Fundamental roles for hypoxia signalling in adipose tissue metabolism and inflammation in obesity

Over a decade ago the notion that adipose tissue could become hypoxic during adipose expansion with obesity was proposed. A series of elegant studies in mouse models of obesity have demonstrated that severe adiposity could lead to low oxygen levels within adipose tissue, triggering induction of the hypoxia inducible factor (HIF) signalling cascade, and consequently an upregulation of pro-inflammatory responses that lead to insulin resistance. However, genetic models targeting different components of the HIF pathway have produced conflicting results and revealing that distinct HIF isoforms play tissue-specific roles in metabolic function. This review discusses the consequences and mechanisms of altered oxygenation on adipocyte function and the potential for therapeutic targeting of HIF signalling in obesity and its metabolic complications.