Age-dependent obesity and mitochondrial dysfunction.

Aging is associated with progressive visceral white adipose tissue (WAT) expansion both in human and mouse. Importantly, WAT enlargement is initiated early in life, suggesting that molecular mechanisms underlying age-dependent obesity are activated at early stages of lifetime. Our recent study found that age-dependent obesity was associated with a specific decline in mitochondrial complex IV activity, which leads to reduced fatty acid oxidation and subsequent adipocyte hypertrophy. At the molecular level, global mitochondrial complex IV inhibition was driven by hypoxia-inducible factor-1α (HIF1α)-mediated repression of some of its key subunits, including cytochrome c oxidase 5b (Cox5b). In this commentary, we compare age-dependent WAT responses with those observed in the high fat diet model of extreme obesity. Furthermore, we discuss the potential scenarios that could initiate age-dependent WAT expansion as well as the mechanisms by which HIF1α could be activated in WAT.