{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T11:15:05Z","timestamp":1794050105514,"version":"4.8.0"},"reference-count":45,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T00:00:00Z","timestamp":1711497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Detailed investigation of the lipidome remodeling upon normal weight conditions, obesity, or weight loss, as well as the influence of physical activity, can help to understand the mechanisms underlying dyslipidemia in metabolic conditions correlated to the emergence and progression of non-alcoholic fatty liver disease (NAFLD). C57BL\/6 male mice were fed a normal diet (ND) or a high-fat diet (HFD) for 20 weeks. Subgroups within the high-fat diet (HFD) group underwent different interventions: some engaged in exercise (HFDex), others were subjected to weight loss (WL) by changing from the HFD to ND, and some underwent a combination of weight loss and exercise (WLex) during the final 8 weeks of the 20-week feeding period. To support our understanding, not only tissue-specific lipid remodeling mechanisms but also the cross-talk between different tissues and their impact on the systemic regulation of lipid metabolism are essential. Exercise and weight loss-induced specific adaptations in the liver and visceral adipose tissue lipidomes of mice were explored by the UPLC\u2013TOF\u2013MS\/MS untargeted lipidomics methodology. Lipidomic signatures of ND and HFD-fed mice undergoing weight loss were compared with animals with and without physical exercise. Several lipid classes were identified as contributing factors in the discrimination of the groups by multivariate analysis models, such as glycerolipids, glycerophospholipids, sphingolipids, and fatty acids, with respect to liver samples, whereas triglycerides were the only lipid class identified in visceral adipose tissue. Lipids found to be dysregulated in HFD animals are related to well-established pathways involved in the biosynthesis of PC, PE, and TG metabolism. These show a reversing trend back to basic levels of ND when animals change to a normal diet after 12 weeks, whereas the impact of exercise, though in some cases it slightly enhances the reversing trend, is not clear.<\/jats:p>","DOI":"10.3390\/molecules29071494","type":"journal-article","created":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T12:41:57Z","timestamp":1711543317000},"page":"1494","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Lipidomic Analysis of Liver and Adipose Tissue in a High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Mice Model Reveals Alterations in Lipid Metabolism by Weight Loss and Aerobic Exercise"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2511-1236","authenticated-orcid":false,"given":"Thomai","family":"Mouskeftara","sequence":"first","affiliation":[{"name":"Laboratory of Forensic Medicine & Toxicology, Department of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"},{"name":"Biomic AUTh, Center for Interdisciplinary Research and Innovation (CIRI-AUTH), Balkan Center B1.4, 10th km Thessaloniki-Thermi Rd, P.O. Box 8318, 57001 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3642-7367","authenticated-orcid":false,"given":"Olga","family":"Deda","sequence":"additional","affiliation":[{"name":"Laboratory of Forensic Medicine & Toxicology, Department of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"},{"name":"Biomic AUTh, Center for Interdisciplinary Research and Innovation (CIRI-AUTH), Balkan Center B1.4, 10th km Thessaloniki-Thermi Rd, P.O. Box 8318, 57001 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9142-943X","authenticated-orcid":false,"given":"Grigorios","family":"Papadopoulos","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Str., 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7039-4223","authenticated-orcid":false,"given":"Antonios","family":"Chatzigeorgiou","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Str., 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1893-937X","authenticated-orcid":false,"given":"Helen","family":"Gika","sequence":"additional","affiliation":[{"name":"Laboratory of Forensic Medicine & Toxicology, Department of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"},{"name":"Biomic AUTh, Center for Interdisciplinary Research and Innovation (CIRI-AUTH), Balkan Center B1.4, 10th km Thessaloniki-Thermi Rd, P.O. Box 8318, 57001 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/s41575-021-00523-4","article-title":"Advancing the Global Public Health Agenda for NAFLD: A Consensus Statement","volume":"19","author":"Lazarus","year":"2022","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/s41577-021-00639-3","article-title":"Immune Cell-Mediated Features of Non-Alcoholic Steatohepatitis","volume":"22","author":"Huby","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.3350\/cmh.2022.0424","article-title":"Non-Alcoholic Fatty Liver Disease: Definition and Subtypes","volume":"29","author":"Han","year":"2023","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_4","first-page":"9338","article-title":"Role of Diet and Lifestyle Changes in Nonalcoholic Fatty Liver