Role of Tissue and Systemic Hypoxia in Obesity and Type 2 Diabetes

Human lifestyle in most modern and developing societies has dramatically changed over past decades. Physical inactivity along with unrestricted access to calorie dense foods has established an “obesogenic” environment and contributed to a serious epidemic of obesity and type 2 diabetes (T2D), associated with increased morbidity and mortality. In 2005 a population-based study conducted by Reichmuth et al. of University of Wisconsin with a cross-sectional and longitudinal analysis identified that among 1387 participants the odds ratio for T2D with an apnea-hypopnea index (AHI) \u3e 15 versus an AHI \u3c 5 was 2.30 (1.28–4.11; p \u3c 0.01) after adjustment for age, sex, and body habitus. Therefore it has been assumed that intermittent hypoxic periods associated with obstructive sleep apnea (OSA) may play a pathogenic role in inducing insulin resistance and T2D. At organ/tissue levels, in 2007–2009 Ye and colleagues first proposed a central role played by adipose tissue hypoxia resulting from adipocyte expansion in promoting chronic inflammation, adiponectin reduction, adipocyte dysfunction, and death in obese individuals. This group of researchers later identified the mediator roles played by hypoxia inducible factor 1α (HIF-1α) and other hypoxia-triggered signaling mechanisms that may promote free fatty acid release and inhibit glucose uptake in adipocytes by inhibition of the insulin-signaling pathway and induction of cell death