A Distinct Form of Fat Fibrosis Is Linked to Insulin Resistance in People With HIV

Authors

• Diana L Alba
• Alaa Abdellatif
• Moon Kyung Choi
• Stephen M Brown Mayfield
• Thuy An T Pham
• David I Berrios
• Antonio E Rodriguez
• Marin Ewing
• Tony R Figueroa
• Judy Gonzalez-Vargas
• Ningyan Zhang
• Zhiqiang An
• Dawei Bu
• Steven G Deeks
• Philipp E Scherer
• Peter W Hunt
• Suneil K Koliwad

Language

English

Publication Date

8-10-2026

Journal

JCI Insight

DOI

10.1172/jci.insight.195922

PMID

42378059

PMCID

PMC13463614

PubMedCentral® Posted Date

6-30-2026

PubMedCentral® Full Text Version

Post-print

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

PWH 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.

CONCLUSION

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.

Keywords

Humans, Insulin Resistance, HIV Infections, Female, Male, Fibrosis, Middle Aged, Adult, Subcutaneous Fat, Obesity, Diabetes Mellitus, Type 2, Peptide Fragments, Collagen Type VI

Comments

TRIAL REGISTRATION

ClinicalTrials.gov NCT03022682.

Published Open-Access

yes

Recommended Citation

Alba, Diana L; Abdellatif, Alaa; Choi, Moon Kyung; et al., "A Distinct Form of Fat Fibrosis Is Linked to Insulin Resistance in People With HIV" (2026). The Brown Foundation: Institute of Molecular Medicine. 89.
https://digitalcommons.library.tmc.edu/molecular_med/89