Subcutaneous adipose tissue gene transcripts associated with progressive myosteatosis in persons with HIV

Abstract

Objectives: Skeletal muscle fat infiltration (myosteatosis) is a clinical condition distinct from visceral and hepatic lipid accumulation and contributes to metabolic dysregulation, sarcopenia, and frailty in people with HIV (PWH). Altered subcutaneous adipose tissue (SAT) function contributes to visceral fat deposition and hepatic steatosis, but there are few data on SAT gene expression and myosteatosis in PWH on long-term antiretroviral therapy (ART).

Design: A longitudinal analysis of 40 PWH on contemporary ART with sustained viral suppression to assess relationships between SAT gene transcripts and computed tomography (CT) imaging of skeletal muscle density, where lower density indicates higher lipid content, and area. CT imaging also measured other fat depots, including visceral adipose tissue (VAT) volume and liver density.

Methods: SAT gene transcripts were quantified using a NanoString panel of 255 immune and 77 adipocyte-related genes. Linear mixed-effects models assessed baseline SAT gene expression and changes in skeletal muscle over a median of 3.3 years.

Results: Decreasing skeletal muscle density over time correlated with increasing VAT volume and declining liver density. Gene-by-visit interaction revealed 34 SAT genes associated with muscle density change and 15 genes associated with muscle area change. Two key CCR4 binding chemokines, CCL17 and CCL22, were linked to reductions in both muscle density and area.

Conclusions: A subset of SAT gene transcripts is associated with changes in skeletal muscle density and area over time, suggesting interventions to modulate SAT immune activity or improve lipid handling may hold therapeutic potential to slow the progression of myosteatosis and sarcopenia in PWH.

Keywords: HIV; adipose tissue; inflammation; myosteatosis; sarcopenia; skeletal muscle.