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Among other factors, an aberrant lipid metabolism represents a crucial step in the pathogenesis of NAFLD and the development of HCC in this population. In this review, we summarize the evidence supporting the application of translational lipidomics in NAFLD patients and NAFLD associated HCC in clinical practice.<\/jats:p>","DOI":"10.3390\/nu15081992","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T01:33:43Z","timestamp":1682040823000},"page":"1992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Applying Lipidomics to Non-Alcoholic Fatty Liver Disease: A Clinical Perspective"],"prefix":"10.3390","volume":"15","author":[{"given":"Jian","family":"Huang","sequence":"first","affiliation":[{"name":"Liver Unit, Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London W21NY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giordano","family":"Sigon","sequence":"additional","affiliation":[{"name":"Liver Unit, Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London W21NY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6300-3100","authenticated-orcid":false,"given":"Benjamin H.","family":"Mullish","sequence":"additional","affiliation":[{"name":"Liver Unit, Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London W21NY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Wang","sequence":"additional","affiliation":[{"name":"Liver Unit, Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London W21NY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2441-549X","authenticated-orcid":false,"given":"Rohini","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, London W21NY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pinelopi","family":"Manousou","sequence":"additional","affiliation":[{"name":"Liver Unit, Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London W21NY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4746-7065","authenticated-orcid":false,"given":"Roberta","family":"Forlano","sequence":"additional","affiliation":[{"name":"Liver Unit, Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London W21NY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1053\/j.gastro.2007.04.061","article-title":"Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis","volume":"132","author":"Rudolph","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21708","article-title":"Cancer statistics, 2022. CA","volume":"72","author":"Siegel","year":"2022","journal-title":"Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1126\/science.1204265","article-title":"Human fatty liver disease: Old questions and new insights","volume":"332","author":"Cohen","year":"2011","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"13734","DOI":"10.1038\/s41598-018-31953-x","article-title":"Histone H3K9 demethylase JMJD2B induces hepatic steatosis through upregulation of PPAR\u03b32","volume":"8","author":"Kim","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4574","DOI":"10.2174\/1381612825666190117102111","article-title":"Diagnosis of non-alcoholic fatty liver disease (NAFLD): Current concepts","volume":"24","author":"Papatheodoridi","year":"2018","journal-title":"Curr. Pharm. Des."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Roehlen, N., Crouchet, E., and Baumert, T.F. (2020). Liver fibrosis: Mechanistic concepts and therapeutic perspectives. Cells, 9.","DOI":"10.3390\/cells9040875"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Brankovi\u0107, M., Jovanovi\u0107, I., Duki\u0107, M., Radonji\u0107, T., Opri\u0107, S., Kla\u0161nja, S., and Zdravkovi\u0107, M. (2022). Lipotoxicity as the Leading Cause of Non-Alcoholic Steatohepatitis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23095146"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Kim, H., Lee, D.S., An, T.H., Park, H.-J., Kim, W.K., Bae, K.-H., and Oh, K.-J. (2021). Metabolic Spectrum of Liver Failure in Type 2 Diabetes and Obesity: From NAFLD to NASH to HCC. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094495"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1002\/hep.28123","article-title":"Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009","volume":"62","author":"Younossi","year":"2015","journal-title":"Hepatology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/liv.13502","article-title":"Hepatocellular carcinoma in South America: Evaluation of risk factors, demographics and therapy","volume":"38","author":"Debes","year":"2018","journal-title":"Liver Int."},{"key":"ref_11","first-page":"681A","article-title":"Changing epidemiology of hepatocellular carcinoma in south america: A report from the escalon network","volume":"Volume 74","author":"Farah","year":"2021","journal-title":"Hepatology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1111\/liv.14857","article-title":"SPARC inhibition accelerates NAFLD-associated hepatocellular carcinoma development by dysregulating hepatic lipid metabolism","volume":"41","author":"Onorato","year":"2021","journal-title":"Liver Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1016\/j.cmet.2022.09.023","article-title":"The role of lipids in cancer progression and metastasis","volume":"34","author":"Bigas","year":"2022","journal-title":"Cell Metab."