Abstract
Adipose tissue maladaptation is central to metabolic alterations in HIV, unhealthy alcohol use and obesity. This involves inflammation, adipokine disruption and dysfunction of adipocytes and the adipocyte extracellular milieu. HIV and simian immunodeficiency virus (SIV) have been shown to increase adipose tissue extracellular matrix (ECM) collagen deposition and impair adipose derived stem cell (ADSC) differentiation. Several aspects of adipocyte biology are regulated by ECM structure and composition. All proteins, regulators and secreted factors contained within the ECM are collectively called the matrisome and largely determines tissue stiffness. In several organs, tissue stiffness has been shown to disrupt normal cellular function and development, but little is known about tissue stiffness in adipose tissue. Using a relevant preclinical model of HIV‐infection, the objective of our study was to investigate the differential effects of chronic binge alcohol (CBA) administration and ovarian hormone loss on alterations in omental (OmAT) and subcutaneous (SAT) adipose tissue phenotype. CBA or isovolumetric water (VEH) was administered through an intragastric catheter for 30 minutes, 5 days a week, with blood alcohol concentrations reaching 50–60 mM. Three months after initiation of CBA administration, macaques were inoculated with SIVMac251 and 2.5 months later initiated on ART. After 1 month of ART, macaques underwent sham surgery or ovariectomy. Our preliminary data indicates that CBA administration increases viral load in adipose tissue. Depot differences were also detected between SAT and OmAT. OmAT has smaller adipocytes compared to SAT with higher anti‐fibrotic gene expression. SAT has higher collagen picrosirius red staining compared to OmAT with higher hormone sensitive lipase lipolytic gene expression. Ovariectomy produced similar effects in both adipose depots by decreasing adipocyte cell size and fibrotic gene expression. Taken together, preliminary data suggest that the maladaptive changes due to alcohol and gonadal hormone loss is potentially depot specific and is mediated by changes of the extracellular matrix. The contributing role of extracellular alterations on adipocyte function and a high fat diet to exacerbate adipose tissue maladaptation are investigated to identify adipose specific mechanisms that can be targeted to improve metabolic dysregulation.Support or Funding InformationNIH/NIAAA P60 AA009803 and 5T32AA007577‐19
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