Age-induced oxidative stress impairs adipogenesis and thermogenesis in brown fat

It is well-established that the mass and function of human brown adipose tissue (BAT) declines with age. A key factor involved in age-related impairment of BAT is oxidative stress; however, there is a paucity of studies to date that have explored this relationship. Here, we characterized the age-related molecular and functional alterations in BAT in vivo in mice of different ages, and treated human brown adipocytes with H2O2 to dissect the direct effect of oxidative stress in vitro. We further explored the structural and functional changes in BAT in an oxidative stress-induced mouse model of aging. We found that the progressive deterioration of BAT was linked to oxidative stress, and observed that the adipogenesis and thermogenic program were significantly impaired upon H2O2 treatment in vitro. Moreover, antioxidant supplementation (e.g., vitamin E) attenuated oxidative stress and rescued BAT activity decline, suggesting that age-related injury in BAT function can be partly alleviated by antioxidant treatment. Finally, we found that oxidative stress-induced BAT dysfunction is linked to the enhancement of autophagy. These results point to oxidative stress as being an important factor in age-dependent functional impairment of BAT.