Stromal Vascular Cell-Mediated Inflammatory and Remodeling Pathways in Alcohol-Induced Visceral Adipose Tissue Dysfunction: A Pilot Study

Abstract

Chronic alcohol use induces adipocyte lipolysis and production of inflammatory mediators from adipose tissue (AT). Stromal vascular cells (SVCs) are a heterogeneous group of AT cells and contribute to AT inflammation and remodeling in metabolic syndrome. However, the role of SVCs in promoting AT dysfunction upon alcohol exposure remains unclear. Male rats were fed a Lieber–DeCarli diet containing 6.7% (v/v) ethanol (ET) or an isocaloric control diet (CON) for six weeks. Primary rat SVCs were isolated from visceral AT (VAT) of CON and ET rats. RNA sequencing analysis was performed to determine the overall changes in the gene-expression profile. Real-time PCR, Western blotting, and histological analyses were performed to validate the transcriptomics results. Chronic alcohol feeding decreased the adipocyte size and increased the formation of crown-like structures in the rat VAT. RNA-seq analysis revealed that signaling pathways related to cellular response to interleukin 1 (IL1) and collagen-containing extracellular matrix were significantly altered upon ethanol exposure in SVCs. Along these lines, ethanol exposure increased the protein levels of purinergic receptor P2Y2 (P2RY2) and IL1β in the SVCs of rat VAT. Furthermore, ethanol increased collagen deposition in both interstitial and perivascular regions, which was associated with an increase in the level of phosphorylated SMAD2/3 and collagen type VIII alpha 1 chain expression. These findings suggest that chronic ethanol exposure is associated with inflammatory and remodeling-related alterations in VAT and the total VAT-derived SVC fraction. This exploratory pilot study identifies P2RY2-associated inflammatory markers and TGFβ-related remodeling markers as candidates for future mechanistic investigation.