":"Perseghin","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"517","DOI":"10.2337\/dbi18-0043","article-title":"Exercise Combats Hepatic Steatosis: Potential Mechanisms and Clinical Implications","volume":"69","author":"Thyfault","year":"2020","journal-title":"Diabetes"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Radosavljevic, T., Brankovic, M., Samardzic, J., Djureti\u0107, J., Vukicevic, D., Vucevic, D., and Jakovljevic, V. (2024). Altered Mitochondrial Function in MASLD: Key Features and Promising Therapeutic Approaches. Antioxidants, 13.","DOI":"10.3390\/antiox13080906"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1152\/physrev.90100.2007","article-title":"Muscle as an Endocrine Organ: Focus on Muscle-Derived Interleukin-6","volume":"88","author":"Pedersen","year":"2008","journal-title":"Physiol. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Nara, H., and Watanabe, R. (2021). Anti-Inflammatory Effect of Muscle-Derived Interleukin-6 and Its Involvement in Lipid Metabolism. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22189889"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1146\/annurev-pathol-011110-130246","article-title":"Pathogenesis of Liver Fibrosis","volume":"6","author":"Friedman","year":"2011","journal-title":"Annu. Rev. Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.mam.2018.09.002","article-title":"Liver Fibrosis: Pathophysiology, Pathogenetic Targets and Clinical Issues","volume":"65","author":"Parola","year":"2019","journal-title":"Mol. Asp. Med."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Sandireddy, R., Sakthivel, S., Gupta, P., Behari, J., Tripathi, M., and Singh, B.K. (2024). Systemic Impacts of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic Dysfunction-Associated Steatohepatitis (MASH) on Heart, Muscle, and Kidney Related Diseases. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1433857"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"118868","DOI":"10.1016\/j.lfs.2020.118868","article-title":"Aerobic Training Improves NAFLD Markers and Insulin Resistance through AMPK\u2013PPAR-\u03b1 Signaling in Obese Mice","volume":"266","author":"Diniz","year":"2021","journal-title":"Life Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"8391","DOI":"10.1038\/s41467-023-44242-7","article-title":"Cdo1\u2013Camkk2\u2013AMPK Axis Confers the Protective Effects of Exercise against NAFLD in Mice","volume":"14","author":"Chen","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Wang, Y., Yu, W., Li, S., Guo, D., He, J., and Wang, Y. (2022). Acetyl-CoA Carboxylases and Diseases. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.836058"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1186\/s12944-018-0852-z","article-title":"Exercise without Dietary Changes Alleviates Nonalcoholic Fatty Liver Disease without Weight Loss Benefits","volume":"17","author":"Ok","year":"2018","journal-title":"Lipids Health Dis."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Bae, J.Y. (2020). Resistance Exercise Regulates Hepatic Lipolytic Factors as Effective as Aerobic Exercise in Obese Mice. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17228307"},{"key":"ref_48","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_49","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1002\/hep.23129","article-title":"Aerobic Exercise Training Reduces Hepatic and Visceral Lipids in Obese Individuals without Weight Loss","volume":"50","author":"Johnson","year":"2009","journal-title":"Hepatology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1002\/hep.26393","article-title":"Both Resistance Training and Aerobic Training Reduce Hepatic Fat Content in Type 2 Diabetic Subjects with Nonalcoholic Fatty Liver Disease (the RAED2 Randomized Trial)","volume":"58","author":"Bacchi","year":"2013","journal-title":"Hepatology"},{"key":"ref_51","first-page":"1452696","article-title":"PGC-1\u03b1, Inflammation, and Oxidative Stress: An Integrative View in Metabolism","volume":"2020","author":"Ortega","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"E145","DOI":"10.1152\/ajpendo.00755.2009","article-title":"PGC-1\u03b1 Regulation by Exercise Training and Its Influences on Muscle Function and Insulin Sensitivity","volume":"299","author":"Lira","year":"2010","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Fang, C., Pan, J., Qu, N., Lei, Y., Han, J., Zhang, J., and Han, D. (2022). The AMPK Pathway in Fatty Liver Disease. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.970292"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Foretz, M., Even, P.C., and Viollet, B. (2018). AMPK Activation Reduces Hepatic Lipid Content by Increasing Fat Oxidation In Vivo. Int. J. Mol. Sci., 19.","DOI":"10.20944\/preprints201808.0026.v1"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1016\/j.cgh.2016.04.036","article-title":"Exercise-Based Interventions for Nonalcoholic Fatty Liver Disease: A Meta-Analysis and Meta-Regression","volume":"14","author":"Orci","year":"2016","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_56","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_57","doi-asserted-by":"crossref","unstructured":"Xiong, Y., Peng, Q., Cao, C., Xu, Z., and Zhang, B. (2021). Effect of Different Exercise Methods on Non-Alcoholic Fatty Liver Disease: A Meta-Analysis and Meta-Regression. