Single-cell Analysis of Subcutaneous Fat Reveals Pro-fibrotic Cells that Correlate with Visceral Adiposity in HIV

Samuel S Bailin; Curtis L Gabriel; Rama D Gangula; LaToya Hannah; Sangeeta Nair; John Jeffrey Carr; James G Terry; Heidi J Silver; Joshua D Simmons; Mona Mashayekhi; Spyros A Kalams; Simon Mallal; Jonathan A Kropski; Celestine N Wanjalla; John R Koethe

doi:10.1210/clinem/dgae369

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Single-cell Analysis of Subcutaneous Fat Reveals Pro-fibrotic Cells that Correlate with Visceral Adiposity in HIV

Journal article

Open access

Single-cell Analysis of Subcutaneous Fat Reveals Pro-fibrotic Cells that Correlate with Visceral Adiposity in HIV

Samuel S Bailin, Curtis L Gabriel, Rama D Gangula, LaToya Hannah, Sangeeta Nair, John Jeffrey Carr, James G Terry, Heidi J Silver, Joshua D Simmons, Mona Mashayekhi, …

The journal of clinical endocrinology and metabolism, Vol.110(1), pp.238-253

2024

DOI: https://doi.org/10.1210/clinem/dgae369

PMID: 38820087

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Abstract

single-cell RNA sequencing

HIV

inflammation

insulin resistance

visceral adipose tissue

Context Cardiometabolic diseases are common in persons with HIV (PWH) on antiretroviral therapy (ART), which has been attributed to preferential lipid storage in visceral adipose tissue (VAT) compared with subcutaneous adipose tissue (SAT). However, the relationship of SAT-specific cellular and molecular programs with VAT volume is poorly understood in PWH. Objective We characterized SAT cell-type specific composition and transcriptional programs that are associated with greater VAT volume in PWH on contemporary ART. Methods We enrolled PWH on long-term ART with a spectrum of metabolic health. Ninety-two participants underwent SAT biopsy for bulk RNA sequencing and 43 had single-cell RNA sequencing. Computed tomography quantified VAT volume and insulin resistance was calculated using the Homeostasis Model Assessment 2 Insulin Resistance (HOMA2-IR). Results VAT volume was associated with HOMA2-IR (P < .001). Higher proportions of SAT intermediate macrophages (IMs), myofibroblasts, and MYOC+ fibroblasts were associated with greater VAT volume using partial Spearman's correlation adjusting for age, sex, and body mass index (r = 0.34-0.49, P < .05 for all). Whole SAT transcriptomics showed PWH with greater VAT volume have increased expression of extracellular matrix (ECM)– and inflammation-associated genes, and reduced expression of lipolysis- and fatty acid metabolism–associated genes. Conclusion In PWH, greater VAT volume is associated with a higher proportion of SAT IMs and fibroblasts, and a SAT ECM and inflammatory transcriptome, which is similar to findings in HIV-negative persons with obesity. These data identify SAT cell-type specific changes associated with VAT volume in PWH that could underlie the high rates of cardiometabolic diseases in PWH, though additional longitudinal studies are needed to define directionality and mechanisms.

Details

Title: Single-cell Analysis of Subcutaneous Fat Reveals Pro-fibrotic Cells that Correlate with Visceral Adiposity in HIV
Authors/Creators: Samuel S Bailin - Vanderbilt University Medical Center
Curtis L Gabriel - Vanderbilt University Medical Center
Rama D Gangula - Vanderbilt University Medical Center
LaToya Hannah - Vanderbilt University Medical Center
Sangeeta Nair - Vanderbilt University Medical Center
John Jeffrey Carr - Vanderbilt University Medical Center
James G Terry - Vanderbilt University Medical Center
Heidi J Silver - Vanderbilt University Medical Center
Joshua D Simmons - Tennessee Center for AIDS Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA
Mona Mashayekhi - Vanderbilt University Medical Center
Spyros A Kalams - Vanderbilt University Medical Center
Simon Mallal - Vanderbilt Technologies for Advanced Genomics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
Jonathan A Kropski - Vanderbilt University Medical Center
Celestine N Wanjalla - Vanderbilt University Medical Center
John R Koethe - Vanderbilt University Medical Center
Publication Details: The journal of clinical endocrinology and metabolism, Vol.110(1), pp.238-253
Publisher: Oxford University Press on behalf of the Endocrine Society.
Identifiers: 991005680461307891
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.66 HIV; 1.66.1372 HIV Comorbidities
Web Of Science research areas: Endocrinology & Metabolism
ESI research areas: Clinical Medicine