Obesity and Fat Metabolism in HIV-infected Individuals: Immunopathogenic Mechanisms and Clinical Implications.

Abstract

Metabolic complications relating to complex effects of viral and immune mediated mechanisms are now a focus of clinical care among persons living with HIV (PWH) and obesity is emerging as a critical problem. To address knowledge gaps, the NIH sponsored a symposium in May 2018 entitled Obesity and Fat Metabolism in HIV-infected Individuals. Mechanisms relating to adipose dysfunction and fibrosis, immune function, inflammation, and gastrointestinal integrity were highlighted as contributors to obesity among PWH. Fibrotic subcutaneous adipose tissue is metabolically dysfunctional and loses its capacity to expand leading to fat redistribution, including visceral obesity and ectopic fat accumulation, promoting insulin resistance. Viral proteins, including viral-protein-r (vpr) and negative-regulatory-factor (nef) have effects on adipogenic pathways and cellular metabolism in resident macrophages and T-cells. HIV also affects immune cell trafficking into the adipose compartments, with effects on adipogenesis, lipolysis, and ectopic fat accumulation. Key cellular metabolic functions are likely to be affected in PWH by gut derived cytokines and altered microbiota. There are limited strategies to reduce obesity specifically in PWH, enhancing our understanding of critical pathogenic mechanisms will enable the development of novel therapeutics which may normalize adipose tissue function and distribution, reduce inflammation, and improve insulin sensitivity in PWH.