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18063242"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1152\/japplphysiol.00843.2011","article-title":"Aerobic Exercise Training Conserves Insulin Sensitivity for One Year Following Weight Loss in Overweight Women","volume":"112","author":"Fisher","year":"2012","journal-title":"J. Appl. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e2452185","DOI":"10.1001\/jamanetworkopen.2024.52185","article-title":"Aerobic Exercise and Weight Loss in Adults: A Systematic Review and Dose-Response Meta-Analysis","volume":"7","author":"Jayedi","year":"2024","journal-title":"JAMA Netw. Open"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"294","DOI":"10.2337\/diabetes.53.2.294","article-title":"Strength Training Increases Insulin-Mediated Glucose Uptake, GLUT4 Content, and Insulin Signaling in Skeletal Muscle in Patients with Type 2 Diabetes","volume":"53","author":"Holten","year":"2004","journal-title":"Diabetes"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1139\/H07-129","article-title":"Resistance Exercise: Good for More Than Just Grandma and Grandpa\u2019s Muscles","volume":"32","author":"Phillips","year":"2007","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"S157","DOI":"10.2337\/dc09-S302","article-title":"Skeletal Muscle Insulin Resistance Is the Primary Defect in Type 2 Diabetes","volume":"32","author":"DeFronzo","year":"2009","journal-title":"Diabetes Care"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/j.cell.2012.02.017","article-title":"Mechanisms for Insulin Resistance: Common Threads and Missing Links","volume":"148","author":"Samuel","year":"2012","journal-title":"Cell"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Nishikawa, H., Kim, S.K., and Asai, A. (2025). The Role of Myokines in Liver Diseases. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26031043"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Dumond Bourie, A., Potier, J.B., Pinget, M., and Bouzakri, K. (2023). Myokines: Crosstalk and Consequences on Liver Physiopathology. Nutrients, 15.","DOI":"10.3390\/nu15071729"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nature10777","article-title":"A PGC-1\u03b1-Dependent Myokine That Drives Brown-Fat-Like Development of White Fat and Thermogenesis","volume":"481","author":"Wu","year":"2012","journal-title":"Nature"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1016\/j.cellsig.2015.04.010","article-title":"New Role of Irisin in Hepatocytes: The Protective Effect of Hepatic Steatosis In Vitro","volume":"27","author":"Park","year":"2015","journal-title":"Cell. Signal."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Henkel, J., Buchheim-Dieckow, K., Castro, J.P., Laeger, T., Wardelmann, K., Kleinridders, A., J\u00f6hrens, K., and P\u00fcschel, G.P. (2019). Reduced Oxidative Stress and Enhanced FGF21 Formation in Livers of Endurance-Exercised Rats with Diet-Induced NASH. Nutrients, 11.","DOI":"10.3390\/nu11112709"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Cuevas-Ramos, D., Almeda-Vald\u00e9s, P., Meza-Arana, C.E., Brito-C\u00f3rdova, G., G\u00f3mez-P\u00e9rez, F.J., Mehta, R., Oseguera-Moguel, J., and Aguilar-Salinas, C.A. (2012). Exercise Increases Serum Fibroblast Growth Factor 21 (FGF21) Levels. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038022"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1055\/a-1778-4159","article-title":"FGF21: A novel regulator of glucose and lipid metabolism and whole-body energy balance","volume":"54","year":"2022","journal-title":"Horm. Metab. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"103910","DOI":"10.1016\/j.drudis.2024.103910","article-title":"NAFLD and NASH: Etiology, targets and emerging therapies","volume":"29","author":"Wei","year":"2024","journal-title":"Drug Discov. Today"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e20399","DOI":"10.1097\/MD.0000000000020399","article-title":"Simple Resistance Exercise Decreases Cytokeratin 18 and Fibroblast Growth Factor 21 Levels in Patients with Nonalcoholic Fatty Liver Disease: A Retrospective Clinical Study","volume":"99","author":"Takahashi","year":"2020","journal-title":"Medicine"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Stine, J.G., Welles, J.E., Keating, S., Hussaini, Z., Soriano, C., Heinle, J.W., Geyer, N., Chinchilli, V.M., Loomba, R., and Kimball, S.R. (2023). Serum Fibroblast Growth Factor 21 Is Markedly Decreased following Exercise Training in Patients with Biopsy-Proven Nonalcoholic