Role of Hypoxia Inducible Factors in Obesity Pathogenesis

Abstract

The prevalence of obesity, metabolic syndrome and diabetes has been increasing rapidly worldwide. These are a group of metabolic disorders characterized by a chronic hyperglycaemic condition resulting from defects in insulin secretion, insulin action or both. The control of body weight and blood glucose concentrations depends on the exquisite coordination of the function of several cells, organs and tissues. Underlying mechanisms of obesity and insulin resistance remain uncertain. Adipose tissue is composed of heterogeneous cell types. Immune cells within adipose tissue also likely contribute to systemic metabolic processes. Increased production of local and systemic adipokines and cytokines, polarization of macrophages, T helper subtype changes could contribute to pathologies linking obesity to diabetes, both by decreasing insulin sensitivity, by compromising β-cell function and disturbing adipose tissue metabolism and distribution. Tissue oxygen (O2) levels, hypoxia inducible factor (s) (HIFs) secretion differences regulate the plasticity of macrophages and the polarization of macrophages controls functionally divergent processes in cells. A hypoxic and inflammatory phenotype has been reported in adipose tissue during obesity. Therefore, the present review focuses HIFs-mediated effects of hypoxia in adipocyte inflammation and macrophage polarization associated with obesity pathogenesis.