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Ma, X., and Fern\u00e1ndez, F.M. (2022). Advances in mass spectrometry imaging for spatial cancer metabolomics. Mass Spectrom. Rev., e21804.","DOI":"10.1002\/mas.21804"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1038\/s12276-022-00838-5","article-title":"Measurement of lipid flux to advance translational research: Evolution of classic methods to the future of precision health","volume":"54","author":"Salvador","year":"2022","journal-title":"Exp. Mol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"C630","DOI":"10.1152\/ajpcell.00123.2022","article-title":"Role of hepatic lipid species in the progression of nonalcoholic fatty liver disease","volume":"323","author":"Deng","year":"2022","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Li, Z., Guan, M., Lin, Y., Cui, X., Zhang, Y., Zhao, Z., and Zhu, J. (2017). Aberrant lipid metabolism in hepatocellular carcinoma revealed by liver lipidomics. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122550"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.chroma.2015.01.013","article-title":"Ultra-high-performance liquid chromatography electrospray ionization tandem mass spectrometry for accurate analysis of glycerophospholipids and sphingolipids in drug resistance tumor cells","volume":"1381","author":"Li","year":"2015","journal-title":"J. Chromatogr. A"},{"key":"ref_19","unstructured":"Oskouian, B., and Saba, J.D. (2010). Sphingolipids as Signaling and Regulatory Molecules, Springer."},{"key":"ref_20","first-page":"637","article-title":"Lipid classification, structures and tools","volume":"1811","author":"Fahy","year":"2011","journal-title":"Biochim. Biophys. Acta BBA-Mol. Cell Biol. Lipids"},{"key":"ref_21","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_22","unstructured":"Ahmed, S., Shah, P., and Ahmed, O. (2022, May 10). Biochemistry, Lipids, StatPearls, Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK525952\/."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"D527","DOI":"10.1093\/nar\/gkl838","article-title":"LMSD: LIPID MAPS structure database","volume":"35","author":"Sud","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6409","DOI":"10.1021\/ja029029o","article-title":"Polyunsaturated Docosahexaenoic vs Docosapentaenoic AcidDifferences in Lipid Matrix Properties from the Loss of One Double Bond","volume":"125","author":"Eldho","year":"2003","journal-title":"J. Am. Chem. Soc."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.chemphyslip.2008.02.007","article-title":"Docosahexaenoic Acid (DHA) and Hepatic Gene Transcription","volume":"153","author":"Jump","year":"2008","journal-title":"Chem. Phys. Lipids"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1038\/nrendo.2017.91","article-title":"SREBP-regulated lipid metabolism: Convergent physiology\u2014Divergent pathophysiology","volume":"13","author":"Shimano","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1172\/JCI0215593","article-title":"SREBPs: Activators of the complete program of cholesterol and fatty acid synthesis in the liver","volume":"109","author":"Horton","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"bqz046","DOI":"10.1210\/endocr\/bqz046","article-title":"CPT1A-mediated fat oxidation, mechanisms, and therapeutic potential","volume":"161","author":"Schlaepfer","year":"2020","journal-title":"Endocrinology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"ra82","DOI":"10.1126\/scisignal.2000446","article-title":"EGFR signaling through an Akt-SREBP-1\u2013dependent, rapamycin-resistant pathway sensitizes glioblastomas to antilipogenic therapy","volume":"2","author":"Guo","year":"2009","journal-title":"Sci. Signal."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1158\/2159-8290.CD-11-0102","article-title":"An LXR agonist promotes glioblastoma cell death through inhibition of an EGFR\/AKT\/SREBP-1\/LDLR\u2013dependent pathway","volume":"1","author":"Guo","year":"2011","journal-title":"Cancer Discov."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1900385","DOI":"10.1002\/mnfr.201900385","article-title":"Industrial Trans Fatty Acids Stimulate SREBP2-Mediated Cholesterogenesis and Promote Non-Alcoholic Fatty Liver Disease","volume":"63","author":"Oteng","year":"2019","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1136\/gutjnl-2019-319664","article-title":"Dietary cholesterol drives fatty liver-associated liver cancer by modulating gut microbiota and metabolites","volume":"70","author":"Zhang","year":"2021","journal-title":"Gut"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/s41423-022-00872-3","article-title":"Aberrant cholesterol metabolic signaling impairs antitumor immunosurveillance through natural killer T cell dysfunction in obese liver","volume":"19","author":"Tang","year":"2022","journal-title":"Cell. Mol. