The Primacy of Adipose Tissue Gene Expression and Plasma Lipidome in Cardiometabolic Disease in Persons With HIV

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background Persons with HIV (PWH) on contemporary antiretroviral therapy (ART) are at elevated risk for developing age-related cardiometabolic diseases. We hypothesized that integrative analysis of cross-tissue, multimodal data from PWH could provide insight into molecular programming that defines cardiometabolic phenotypes in this high-risk group. Methods We enrolled 93 PWH without diabetes who were virologically suppressed on contemporary ART and obtained measures of insulin resistance, glucose intolerance, and adiposity. We performed circulating lipidomics, proteomics, and metabolomics, as well as subcutaneous adipose tissue (SAT) bulk transcriptomics, and used multiomics factor analysis (MOFA) to perform integrative analyses of these datasets. Results The median age was 43 years, median body mass index 30.8 kg/m2, 81% were male, and 56% were self-identified non-Hispanic White. We identified a specific MOFA factor associated with visceral adipose tissue volume (ρ = -0.43), homeostasis model assessment 2 insulin resistance score (ρ = -0.52), liver density (ρ = 0.43), and other cardiometabolic risk factors, which explained more variance in the SAT transcriptome and circulating lipidome compared with the circulating proteome and metabolome. Gene set enrichment analysis of this factor showed extracellular matrix and inflammatory pathways that primarily mapped to SAT myeloid cell

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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