{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T19:09:49Z","timestamp":1782846589133,"version":"3.54.5"},"reference-count":0,"publisher":"American Society for Clinical Investigation","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"crossref","award":["R01DK141041"],"award-info":[{"award-number":["R01DK141041"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"crossref","award":["R01DK112304"],"award-info":[{"award-number":["R01DK112304"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"crossref","award":["R56DK133997"],"award-info":[{"award-number":["R56DK133997"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"crossref","award":["K08DK124679"],"award-info":[{"award-number":["K08DK124679"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"crossref","award":["P30DK098722"],"award-info":[{"award-number":["P30DK098722"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"crossref","award":["5T32DK007418"],"award-info":[{"award-number":["5T32DK007418"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"crossref","award":["P30 AI027763"],"award-info":[{"award-number":["P30 AI027763"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000867","name":"Robert Wood Johnson Foundation","doi-asserted-by":"crossref","award":["Harold Amos Medical Faculty Development Program"],"award-info":[{"award-number":["Harold Amos Medical Faculty Development Program"]}],"id":[{"id":"10.13039\/100000867","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    <jats:bold>BACKGROUND.<\/jats:bold>\n                    Despite antiretroviral therapy (ART), people with HIV (PWH) are at heightened risk for insulin resistance (IR) and type 2 diabetes (T2D). Subcutaneous adipose tissue (SAT) fibrosis contributes to metabolic disease, but its role in IR among PWH is unknown. We investigated the relationship between SAT fibrosis and IR in PWH, along with transcriptional signatures to distinguish it from SAT fibrosis due to obesity.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>METHODS.<\/jats:bold>\n                    We analyzed body composition and SAT fibrosis (hydroxyproline) in 46 PWH and 74 people without HIV (PWoH), excluding individuals with T2D. We examined fibrosis-related gene transcription in the SAT using a targeted panel and measured plasma endotrophin, a marker of extracellular matrix (ECM) remodeling.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>RESULTS.<\/jats:bold>\n                    PWH had substantially more SAT fibrosis than PWoH, notably in non-obese individuals. Moreover, SAT fibrosis in these PWH was strongly associated with IR, independently of prior legacy ART or ongoing integrase strand inhibitor treatment. This SAT fibrosis was highlighted by a distinct transcriptional pattern marked by upregulation of\n                    <jats:italic>COL14A1<\/jats:italic>\n                    , key immune-related genes (e.g.,\n                    <jats:italic>CCL4<\/jats:italic>\n                    ,\n                    <jats:italic>NLRP3<\/jats:italic>\n                    ), and pathways governing ECM remodeling and immune activation, as well as downregulation of thermogenic, lipid metabolic, and insulin signaling pathways. Plasma endotrophin levels were also elevated in PWH and correlated independently with SAT fibrosis.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>CONCLUSION.<\/jats:bold>\n                    SAT fibrosis was associated with IR independent of obesity in PWH and was mirrored by circulating endotrophin levels, offering a plausible noninvasive biomarker for early intervention. The distinct transcriptional signature of HIV-associated SAT fibrosis highlights candidate mechanisms that may underlie metabolic risk and offer therapeutic avenues in this population.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.195922","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T18:21:16Z","timestamp":1782843676000},"source":"Crossref","is-referenced-by-count":0,"title":["A distinct form of fat fibrosis is linked to insulin resistance in people with HIV"],"prefix":"10.1172","author":[{"given":"Diana L.","family":"Alba","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Zuckerberg San Francisco General Hospital and UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa","family":"Abdellatif","sequence":"additional","affiliation":[{"name":"University of California San Francisco Center for AIDS Research, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moon K.","family":"Choi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Brown Mayfield","sequence":"additional","affiliation":[{"name":"UCSF Diabetes Center, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thuy An T.","family":"Pham","sequence":"additional","affiliation":[{"name":"UCSF Diabetes Center, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David I.","family":"Berrios","sequence":"additional","affiliation":[{"name":"UCSF Diabetes Center, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio E.","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Division of HIV, Infectious Diseases, and Global Medicine, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marin","family":"Ewing","sequence":"additional","affiliation":[{"name":"Division of HIV, Infectious Diseases, and Global Medicine, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony R.","family":"Figueroa","sequence":"additional","affiliation":[{"name":"Division of HIV, Infectious Diseases, and Global Medicine, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy","family":"Gonzalez-Vargas","sequence":"additional","affiliation":[{"name":"UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medic, University of Texas Health Science Center at Houston, Houston, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9309-2335","authenticated-orcid":true,"given":"Zhiqiang","family":"An","sequence":"additional","affiliation":[{"name":"Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medic, University of Texas Health Science Center at Houston, Houston, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawei","family":"Bu","sequence":"additional","affiliation":[{"name":"Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6371-747X","authenticated-orcid":true,"given":"Steven G.","family":"Deeks","sequence":"additional","affiliation":[{"name":"Division of HIV, Infectious Diseases, and Global Medicine, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0680-3392","authenticated-orcid":true,"given":"Philipp E.","family":"Scherer","sequence":"additional","affiliation":[{"name":"Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4571-4870","authenticated-orcid":true,"given":"Peter W.","family":"Hunt","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, Department of Medicine, Zuckerberg San Francisco General Hospital and UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7367-1054","authenticated-orcid":true,"given":"Suneil K.","family":"Koliwad","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,6,30]]},"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/insight.jci.org\/articles\/view\/195922\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T18:21:17Z","timestamp":1782843677000},"score":1,"resource":{"primary":{"URL":"http:\/\/insight.jci.org\/articles\/view\/195922"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,30]]},"references-count":0,"alternative-id":["10.1172\/jci.insight.195922"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.195922","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,30]]}}}