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fatty liver disease (NAFLD) is a condition in which excess fat builds up in the liver. To date, there is a lack of knowledge about the subtype of lipid structures affected in the early stages of NAFLD. The aim of this study was to analyze serum and liver lipid moieties, specifically unsaturations and carbonyls, by nuclear magnetic resonance (NMR) in a subclinical Wistar rat model of NAFLD for detecting early alterations and potential sex dimorphisms. Twelve weeks of a high-fat diet (HFD) induced fat accumulation in the liver to a similar extent in male and female Wistar rats. In addition to total liver fat accumulation, Wistar rats showed a shift in lipid subtype composition. HFD rats displayed increased lipid carbonyls in both liver and serum, and decreased in unsaturated fatty acids (UFAs) and polyunsaturated fatty acids (PUFAs), with a much stronger effect in male than female animals. Our results revealed that the change in fat was not only quantitative but also qualitative, with dramatic shifts in relevant lipid structures. Finally, we compared the results found in Wistar rats with an analysis in a human patient cohort of extreme obesity. For the first time to our knowledge, lipid carbonyl levels and lipoproteins profiles were analyzed in the context of subclinical NAFLD. The association found between lipid carbonyls and alanine aminotransferase (ALT) in a human cohort of extremely obese individuals further supports the potential role of lipid moieties as biomarkers of early NAFLD.<\/jats:p>","DOI":"10.3390\/antiox12101808","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T05:55:54Z","timestamp":1695880554000},"page":"1808","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Altered Lipid Moieties and Carbonyls in a Wistar Rat Dietary Model of Subclinical Fatty Liver: Potential Sex-Specific Biomarkers of Early Fatty Liver Disease?"],"prefix":"10.3390","volume":"12","author":[{"given":"Mar\u00eda","family":"Mart\u00edn-Grau","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Valencia, 46010 Valencia, Spain"},{"name":"University Clinical Hospital of Valencia Research Foundation (INCLIVA), 46010 Valencia, 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Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4606-1792","authenticated-orcid":false,"given":"Consuelo","family":"Borr\u00e1s","sequence":"additional","affiliation":[{"name":"University Clinical Hospital of Valencia Research Foundation (INCLIVA), 46010 Valencia, Spain"},{"name":"Department of Physiology, University of Valencia, 46010 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9303-483X","authenticated-orcid":false,"given":"Serena","family":"Pisoni","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Valencia, 46010 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0859-4600","authenticated-orcid":false,"given":"Sabrina","family":"Maestrini","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Istituto Auxologico Italiano IRCCS, 20145 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disease (NAFLD) and nonalcoholic steatohepatitis (NASH): A systematic review","volume":"77","author":"Younossi","year":"2023","journal-title":"Hepatology"},{"key":"ref_2","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_3","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_4","doi-asserted-by":"crossref","first-page":"9547613","DOI":"10.1155\/2018\/9547613","article-title":"Role of Oxidative Stress in Pathophysiology of Nonalcoholic Fatty Liver Disease","volume":"2018","author":"Masarone","year":"2018","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"370","DOI":"10.2183\/pjab.89.370","article-title":"The biological significance of \u03c9-oxidation of fatty acids","volume":"89","author":"Miura","year":"2013","journal-title":"Proc. JPN Acad. Ser. B Phys. Biol. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zhang, X., Gao, T., Deng, S., Shang, L., Chen, X., Chen, K., Li, P., Cui, X., and Zeng, J. (2021). Fasting induces hepatic lipid accumulation by stimulating peroxisomal dicarboxylic acid oxidation. J. Biol. Chem., 296.","DOI":"10.1016\/j.jbc.2021.100622"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"360438","DOI":"10.1155\/2014\/360438","article-title":"Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal","volume":"2014","author":"Ayala","year":"2014","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.cbi.2014.12.028","article-title":"Oxidative and reductive metabolism of lipid-peroxidation derived carbonyls","volume":"234","author":"Singh","year":"2015","journal-title":"Chem. Biol. Interact."