{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T02:59:09Z","timestamp":1785466749018,"version":"3.56.0"},"reference-count":41,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T00:00:00Z","timestamp":1665014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"German Ministry of Education and Research, the State of Brandenburg","doi-asserted-by":"publisher","award":["82DZD00302"],"award-info":[{"award-number":["82DZD00302"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in the liver. Various mechanisms such as an increased uptake in fatty acids or de novo synthesis contribute to the development of steatosis and progression to more severe stages. Furthermore, it has been shown that impaired lipophagy, the degradation of lipids by autophagic processes, contributes to NAFLD. Through an unbiased lipidome analysis of mouse livers in a genetic model of impaired lipophagy, we aimed to determine the resulting alterations in the lipidome. Observed changes overlap with those of the human disease. Overall, the entire lipid content and in particular the triacylglycerol concentration increased under conditions of impaired lipophagy. In addition, we detected a reduction in long-chain polyunsaturated fatty acids (PUFAs) and an increased ratio of n-6 PUFAs to n-3 PUFAs, which was due to the depletion of n-3 PUFAs. Although the abundance of major phospholipid classes was reduced, the ratio of phosphatidylcholines to phosphatidylethanolamines was not affected. In conclusion, this study demonstrates that impaired lipophagy contributes to the pathology of NAFLD and is associated with an altered lipid profile. However, the lipid pattern does not appear to be specific for lipophagic alterations, as it resembles mainly that described in relation to fatty liver disease.<\/jats:p>","DOI":"10.3390\/ijms231911863","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T23:39:31Z","timestamp":1665272371000},"page":"11863","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Alterations of Lipid Profile in Livers with Impaired Lipophagy"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3441-9200","authenticated-orcid":false,"given":"Wenke","family":"Jonas","sequence":"first","affiliation":[{"name":"Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany"},{"name":"German Center for Diabetes Research, 85764 M\u00fcnchen-Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Schwerbel","sequence":"additional","affiliation":[{"name":"Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany"},{"name":"German Center for Diabetes Research, 85764 M\u00fcnchen-Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Zellner","sequence":"additional","affiliation":[{"name":"Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany"},{"name":"German Center for Diabetes Research, 85764 M\u00fcnchen-Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6459-7318","authenticated-orcid":false,"given":"Markus","family":"J\u00e4hnert","sequence":"additional","affiliation":[{"name":"Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany"},{"name":"German Center for Diabetes Research, 85764 M\u00fcnchen-Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9791-783X","authenticated-orcid":false,"given":"Pascal","family":"Gottmann","sequence":"additional","affiliation":[{"name":"Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany"},{"name":"German Center for Diabetes Research, 85764 M\u00fcnchen-Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4113-4377","authenticated-orcid":false,"given":"Annette","family":"Sch\u00fcrmann","sequence":"additional","affiliation":[{"name":"Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany"},{"name":"German Center for Diabetes Research, 85764 M\u00fcnchen-Neuherberg, Germany"},{"name":"University of Potsdam, Institute of Nutritional Sciences, 14558 Nuthetal, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,6]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.jhep.2018.05.036","article-title":"Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016\u20132030","volume":"69","author":"Estes","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/S1665-2681(19)30879-8","article-title":"The prevalence of nonalcoholic fatty liver disease in the Americas","volume":"13","author":"Arrese","year":"2014","journal-title":"Ann. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"001","DOI":"10.1055\/s-0038-1627456","article-title":"Nonalcoholic Fatty Liver Disease in Children","volume":"38","author":"Mann","year":"2018","journal-title":"Semin. Liver Dis."},{"key":"ref_6","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_7","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1053\/j.gastro.2011.04.038","article-title":"Functions of Autophagy in Hepatic and Pancreatic Physiology and Disease","volume":"140","author":"Czaja","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1038\/nature07976","article-title":"Autophagy regulates lipid metabolism","volume":"458","author":"Singh","year":"2009","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/978-3-642-14426-4_4","article-title":"Autophagy and Regulation of Lipid Metabolism","volume":"52","author":"Singh","year":"2010","journal-title":"Sens. Metab. Control. Energy Balance"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1042\/CS20030326","article-title":"Increase in long-chain polyunsaturated fatty acid n\u22126\/n\u22123 ratio in relation to hepatic steatosis in patients with non-alcoholic fatty liver disease","volume":"106","author":"Araya","year":"2004","journal-title":"Clin. Sci."},{"key":"ref_11","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_12","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_13","doi-asserted-by":"crossref","first-page":"3099","DOI":"10.1093\/hmg\/ddy217","article-title":"A collective diabetes cross in combination with a computational framework to dissect the genetics of human obesity and Type 2 diabetes","volume":"27","author":"Vogel","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.jhep.2020.04.031","article-title":"Immunity-related GTPase induces lipophagy to prevent excess hepatic lipid accumulation","volume":"73","author":"Schwerbel","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_15","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_16","doi-asserted-by":"crossref","first-page":"100104","DOI":"10.1016\/j.jlr.2021.100104","article-title":"Nonalcoholic fatty liver disease stratification by liver lipidomics","volume":"62","author":"Vvedenskaya","year":"2021","journal-title":"J. Lipid Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1016\/j.freeradbiomed.2004.06.033","article-title":"Oxidative stress and depletion of hepatic long-chain polyunsaturated fatty acids may contribute to nonalcoholic fatty liver disease","volume":"37","author":"Videla","year":"2004","journal-title":"Free Radic. Biol. Med."