A distinct form of fat fibrosis is linked to insulin resistance in people with HIV
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Le résumé fourni par la source
BACKGROUNDDespite 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.METHODSWe 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.RESULTSPWH had substantially more SAT fibrosis than PWoH, notably in nonobese individuals. Moreover, SAT fibrosis in these PWH was strongly associated with IR, independent of prior legacy ART or ongoing integrase strand inhibitor treatment. This SAT fibrosis was highlighted by a distinct transcriptional pattern marked by upregulation of COL14A1, key immune-related genes (e.g., CCL4, NLRP3), 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.CONCLUSIONSAT 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.TRIAL REGISTRATIONClinicalTrials.gov NCT03022682.FUNDINGR01DK141041; R01DK112304; R56DK133997; K08DK124679; T32DK007418; P30DK098722; P30AI027763; Robert Wood Johnson Foundation; Harold Amos Medical Faculty Development Program.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- A distinct form of fat fibrosis is linked to insulin resistance in people with HIV
- Date Crossref
- 30/06/2026
- Éditeur
- American Society for Clinical Investigation
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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San Francisco General Hospital Department of Medicine pays non établi dans la noticeÉtablissement de santé
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University of California pays non établi dans la noticeUniversité ou école supérieure
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San Francisco AIDS Foundation pays non établi dans la noticeOrganisation à but non lucratif
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Global Solutions for Infectious Diseases pays non établi dans la noticeOrganisation à but non lucratif
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Brown Foundation pays non établi dans la noticeInstitution
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The University of Texas Southwestern Medical Center Touchstone Diabetes Center pays non établi dans la noticeÉtablissement de santé
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Division of Endocrinology and Metabolism pays non établi dans la noticeInstitution
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UCSF Diabetes Center pays non établi dans la noticeInstitution
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Division of HIV pays non établi dans la noticeInstitution
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University of Texas Health Science Center at Houston Texas Therapeutics Institute pays non établi dans la noticeUniversité ou école supérieure
Department of Medicine — San Francisco General Hospital, University of California et San Francisco AIDS Foundation, avec 7 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.