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1006\/geno.2002.6845","article-title":"A novel brain-expressed protein related to carnitine palmitoyltransferase I","volume":"80","author":"Price","year":"2002","journal-title":"Genomics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1006\/geno.1997.5184","article-title":"Genomic DNA sequence, promoter expression, and chromosomal mapping of rat muscle carnitine palmitoyltransferase I","volume":"48","author":"Wang","year":"1998","journal-title":"Genomics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.1007\/s00018-009-0035-1","article-title":"Structural insight into function and regulation of carnitine palmitoyltransferase","volume":"66","author":"Rufer","year":"2009","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1042\/bst0290310","article-title":"Regulation of liver carnitine palmitoyltransferase I gene expression by hormones and fatty acids","volume":"29","author":"Louet","year":"2001","journal-title":"Biochem. Soc. Trans."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.mce.2010.05.019","article-title":"Peroxisome proliferator activated receptor \u03b1 (PPAR\u03b1) and PPAR gamma coactivator (PGC-1\u03b1) induce carnitine palmitoyltransferase IA (CPT-1A) via independent gene elements","volume":"325","author":"Song","year":"2010","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.jmb.2005.09.097","article-title":"An intronic peroxisome proliferator-activated receptor-binding sequence mediates fatty acid induction of the human carnitine palmitoyltransferase 1A","volume":"354","author":"Napal","year":"2005","journal-title":"J. Mol. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3009","DOI":"10.3748\/wjg.v25.i24.3009","article-title":"Biomarkers and subtypes of deranged lipid metabolism in non-alcoholic fatty liver disease","volume":"25","author":"Mato","year":"2019","journal-title":"World J. Gastroenterol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3313","DOI":"10.1007\/s00018-018-2860-6","article-title":"Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease","volume":"75","author":"Ipsen","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.plipres.2012.11.002","article-title":"Cholesterol metabolism and the pathogenesis of non-alcoholic steatohepatitis","volume":"52","author":"Musso","year":"2013","journal-title":"Prog. Lipid Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.jhep.2017.09.012","article-title":"Association between non-alcoholic fatty liver disease and cancer incidence rate","volume":"68","author":"Kim","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Sunami, Y. (2020). NASH, fibrosis and hepatocellular carcinoma: Lipid synthesis and glutamine\/acetate signaling. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186799"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1038\/s41419-020-03003-w","article-title":"Understanding lipotoxicity in NAFLD pathogenesis: Is CD36 a key driver?","volume":"11","author":"Rada","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"14859","DOI":"10.1038\/ncomms14859","article-title":"Pharmacological inhibition of adipose triglyceride lipase corrects high-fat diet-induced insulin resistance and hepatosteatosis in mice","volume":"8","author":"Schweiger","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_47","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_48","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1136\/gutjnl-2012-302962","article-title":"Epigenetic modification of liver mitochondrial DNA is associated with histological severity of nonalcoholic fatty liver disease","volume":"62","author":"Pirola","year":"2012","journal-title":"Gut"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.metabol.2013.10.009","article-title":"Palmitate-induced Activation of Mitochondrial Metabolism Promotes Oxidative Stress and Apoptosis in H4IIEC3 Rat Hepatocytes","volume":"63","author":"Egnatchik","year":"2014","journal-title":"Metabolism"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.freeradbiomed.2019.05.029","article-title":"Lipidomic biomarkers and mechanisms of lipotoxicity in non-alcoholic fatty liver disease","volume":"144","author":"Pierantonelli","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"E484","DOI":"10.1152\/ajpendo.00492.2015","article-title":"Lipotoxicity in steatohepatitis occurs despite an increase in tricarboxylic acid cycle activity","volume":"310","author":"Patterson","year":"2016","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"101432","DOI":"10.1016\/j.diabet.2023.101432","article-title":"Concise review of lipidomics in nonalcoholic fatty liver disease","volume":"49","author":"Rouland","year":"2023","journal-title":"Diabetes Metab."