{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T11:09:21Z","timestamp":1773745761834,"version":"3.50.1"},"reference-count":24,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T00:00:00Z","timestamp":1692921600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Fatty liver is common in obesity as well as in partial lipodystrophy (PL) syndromes, characterized by deficient adipose tissue. Insulin resistance is key to fatty liver pathogenesis in both entities. We aimed to compare the contributions of insulin resistance and adipose tissue to hepatic steatosis in PL and non\u2010syndromic, obesity\u2010associated non\u2010alcoholic fatty liver disease (NS\u2010NAFLD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a cross\u2010sectional comparison of people with NS\u2010NAFLD (<jats:italic>N<\/jats:italic>\u2009=\u200973) and PL (<jats:italic>N<\/jats:italic>\u2009=\u200927), liver fat was measured by FibroScan<jats:sup>\u00ae<\/jats:sup> controlled attenuation parameter (CAP) and insulin resistance by HOMA\u2010IR, Adipo\u2010IR, and NMR\u2010based LP\u2010IR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Insulin resistance was greater in PL versus NS\u2010NAFLD by HOMA\u2010IR (<jats:italic>p<\/jats:italic>\u2009=\u20090.005), Adipo\u2010IR (<jats:italic>p<\/jats:italic>\u2009=\u20090.01) and LP\u2010IR (<jats:italic>p<\/jats:italic>\u2009=\u20090.05) while liver fat was comparable (304 vs. 324\u2009dB\/m, <jats:italic>p<\/jats:italic>\u2009=\u20090.12). Liver fat correlated with HOMA\u2010IR in both groups, but CAP values were lower by 32\u2009dB\/m in PL compared with NS\u2010NAFLD for any given HOMA\u2010IR. In contrast, Adipo\u2010IR and LP\u2010IR correlated with CAP only in the NS\u2010NAFLD group, suggesting different pathways for fat accumulation. Plasma free fatty acids, reflecting substrate input from the adipose tissue, were comparable between groups. However, the levels of \u03b2\u2010hydroxybutyrate, a marker of \u03b2\u2010oxidation, and large triglyceride\u2010rich lipoprotein particles, a marker of VLDL secretion, were both higher in PL (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001 for both).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Liver fat content was comparable in subjects with PL\u2010associated NAFLD and NS\u2010NAFLD, despite worse insulin resistance in partial lipodystrophy. Our data demonstrate higher triglyceride oxidation and export in PL, suggesting a compensatory shift of fat from liver storage into the circulation that does not occur in NS\u2010NAFLD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15707","type":"journal-article","created":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T08:33:29Z","timestamp":1692952409000},"page":"2692-2700","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Divergent pathways of liver fat accumulation, oxidation, and secretion in lipodystrophy versus obesity\u2010associated <scp>NAFLD<\/scp>"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4289-0887","authenticated-orcid":false,"given":"Rachael J.","family":"Klein","sequence":"first","affiliation":[{"name":"Section on Translational Diabetes and Metabolic Syndromes, Diabetes, Endocrinology and Obesity Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7159-8181","authenticated-orcid":false,"given":"Gracia M.","family":"Viana\u00a0Rodriguez","sequence":"additional","affiliation":[{"name":"Liver &amp; Energy Metabolism Section, Liver Diseases Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7549-8216","authenticated-orcid":false,"given":"Yaron","family":"Rotman","sequence":"additional","affiliation":[{"name":"Liver &amp; Energy Metabolism Section, Liver Diseases Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2589-7382","authenticated-orcid":false,"given":"Rebecca J.","family":"Brown","sequence":"additional","affiliation":[{"name":"Section on Translational Diabetes and Metabolic Syndromes, Diabetes, Endocrinology and Obesity Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,8,25]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-021-00523-4"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28431"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.12.009"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.1.7"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI134165"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.02.007"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-2466"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00063.2017"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1658"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.18.7.1046"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1089\/met.2014.0050"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-00047"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23621"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2020.02.005"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2015.10.024"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI135431"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cld.1183"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/osp4.319"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2011.04.007"},{"key":"e_1_2_12_21_1","first-page":"2347","article-title":"FoxO1 mediates insulin\u2010dependent regulation of hepatic VLDL production in mice","volume":"118","author":"Kamagate A","year":"2008","journal-title":"J Clin Investig"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2021.101261"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac660"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/86.2.285"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2022.03.004"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.15707","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,3]],"date-time":"2024-01-03T19:14:42Z","timestamp":1704309282000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.15707"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,25]]},"references-count":24,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["10.1111\/liv.15707"],"URL":"https:\/\/doi.org\/10.1111\/liv.15707","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,25]]},"assertion":[{"value":"2023-06-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}