Disease","volume":"20","author":"Nseir","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_5","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_6","doi-asserted-by":"crossref","first-page":"100149","DOI":"10.1016\/j.metop.2021.100149","article-title":"Metabolic Causes and Consequences of Nonalcoholic Fatty Liver Disease (NAFLD)","volume":"12","author":"Zarghamravanbakhsh","year":"2021","journal-title":"Metab. Open"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1007\/s11883-022-01028-4","article-title":"Management of Dyslipidemia in Patients with Non-Alcoholic Fatty Liver Disease","volume":"24","author":"Martin","year":"2022","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1111\/jdi.13756","article-title":"Non-alcoholic Fatty Liver Disease and Type\u20092 Diabetes: An Update","volume":"13","author":"Lee","year":"2022","journal-title":"J. Diabetes Investig."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/S2468-1253(22)00375-2","article-title":"NAFLD Prevalence and Severity in Overweight and Obese Populations","volume":"8","author":"Francque","year":"2023","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Hsu, C.L., and Loomba, R. (2024). From NAFLD to MASLD: Implications of the New Nomenclature for Preclinical and Clinical Research. Nat. Metab., 1\u20133.","DOI":"10.1038\/s42255-024-00985-1"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Eng, J.M., and Estall, J.L. (2021). Diet-Induced Models of Non-Alcoholic Fatty Liver Disease: Food for Thought on Sugar, Fat, and Cholesterol. Cells, 10.","DOI":"10.3390\/cells10071805"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3248","DOI":"10.1210\/clinem\/dgab508","article-title":"Consuming Sucrose- or HFCS-Sweetened Beverages Increases Hepatic Lipid and Decreases Insulin Sensitivity in Adults","volume":"106","author":"Sigala","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.jhep.2018.01.019","article-title":"Fructose and Sugar: A Major Mediator of Nonalcoholic Fatty Liver Disease","volume":"68","author":"Jensen","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"155552","DOI":"10.1016\/j.metabol.2023.155552","article-title":"Integrated Omics Analysis for Characterization of the Contribution of High Fructose Corn Syrup to Non-Alcoholic Fatty Liver Disease in Obesity","volume":"144","author":"Papadopoulos","year":"2023","journal-title":"Metabolism"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1111\/dom.14569","article-title":"Weight Loss Interventions and Nonalcoholic Fatty Liver Disease: Optimizing Liver Outcomes","volume":"24","author":"Finer","year":"2022","journal-title":"Diabetes Obes. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1016\/j.jhep.2018.08.011","article-title":"Beneficial Effects of Lifestyle Intervention in Non-Obese Patients with Non-Alcoholic Fatty Liver Disease","volume":"69","author":"Wong","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_17","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_18","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.jhep.2005.06.008","article-title":"Effect of Changes on Body Weight and Lifestyle in Nonalcoholic Fatty Liver Disease","volume":"43","author":"Suzuki","year":"2005","journal-title":"J. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1136\/gut.2003.027581","article-title":"Modest Weight Loss and Physical Activity in Overweight Patients with Chronic Liver Disease Results in Sustained Improvements in Alanine Aminotransferase, Fasting Insulin, and Quality of Life","volume":"53","author":"Hickman","year":"2004","journal-title":"Gut"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Shama, S., Jang, H., Wang, X., Zhang, Y., Shahin, N.N., Motawi, T.K., Kim, S., Gawrieh, S., and Liu, W. (2023). Phosphatidylethanolamines Are Associated with Nonalcoholic Fatty Liver Disease (NAFLD) in Obese Adults and Induce Liver Cell Metabolic Perturbations and Hepatic Stellate Cell Activation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021034"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Knebel, B., Fahlbusch, P., Dille, M., Wahlers, N., Hartwig, S., Jacob, S., Kettel, U., Schiller, M., Herebian, D., and Koellmer, C. (2019). Fatty Liver Due to Increased de Novo Lipogenesis: Alterations in the Hepatic Peroxisomal Proteome. Front. Cell Dev. Biol., 7.","DOI":"10.3389\/fcell.2019.00248"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ziolkowska, S., Binienda, A., Jab\u0142kowski, M., Szemraj, J., and Czarny, P. (2021). The Interplay between Insulin Resistance, Inflammation, Oxidative Stress, Base Excision Repair and Metabolic Syndrome in Nonalcoholic Fatty Liver Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222011128"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12986-022-00644-w","article-title":"Effects of Exercise on High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease and Lipid Metabolism in ApoE Knockout Mice","volume":"19","author":"Huang","year":"2022","journal-title":"Nutr. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"H1100","DOI":"10.1152\/ajpheart.00697.2019","article-title":"Guidelines for Animal Exercise and Training Protocols for Cardiovascular Studies","volume":"318","author":"Poole","year":"2020","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"100331","DOI":"10.1016\/j.xpro.2021.100331","article-title":"Monitoring Daytime Differences in Moderate Intensity Exercise Capacity Using Treadmill Test and Muscle Dissection","volume":"2","author":"Adamovich","year":"2021","journal-title":"STAR Protoc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1161\/CIRCRESAHA.122.320247","article-title":"Animal Models of Exercise from Rodents to Pythons","volume":"130","author":"Hastings","year":"2022","journal-title":"Circ. Res."},{"key":"ref_27","unstructured":"PubMed (2023, November 19). Physical Activity Protocols in Non-Alcoholic Fatty Liver Disease Management: A Systematic Review of Randomized Clinical Trials and Animal Models, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/37510432\/."},{"key":"ref_28","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 BBA Biomembr."},{"key":"ref_29","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_30","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_31","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1007\/s00125-013-2981-2","article-title":"Prediction of Non-Alcoholic Fatty-Liver Disease and Liver Fat Content by Serum Molecular Lipids","volume":"56","author":"Kotronen","year":"2013","journal-title":"Diabetologia"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/s41575-021-00502-9","article-title":"Metabolomics and Lipidomics in NAFLD: Biomarkers and Non-Invasive Diagnostic Tests","volume":"18","author":"Masoodi","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1002\/hep.23229","article-title":"The Plasma Lipidomic Signature of Nonalcoholic Steatohepatitis","volume":"50","author":"Puri","year":"2009","journal-title":"Hepatology"},{"key":"ref_34","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_35","first-page":"e710290","article-title":"Five Decades with Polyunsaturated Fatty Acids: Chemical Synthesis, Enzymatic Formation, Lipid Peroxidation and Its Biological Effects","volume":"2013","year":"2013","journal-title":"J. Lipids"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1038\/oby.2009.379","article-title":"Decreased Liver Fatty Acid Delta-6 and Delta-5 Desaturase Activity in Obese Patients","volume":"18","author":"Araya","year":"2010","journal-title":"Obesity"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1093\/ajcn\/nqac150","article-title":"Associations of Serum N-3 and n-6 Polyunsaturated Fatty Acids with Prevalence and Incidence of Nonalcoholic Fatty Liver Disease","volume":"116","author":"Tuomainen","year":"2022","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1053\/j.gastro.2021.05.008","article-title":"Associations Among Adipose Tissue Immunology, Inflammation, Exosomes and Insulin Sensitivity in People with Obesity and Nonalcoholic Fatty Liver Disease","volume":"161","author":"Fuchs","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e13695","DOI":"10.1111\/eci.13695","article-title":"Adipose Tissue Insulin Resistance and Lipidome Alterations as the Characterizing Factors of Non-alcoholic Steatohepatitis","volume":"52","author":"Guerra","year":"2022","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/j.jhep.2019.06.031","article-title":"Crosstalk between Adipose Tissue Insulin Resistance and Liver Macrophages in Non-Alcoholic Fatty Liver Disease","volume":"71","author":"Rosso","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"100407","DOI":"10.1016\/j.xcrm.2021.100407","article-title":"AdipoAtlas: A Reference Lipidome for Human White Adipose Tissue","volume":"2","author":"Lange","year":"2021","journal-title":"Cell Rep. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1042\/EBC20200067","article-title":"Mammalian Lipids: Structure, Synthesis and Function","volume":"65","author":"Cockcroft","year":"2021","journal-title":"Essays Biochem."},{"key":"ref_43","first-page":"61","article-title":"Women Have Lower Risk of Nonalcoholic Fatty Liver Disease but Higher Risk of Progression vs Men: A Systematic Review and Meta-Analysis","volume":"19","author":"Balakrishnan","year":"2021","journal-title":"Clin. Gastroenterol. Hepatol. Off. Clin. Pract. J. Am. Gastroenterol. Assoc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.aca.2018.02.053","article-title":"Evaluation of Batch Effect Elimination Using Quality Control Replicates in LC-MS Metabolite Profiling","volume":"1019","author":"Vento","year":"2018","journal-title":"Anal. Chim. Acta"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"6257","DOI":"10.1021\/acs.analchem.7b01259","article-title":"Lipostar, a Comprehensive Platform-Neutral Cheminformatics Tool for Lipidomics","volume":"89","author":"Goracci","year":"2017","journal-title":"Anal. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/7\/1494\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:19:29Z","timestamp":1760105969000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/7\/1494"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,27]]},"references-count":45,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["molecules29071494"],"URL":"https:\/\/doi.org\/10.3390\/molecules29071494","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,27]]}}}