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1053\/j.gastro.2015.12.037","article-title":"Lipid-induced signaling causes release of inflammatory extracellular vesicles from hepatocytes","volume":"150","author":"Hirsova","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1096\/fj.201601393R","article-title":"Defective lysosomal clearance of autophagosomes and its clinical implications in nonalcoholic steatohepatitis","volume":"32","author":"Wang","year":"2018","journal-title":"FASEB J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/s41418-019-0356-z","article-title":"SIRT3 promotes lipophagy and chaperon-mediated autophagy to protect hepatocytes against lipotoxicity","volume":"27","author":"Zhang","year":"2019","journal-title":"Cell Death Differ."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.jhep.2017.11.014","article-title":"Lipotoxicity and the gut-liver axis in NASH pathogenesis","volume":"68","author":"Marra","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1002\/hep.28289","article-title":"Inhibition of hedgehog signaling ameliorates hepatic inflammation in mice with nonalcoholic fatty liver disease","volume":"63","author":"Kwon","year":"2015","journal-title":"Hepatol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3015","DOI":"10.1172\/JCI28898","article-title":"TLR4 links innate immunity and fatty acid\u2013induced insulin resistance","volume":"116","author":"Shi","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1053\/j.gastro.2016.03.008","article-title":"Biopsy and noninvasive methods to assess progression of nonalcoholic fatty liver disease","volume":"150","author":"Bedossa","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1194\/jlr.M085613","article-title":"Mitochondrial dysfunction-related lipid changes occur in nonalcoholic fatty liver disease progression","volume":"59","author":"Peng","year":"2018","journal-title":"J. Lipid Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5032","DOI":"10.18632\/oncotarget.23494","article-title":"Comparison of hepatic and serum lipid signatures in hepatocellular carcinoma patients leads to the discovery of diagnostic and prognostic biomarkers","volume":"9","author":"Lu","year":"2018","journal-title":"Oncotarget"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1016\/j.bbalip.2016.08.014","article-title":"Ceramide and polyunsaturated phospholipids are strongly reduced in human hepatocellular carcinoma","volume":"1861","author":"Krautbauer","year":"2016","journal-title":"Mol. Cell Biol. Lipids"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jhep.2007.01.030","article-title":"Prevention of hepatocarcinogenesis with phosphatidylcholine and menaquinone-4: In vitro and in vivo experiments","volume":"47","author":"Sakakima","year":"2007","journal-title":"J. Hepatol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1172\/JCI6223","article-title":"Peroxisome proliferator\u2013activated receptor \u03b1 mediates the adaptive response to fasting","volume":"103","author":"Kersten","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"7473","DOI":"10.1073\/pnas.96.13.7473","article-title":"A critical role for the peroxisome proliferator-activated receptor \u03b1 (PPAR\u03b1) in the cellular fasting response: The PPAR\u03b1-null mouse as a model of fatty acid oxidation disorders","volume":"96","author":"Leone","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.2174\/13816128113199990486","article-title":"Targeting SREBP-1-driven lipid metabolism to treat cancer","volume":"20","author":"Guo","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1002\/hep.23810","article-title":"The biliary HCO3\u2212 umbrella: A unifying hypothesis on pathogenetic and therapeutic aspects of fibrosing cholangiopathies","volume":"52","author":"Beuers","year":"2010","journal-title":"Hepatology"},{"key":"ref_68","first-page":"e1561","article-title":"Studies on the mechanisms of bile acid initiated hepatic inflammation in cholestatic liver injury","volume":"4","author":"Cai","year":"2017","journal-title":"Inflamm. Cell Signal."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1177\/0004563218817798","article-title":"Bile acids and the metabolic syndrome","volume":"56","author":"McGlone","year":"2019","journal-title":"Ann. Clin. Biochem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1194\/jlr.P056002","article-title":"Biomarkers of NAFLD progression: A lipidomics approach to an epidemic1 [S]","volume":"56","author":"Gorden","year":"2015","journal-title":"J. Lipid Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"154005","DOI":"10.1016\/j.metabol.2019.154005","article-title":"Non-invasive diagnosis of non-alcoholic steatohepatitis and fibrosis with the use of omics and supervised learning: A proof of concept study","volume":"101","author":"Perakakis","year":"2019","journal-title":"Metabolism"},{"key":"ref_72","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_73","doi-asserted-by":"crossref","unstructured":"Gorden, D.L., Ivanova, P.T., Myers, D.S., McIntyre, J.O., VanSaun, M.N., Wright, J.K., Matrisian, L.M., and Brown, H.A. (2011). Increased diacylglycerols characterize hepatic lipid changes in progression of human nonalcoholic fatty liver disease; comparison to a murine model. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0022775"},{"key":"ref_74","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_75","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1194\/jlr.P055640","article-title":"Polyunsaturated fatty acid metabolites as novel lipidomic biomarkers for noninvasive diagnosis of nonalcoholic steatohepatitis1","volume":"56","author":"Loomba","year":"2015","journal-title":"J. Lipid Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"46658","DOI":"10.1038\/srep46658","article-title":"Metabolism dysregulation induces a specific lipid signature of nonalcoholic steatohepatitis in patients","volume":"7","author":"Chiappini","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5130","DOI":"10.1021\/acs.analchem.7b05215","article-title":"Spatial systems lipidomics reveals nonalcoholic fatty liver disease heterogeneity","volume":"90","author":"Soons","year":"2018","journal-title":"Anal. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1111\/apt.16066","article-title":"Circulating lipidomic alterations in obese and non-obese subjects with non-alcoholic fatty liver disease","volume":"52","author":"Jung","year":"2020","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_79","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_80","doi-asserted-by":"crossref","first-page":"e132158","DOI":"10.1172\/jci.insight.132158","article-title":"Hydroxysteroid 17-\u03b2 dehydrogenase 13 variant increases phospholipids and protects against fibrosis in nonalcoholic fatty liver disease","volume":"5","author":"Luukkonen","year":"2020","journal-title":"JCI Insight"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.freeradbiomed.2021.06.024","article-title":"Ethnicity-specific alterations of plasma and hepatic lipidomic profiles are related to high NAFLD rate and severity in Hispanic Americans, a pilot study","volume":"172","author":"Mazi","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_82","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_83","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_84","doi-asserted-by":"crossref","unstructured":"Perez-Diaz-del-Campo, N., Riezu-Boj, J.I., Marin-Alejandre, B.A., Monreal, J.I., Elorz, M., Herrero, J.I., Benito-Boillos, A., Milagro, F.I., Tur, J.A., and Abete, I. (2021). Three Different Genetic Risk Scores Based on Fatty Liver Index, Magnetic Resonance Imaging and Lipidomic for a Nutrigenetic Personalized Management of NAFLD: The Fatty Liver in Obesity Study. Diagnostics, 11.","DOI":"10.21203\/rs.3.rs-333145\/v1"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1111\/hepr.13528","article-title":"Metabolomic\/lipidomic-based analysis of plasma to diagnose hepatocellular ballooning in patients with non-alcoholic fatty liver disease: A multicenter study","volume":"50","author":"Ogawa","year":"2020","journal-title":"Hepatol. Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.hbpd.2021.05.008","article-title":"LC-MS-based lipidomic analysis in distinguishing patients with nonalcoholic steatohepatitis from nonalcoholic fatty liver","volume":"20","author":"Wang","year":"2021","journal-title":"Hepatobiliary Pancreat. Dis. Int."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Jambulingam, N., Forlano, R., Preston, B., Mullish, B.H., Portone, G., Baheer, Y., Yee, M., Goldin, R.D., Thursz, M.R., and Manousou, P. (2023). Metabolic Profile Reflects Stages of Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043563"},{"key":"ref_88","unstructured":"(2022, October 25). The Scarred Liver Project: A New Diagnostic Pathway to Detect Chronic Liver Disease across Primary and Secondary Care, NICE (n.d.). Available online: https:\/\/www.nice.org.uk\/sharedlearning\/the-scarred-liver-project."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1111\/apt.15192","article-title":"Derivation and validation of a cardiovascular risk score for prediction of major acute cardiovascular events in non-alcoholic fatty liver disease; the importance of an elevated mean platelet volume","volume":"49","author":"Abeles","year":"2019","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"14200","DOI":"10.1038\/s41598-018-31865-w","article-title":"Characterization of different fat depots in NAFLD using inflammation-associated proteome, lipidome and metabolome","volume":"8","author":"Lovric","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Preuss, C., Jelenik, T., B\u00f3dis, K., M\u00fcssig, K., Burkart, V., Szendroedi, J., Roden, M., and Markgraf, D.F. (2019). A New Targeted Lipidomics Approach Reveals Lipid Droplets in Liver, Muscle and Heart as a Repository for Diacylglycerol and Ceramide Species in Non-Alcoholic Fatty Liver. Cells, 8.","DOI":"10.3390\/cells8030277"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1016\/j.clnu.2017.08.031","article-title":"Omega-3 PUFA modulate lipogenesis, ER stress, and mitochondrial dysfunction markers in NASH\u2014Proteomic and lipidomic insight","volume":"37","author":"Okada","year":"2018","journal-title":"Clin. Nutr."