},{"key":"ref_18","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_19","doi-asserted-by":"crossref","first-page":"248","DOI":"10.3389\/fcell.2019.00248","article-title":"Fatty Liver Due to Increased de novo Lipogenesis: Alterations in the Hepatic Peroxisomal Proteome","volume":"7","author":"Knebel","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_20","first-page":"G865","article-title":"Molecular mechanism for polyunsaturated fatty acid regulation of gene transcription","volume":"281","author":"Clarke","year":"2001","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.plefa.2015.04.002","article-title":"Reduction in the desaturation capacity of the liver in mice subjected to high fat diet: Relation to LCPUFA depletion in liver and extrahepatic tissues","volume":"98","author":"Valenzuela","year":"2015","journal-title":"Prostaglandins, Leukot. Essent. Fat. Acids"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1016\/j.bbamem.2017.04.006","article-title":"The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease","volume":"1859","author":"Kennelly","year":"2017","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.cmet.2006.03.007","article-title":"The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis","volume":"3","author":"Li","year":"2006","journal-title":"Cell Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/bs.ircmb.2015.10.001","article-title":"Phosphatidylethanolamine Metabolism in Health and Disease","volume":"321","author":"Calzada","year":"2015","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"436","DOI":"10.4254\/wjh.v12.i8.436","article-title":"Lipidomics in non-alcoholic fatty liver disease","volume":"12","author":"Kartsoli","year":"2020","journal-title":"World J. Hepatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1002\/hep.21788","article-title":"Good fat\/bad fat","volume":"45","author":"McClain","year":"2007","journal-title":"Hepatology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.jhep.2007.09.009","article-title":"Nutritional assessment and hepatic fatty acid composition in non-alcoholic fatty liver disease (NAFLD): A cross-sectional study","volume":"48","author":"Allard","year":"2008","journal-title":"J. Hepatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1111\/liv.12685","article-title":"Characteristics of hepatic fatty acid compositions in patients with nonalcoholic steatohepatitis","volume":"35","author":"Yamada","year":"2014","journal-title":"Liver Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"601627","DOI":"10.3389\/fendo.2020.601627","article-title":"The Role of Lipophagy in the Development and Treatment of Non-Alcoholic Fatty Liver Disease","volume":"11","author":"Grefhorst","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.bbrc.2011.08.012","article-title":"Hepatic steatosis inhibits autophagic proteolysis via impairment of autophagosomal acidification and cathepsin expression","volume":"412","author":"Inami","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1016\/j.jhep.2016.06.029","article-title":"Variants in the autophagy-related gene IRGM confer susceptibility to non-alcoholic fatty liver disease by modulating lipophagy","volume":"65","author":"Lin","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"850","DOI":"10.3389\/fphys.2020.00850","article-title":"Lipophagy Impairment Is Associated With Disease Progression in NAFLD","volume":"11","author":"Carotti","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"14890","DOI":"10.1074\/jbc.M010286200","article-title":"Palmitate-induced Apoptosis Can Occur through a Ceramide-independent Pathway","volume":"276","author":"Listenberger","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_34","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":"2013","journal-title":"Metabolism"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1002\/hep.26672","article-title":"Nonalcoholic fatty liver disease, hepatic insulin resistance, and type 2 Diabetes","volume":"59","author":"Birkenfeld","year":"2013","journal-title":"Hepatology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.yexcr.2017.03.032","article-title":"Palmitate mediated diacylglycerol accumulation causes endoplasmic reticulum stress, Plin2 degradation, and cell death in H9C2 cardiomyoblasts","volume":"354","author":"Akoumi","year":"2017","journal-title":"Exp. Cell Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1016\/j.nut.2015.05.022","article-title":"\u03c9-3 Fatty acids reverse lipotoxity through induction of autophagy in nonalcoholic fatty liver disease","volume":"31","author":"Chen","year":"2015","journal-title":"Nutrition"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.pep.2008.08.002","article-title":"Wheat germ cell-free translation, purification, and assembly of a functional human stearoyl-CoA desaturase complex","volume":"62","author":"Goren","year":"2008","journal-title":"Protein Expr. Purif."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.bbrc.2005.05.013","article-title":"Characterization of HSCD5, a novel human stearoyl-CoA desaturase unique to primates","volume":"332","author":"Wang","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1042\/BJ20041554","article-title":"Characterization of human SCD2, an oligomeric desaturase with improved stability and enzyme activity by cross-linking in intact cells","volume":"388","author":"Zhang","year":"2005","journal-title":"Biochem. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11863\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:47:17Z","timestamp":1760143637000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11863"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,6]]},"references-count":41,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijms231911863"],"URL":"https:\/\/doi.org\/10.3390\/ijms231911863","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,6]]}}}