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 H₂ O₂ 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 H₂ O₂ 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.