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s12986-018-0288-5","article-title":"Changes in lysophospholipids and liver status after weight loss: The RESMENA study","volume":"15","author":"Cantero","year":"2018","journal-title":"Nutr. Metab."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.semcancer.2022.02.004","article-title":"The altered lipidome of hepatocellular carcinoma","volume":"86","author":"Tan","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s40880-018-0301-4","article-title":"Lipid metabolism reprogramming and its potential targets in cancer","volume":"38","author":"Cheng","year":"2018","journal-title":"Cancer Commun."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1002\/hep.31391","article-title":"Lipid Remodeling in Hepatocyte Proliferation and Hepatocellular Carcinoma","volume":"73","author":"Hall","year":"2021","journal-title":"Hepatology"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.tibs.2015.12.001","article-title":"The Warburg effect: How does it benefit cancer cells?","volume":"41","author":"Liberti","year":"2016","journal-title":"Trends Biochem. Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1002\/bies.201300084","article-title":"The Warburg effect then and now: From cancer to inflammatory diseases","volume":"35","year":"2013","journal-title":"Bioessays"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"8222","DOI":"10.1002\/cam4.4317","article-title":"Identification of a glycolysis-related gene signature for survival prediction of ovarian cancer patients","volume":"10","author":"Zhang","year":"2021","journal-title":"Cancer Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1053\/j.gastro.2013.01.054","article-title":"Integrated metabolite and gene expression profiles identify lipid biomarkers associated with progression of hepatocellular carcinoma and patient outcomes","volume":"144","author":"Budhu","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nrc3398","article-title":"Ceramide-orchestrated signalling in cancer cells","volume":"13","author":"Morad","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"(2021). Global Epidemiology of NAFLD-Related HCC: Trends, Predictions, Risk Factors and Prevention. Nat. Rev. Gastroenterol. Hepatol., 18, 223\u2013238.","DOI":"10.1038\/s41575-020-00381-6"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1159\/000525911","article-title":"Discriminatory Changes in Circulating Metabolites as a Predictor of Hepatocellular Cancer in Patients with Metabolic (Dysfunction) Associated Fatty Liver Disease","volume":"12","author":"Lu","year":"2023","journal-title":"Liver Cancer"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"103661","DOI":"10.1016\/j.ebiom.2021.103661","article-title":"The altered serum lipidome and its diagnostic potential for Non-Alcoholic Fatty Liver (NAFL)-associated hepatocellular carcinoma","volume":"73","author":"Lewinska","year":"2021","journal-title":"eBioMedicine"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1111\/j.1742-7843.2007.00199.x","article-title":"Chemosensitivity Determinants of Irinotecan Hydrochloride in Hepatocellular Carcinoma Cell Lines","volume":"102","author":"Takahata","year":"2008","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1177\/107327480301000207","article-title":"Overcoming Multidrug Resistance in Cancer: An Update on the Clinical Strategy of Inhibiting P-Glycoprotein","volume":"10","author":"Thomas","year":"2003","journal-title":"Cancer Control"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Simon, J., Ouro, A., Ala-Ibanibo, L., Presa, N., Delgado, T.C., and Mart\u00ednez-Chantar, M.L. (2020). Sphingolipids in Non-Alcoholic Fatty Liver Disease and Hepatocellular Carcinoma: Ceramide Turnover. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010040"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/S0014-5793(98)00744-3","article-title":"The multidrug resistance modulator SDZ PSC 833 is a potent activator of cellular ceramide formation","volume":"431","author":"Cabot","year":"1998","journal-title":"FEBS Lett."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/8\/1992\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:20:11Z","timestamp":1760124011000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/8\/1992"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,20]]},"references-count":108,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["nu15081992"],"URL":"https:\/\/doi.org\/10.3390\/nu15081992","relation":{},"ISSN":["2072-6643"],"issn-type":[{"type":"electronic","value":"2072-6643"}],"subject":[],"published":{"date-parts":[[2023,4,20]]}}}