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

Abstract

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.

Loss of Uncoupling Protein 3 Attenuates Western Diet–Induced Obesity, Systemic Inflammation, and Insulin Resistance in Rats

“…Chouchani et al (34) demonstrated a critical role for increased mitochondrial ROS generation in activation of UCP1 and subsequent thermogenic energy expenditure of BAT with cold exposure. However, increased oxidative stress has also been associated with the impairment of adipogenesis and thermogenesis in BAT during aging (35). Like white adipocytes, brown fat cells are prone to becoming dysfunctional when challenged with excess nutrients and ROS (36).…”

Energy Metabolism and Aging

“…In humans, the largest depot of BAT can be found in the supraclavicular region [56,58,59]. Fifty grams of BAT mass accounts for 3% to 5% of a human subject's basal metabolic rate [60]. In mice, BAT differs anatomically from human BAT because it is concentrated in specific depots (e.g., the interscapular depot), whereas in humans, brown adipocytes tend to be dispersed within white adipose depots.…”

“…This caused a decline in BAT cells. Importantly, it was also shown that antioxidant treatment reduced the effects of oxidative stress and reversed BAT activity decline [60]. Mitochondrial dysfunction can develop during aging, causing a decrease in fuel oxidation overall and a buildup of reactive oxidative species [60].…”

“…Importantly, it was also shown that antioxidant treatment reduced the effects of oxidative stress and reversed BAT activity decline [60]. Mitochondrial dysfunction can develop during aging, causing a decrease in fuel oxidation overall and a buildup of reactive oxidative species [60]. These reactive species are likely responsible for an increase in metabolic dysfunction rates with age, but antioxidant supplements could reduce these effects and reverse BAT deterioration.…”

Regulatory roles of circRNAs in adipogenesis and lipid metabolism: emerging insights into lipid‐related diseases

“…lipid metabolism, respectively. WAT is essential for energy storage and regulation of energy homeostasis, while BAT is characterized by thermogenesis and energy expenditure [6,7]. Interestingly, in the presence of certain stimuli, WAT can be transformed into BAT, this process is called browning [8].…”