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.chemphyslip.2019.03.011","article-title":"Biological effect of protein modifications by lipid peroxidation products","volume":"221","author":"Skrzydlewska","year":"2019","journal-title":"Chem. Phys. Lipids"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Arroyave-Ospina, J.C., Wu, Z., Geng, Y., and Moshage, H. (2021). Role of Oxidative Stress in the Pathogenesis of Non-Alcoholic Fatty Liver Disease: Implications for Prevention and Therapy. Antioxidants, 10.","DOI":"10.3390\/antiox10020174"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.freeradbiomed.2020.02.025","article-title":"Role of oxidative stress in the pathogenesis of nonalcoholic fatty liver disease","volume":"152","author":"Chen","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8263","DOI":"10.3748\/wjg.v23.i47.8263","article-title":"Clinical epidemiology and disease burden of nonalcoholic fatty liver disease","volume":"23","author":"Perumpail","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Lonardo, A., Mantovani, A., Lugari, S., and Targher, G. (2019). NAFLD in Some Common Endocrine Diseases: Prevalence, Pathophysiology, and Principles of Diagnosis and Management. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20112841"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.bbadis.2013.05.006","article-title":"Sex dimorphism and depot differences in adipose tissue function","volume":"1842","author":"White","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Della Torre, S. (2021). Beyond the X Factor: Relevance of Sex Hormones in NAFLD Pathophysiology. Cells, 10.","DOI":"10.3390\/cells10092502"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.biochi.2016.11.009","article-title":"PPARs and nonalcoholic fatty liver disease","volume":"136","author":"Liss","year":"2017","journal-title":"Biochimie"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.clnu.2017.01.006","article-title":"Non-alcoholic fatty liver disease and its treatment with n-3 polyunsaturated fatty acids","volume":"37","author":"Calder","year":"2018","journal-title":"Clin. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1002\/hep4.1906","article-title":"Effect of Omega-3 Polyunsaturated Fatty Acids on Lipid Metabolism in Patients With Metabolic Syndrome and NAFLD","volume":"6","author":"Kosek","year":"2022","journal-title":"Hepatol. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4084","DOI":"10.1038\/s41467-020-17915-w","article-title":"Scavenging of reactive dicarbonyls with 2-hydroxybenzylamine reduces atherosclerosis in hypercholesterolemic Ldlr\u2212\/\u2212 mice","volume":"11","author":"Tao","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8426","DOI":"10.1158\/0008-5472.CAN-10-1498","article-title":"Metabolic aggressiveness in benign meningiomas with chromosomal instabilities","volume":"70","author":"Morales","year":"2010","journal-title":"Cancer Res."},{"key":"ref_21","first-page":"111","article-title":"Metabolic profile of chronic liver disease by NMR spectroscopy of human biopsies","volume":"27","author":"Morales","year":"2011","journal-title":"Int. J. Mol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"367","DOI":"10.3389\/fendo.2018.00367","article-title":"Analysis of Predictive Equations for Estimating Resting Energy Expenditure in a Large Cohort of Morbidly Obese Patients","volume":"9","author":"Cancello","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1039\/b910205a","article-title":"High-throughput serum NMR metabonomics for cost-effective holistic studies on systemic metabolism","volume":"134","author":"Soininen","year":"2009","journal-title":"Analyst"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Schiffrin, M., Winkler, C., Quignodon, L., Naldi, A., Tr\u00f6tzm\u00fcller, M., K\u00f6feler, H., Henry, H., Parini, P., Desvergne, B., and Gilardi, F. (2021). Sex Dimorphism of Nonalcoholic Fatty Liver Disease (NAFLD) in Pparg-Null Mice. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22189969"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Perla, F.M., Prelati, M., Lavorato, M., Visicchio, D., and Anania, C. (2017). The Role of Lipid and Lipoprotein Metabolism in Non-Alcoholic Fatty Liver Disease. Children, 4.","DOI":"10.3390\/children4060046"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"101238","DOI":"10.1016\/j.molmet.2021.101238","article-title":"Metabolic-associated fatty liver disease and lipoprotein metabolism","volume":"50","author":"Heeren","year":"2021","journal-title":"Mol. Metab."},{"key":"ref_27","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_28","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_29","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_30","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.bbadis.2009.09.007","article-title":"Direct antioxidant and protective effect of estradiol on isolated mitochondria","volume":"1802","author":"Gambini","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Yang, M., Ma, F., and Guan, M. (2021). Role of Steroid Hormones in the Pathogenesis of Nonalcoholic Fatty Liver Disease. Metabolites, 11.","DOI":"10.3390\/metabo11050320"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/12\/10\/1808\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:00:24Z","timestamp":1760130024000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/12\/10\/1808"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,28]]},"references-count":31,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["antiox12101808"],"URL":"https:\/\/doi.org\/10.3390\/antiox12101808","relation":{},"ISSN":["2076-3921"],"issn-type":[{"type":"electronic","value":"2076-3921"}],"subject":[],"published":{"date-parts":[[2023,9,28]]}}}