Steatohepatitis. Nutrients, 15.","DOI":"10.3390\/nu15061481"},{"key":"ref_74","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_75","doi-asserted-by":"crossref","first-page":"4382","DOI":"10.3748\/wjg.v20.i15.4382","article-title":"Effect of Resistance Training on Non-Alcoholic Fatty Liver Disease: A Randomized Clinical Trial","volume":"20","author":"Buch","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_76","first-page":"E118","article-title":"Resistance Training Reduces the Acute Exercise-Induced Increase in Muscle Protein Turnover","volume":"276","author":"Phillips","year":"1999","journal-title":"Am. J. Physiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/obr.12257","article-title":"Appetite control and energy balance: Impact of exercise","volume":"16","author":"Blundell","year":"2015","journal-title":"Obes. Rev."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.jhep.2017.05.016","article-title":"Treatment of NAFLD with Diet, Physical Activity and Exercise","volume":"67","author":"Trenell","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"G619","DOI":"10.1152\/ajpgi.00428.2007","article-title":"Daily Exercise Increases Hepatic Fatty Acid Oxidation and Prevents Steatosis in Otsuka Long-Evans Tokushima Fatty Rats","volume":"294","author":"Rector","year":"2008","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e00316","DOI":"10.14309\/ctg.0000000000000316","article-title":"Moderate-Intensity Aerobic vs Resistance Exercise and Dietary Modification in Patients with Nonalcoholic Fatty Liver Disease: A Randomized Clinical Trial","volume":"12","author":"Charatcharoenwitthaya","year":"2021","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"600","DOI":"10.5009\/gnl220345","article-title":"Independent and Synergistic Associations of Aerobic Physical Activity and Resistance Exercise with Nonalcoholic Fatty Liver Disease","volume":"17","author":"Yang","year":"2023","journal-title":"Gut Liver"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Hejazi, K., and Hackett, D. (2023). Effect of Exercise on Liver Function and Insulin Resistance Markers in Patients with Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J. Clin. Med., 12.","DOI":"10.3390\/jcm12083011"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e250275","DOI":"10.1530\/JOE-25-0275","article-title":"Effects of Combined Aerobic and Resistance Exercise on Sarcopenia in Elderly Patients with Type 2 Diabetes Mellitus","volume":"267","author":"Ma","year":"2025","journal-title":"J. Endocrinol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"278","DOI":"10.4235\/agmr.25.0052","article-title":"Position Statement: Evidence-Based Exercise Guidelines for Sarcopenia in Older Adults: Insights from the Korean Working Group on Sarcopenia","volume":"29","author":"Bae","year":"2025","journal-title":"Ann. Geriatr. Med. Res."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Ali, H., Shahzil, M., Moond, V., Shahzad, M., Thandavaram, A., Sehar, A., Waseem, H., Siddiqui, T., Dahiya, D.S., and Patel, P. (2024). Non-Pharmacological Approach to Diet and Exercise in Metabolic-Associated Fatty Liver Disease: Bridging the Gap between Research and Clinical Practice. J. Pers. Med., 14.","DOI":"10.3390\/jpm14010061"},{"key":"ref_86","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_87","doi-asserted-by":"crossref","first-page":"5271","DOI":"10.1113\/JP272235","article-title":"Aerobic Exercise Training in the Treatment of Non-Alcoholic Fatty Liver Disease Related Fibrosis","volume":"594","author":"Linden","year":"2016","journal-title":"J. Physiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1016\/j.bbi.2012.04.006","article-title":"Exercise Training Attenuates Hepatic Inflammation, Fibrosis and Macrophage Infiltration during Diet-Induced Obesity in Mice","volume":"26","author":"Kawanishi","year":"2012","journal-title":"Brain Behav. Immun."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1002\/oby.21170","article-title":"Exercise Improves Adipose Function and Inflammation and Ameliorates Fatty Liver Disease in Obese Diabetic Mice","volume":"23","author":"Haczeyni","year":"2015","journal-title":"Obesity"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1042\/CS20150308","article-title":"Modified High-Intensity Interval Training Reduces Liver Fat and Improves Cardiac Function in Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Trial","volume":"129","author":"Hallsworth","year":"2015","journal-title":"Clin. Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"E50","DOI":"10.1152\/ajpendo.00055.2013","article-title":"Exercise Training Improves Cutaneous Microvascular Function in Nonalcoholic Fatty Liver Disease","volume":"305","author":"Pugh","year":"2013","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1249\/MSS.0b013e31829afc33","article-title":"Exercise Reduces Inflammation and Oxidative Stress in Obesity-Related Liver Diseases","volume":"45","author":"Oh","year":"2013","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1038\/s12276-020-0459-0","article-title":"Exercise Training Modulates the Gut Microbiota Profile and Impairs Inflammatory Signaling Pathways in Obese Children","volume":"52","author":"Quiroga","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"414","DOI":"10.3350\/cmh.2023.0055","article-title":"The Independent Effect of Exercise on Biopsy Proven Non-Alcoholic Fatty Liver Disease: A Systematic Review","volume":"29","author":"Jin","year":"2023","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.jhep.2016.08.023","article-title":"Aerobic vs. Resistance Exercise in Non-Alcoholic Fatty Liver Disease: A Systematic Review","volume":"66","author":"Hashida","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1097\/MOL.0b013e328328d0a4","article-title":"PGC-1\u03b1, SIRT1 and AMPK: An Energy-Sensing Network That Controls Energy Expenditure","volume":"20","author":"Auwerx","year":"2009","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.diabres.2008.11.024","article-title":"Resistance Training Improves Metabolic Health in Type 2 Diabetes: A Systematic Review","volume":"83","author":"Gordon","year":"2009","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"487","DOI":"10.5009\/gnl230232","article-title":"Synergistic Preventive Effect of Aerobic and Resistance Exercises on Nonalcoholic Fatty Liver Disease","volume":"17","author":"Cho","year":"2023","journal-title":"Gut Liver"},{"key":"ref_99","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_100","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1007\/s12072-020-10094-2","article-title":"The Asian Pacific Association for the Study of the Liver Clinical Practice Guidelines for the Diagnosis and Management of Metabolic Associated Fatty Liver Disease","volume":"14","author":"Eslam","year":"2020","journal-title":"Hepatol. Int."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e15227","DOI":"10.5812\/hepatmon.15227","article-title":"How Much Weight Loss Is Effective on Nonalcoholic Fatty Liver Disease?","volume":"13","author":"Ghaemi","year":"2013","journal-title":"Hepat. Mon."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"154455","DOI":"10.1016\/j.metabol.2020.154455","article-title":"The Effect of the Magnitude of Weight Loss on Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis","volume":"115","author":"Koutoukidis","year":"2021","journal-title":"Metabolism"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.mcna.2017.08.012","article-title":"Maintenance of Lost Weight and Long-Term Management of Obesity","volume":"102","author":"Hall","year":"2018","journal-title":"Med. Clin. N. Am."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"111561","DOI":"10.1016\/j.exger.2021.111561","article-title":"Aging, Obesity, Sarcopenia and the Effect of Diet and Exercise Intervention","volume":"155","author":"Colleluori","year":"2021","journal-title":"Exp. Gerontol."},{"key":"ref_105","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_106","doi-asserted-by":"crossref","first-page":"100253","DOI":"10.1016\/j.jhepr.2021.100253","article-title":"Weight-Loss-Independent Benefits of Exercise on Liver Steatosis and Stiffness in Japanese Men with NAFLD","volume":"3","author":"Oh","year":"2021","journal-title":"JHEP Rep."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Barr\u00f3n-Cabrera, E., Soria-Rodr\u00edguez, R., Amador-Lara, F., and Mart\u00ednez-L\u00f3pez, E. (2023). Physical Activity Protocols in Non-Alcoholic Fatty Liver Disease Management: A Systematic Review of Randomized Clinical Trials and Animal Models. Healthcare, 11.","DOI":"10.3390\/healthcare11141992"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.jhep.2012.02.023","article-title":"Exercise and Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis","volume":"57","author":"Keating","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/sms.12581","article-title":"Exercise as Medicine\u2014Evidence for Prescribing Exercise as Therapy in 26 Different Chronic Diseases","volume":"25","author":"Pedersen","year":"2015","journal-title":"Scand. J. Med. Sci. Sports"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1056\/NEJMoa2032183","article-title":"Once-Weekly Semaglutide in Adults with Overweight or Obesity","volume":"384","author":"Wilding","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1056\/NEJMoa2206038","article-title":"Tirzepatide Once Weekly for the Treatment of Obesity","volume":"387","author":"Jastreboff","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/j.amjmed.2025.01.021","article-title":"Mechanisms of GLP-1 receptor agonist-induced weight loss: A review of central and peripheral pathways in appetite and energy regulation","volume":"138","author":"Moiz","year":"2025","journal-title":"Am. J. Med."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Voudouris, D., Horianopoulou, M., Apostolopoulou, Z., Chryssanthopoulos, C., Bardopoulou, M., Maridaki, M., Vassilakopoulos, T., Koutsilieris, M., and Philippou, A. (2023). The Effects of a Short-Term Combined Exercise Program on Liver Steatosis Indices and the Lipidemic and Glycemic Profile in NAFLD Individuals: A Pilot Study. Metabolites, 13.","DOI":"10.3390\/metabo13101074"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Sardeli, A.V., Komatsu, T.R., Mori, M.A., G\u00e1spari, A.F., and Chacon-Mikahil, M.P.T. (2018). Resistance Training Prevents Muscle Loss Induced by Caloric Restriction in Obese Elderly Individuals: A Systematic Review and Meta-Analysis. Nutrients, 10.","DOI":"10.3390\/nu10040423"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Beaudart, C., Zaaria, M., Pasleau, F., Reginster, J.Y., and Bruy\u00e8re, O. (2017). Health Outcomes of Sarcopenia: A Systematic Review and Meta-Analysis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0169548"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1249\/MSS.0b013e318213fefb","article-title":"American College of Sports Medicine Position Stand: Quantity and Quality of Exercise for Developing and Maintaining Cardiorespiratory, Musculoskeletal, and Neuromotor Fitness in Apparently Healthy Adults: Guidance for Prescribing Exercise","volume":"43","author":"Garber","year":"2011","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1001\/jama.2018.14854","article-title":"The Physical Activity Guidelines for Americans","volume":"320","author":"Piercy","year":"2018","journal-title":"JAMA"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1007\/s40279-023-01918-w","article-title":"Exercise in the Management of Metabolic-Associated Fatty Liver Disease (MAFLD) in Adults: A Position Statement from Exercise and Sport Science Australia","volume":"53","author":"Keating","year":"2023","journal-title":"Sports Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"10128","DOI":"10.3748\/wjg.v20.i29.10128","article-title":"Physical Activity Support or Weight Loss Counseling for Nonalcoholic Fatty Liver Disease?","volume":"20","author":"Montesi","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1123\/jpah.9.2.198","article-title":"Injuries in Sedentary Individuals Enrolled in a 12-Month Randomized Controlled Exercise Trial","volume":"9","author":"Campbell","year":"2012","journal-title":"J. Phys. Act. Health"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1249\/MSS.0000000000000664","article-title":"Updating ACSM\u2019s Recommendations for Exercise Preparticipation Health Screening","volume":"47","author":"Riebe","year":"2015","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"94","DOI":"10.14740\/jocmr5113","article-title":"Barriers to Exercise in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease: A Patient Survey","volume":"16","author":"Deshpande","year":"2024","journal-title":"J. Clin. Med. Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.maturitas.2019.03.016","article-title":"Nonalcoholic Fatty Liver Disease in the Over-60s: Impact of Sarcopenia and Obesity","volume":"124","author":"Wijarnpreecha","year":"2019","journal-title":"Maturitas"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"130","DOI":"10.5009\/gnl220041","article-title":"Association between Sarcopenic Obesity Status and Nonalcoholic Fatty Liver Disease and Fibrosis","volume":"17","author":"Song","year":"2023","journal-title":"Gut Liver"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/dom.15728","article-title":"Changes in lean body mass with glucagon-like peptide-1-based therapies and mitigation strategies","volume":"26","author":"Neeland","year":"2024","journal-title":"Diabetes Obes. Metab."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"e13915","DOI":"10.1111\/apha.13915","article-title":"The role of the circadian clock in the development, progression, and treatment of non-alcoholic fatty liver disease","volume":"237","author":"Demir","year":"2023","journal-title":"Acta Physiol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"101235","DOI":"10.1016\/j.plipres.2023.101235","article-title":"Lipid metabolism around the body clocks","volume":"91","author":"Petrenko","year":"2023","journal-title":"Prog. Lipid Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1007\/s00109-019-01780-2","article-title":"Circadian rhythms: A possible new player in non-alcoholic fatty liver disease pathophysiology","volume":"97","author":"Gnocchi","year":"2019","journal-title":"J. Mol. Med."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/4\/784\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T04:13:05Z","timestamp":1776744785000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/4\/784"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,18]]},"references-count":128,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["medicina62040784"],"URL":"https:\/\/doi.org\/10.3390\/medicina62040784","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,18]]}}}