Brown adipocyte-specific knockout of Bmal1 causes mild but significant impairment of thermogenesis in mice.

Abstract Objective The impairment of circadian clocks is a cause of obesity, but the pathophysiological role of the circadian clock in brown adipose tissue (BAT), a major tissue regulating energy metabolism, remains unclear. To address this issue, we investigated the effects of complete disruption of the BAT clock on thermogenesis and energy expenditure. Methods The mice with brown adipocyte-specific knockout of the core clock gene Bmal1 (BA-Bmal1 KO) were generated and analyzed. Results BA-Bmal1 KO mice maintained normal core body temperature by increasing shivering and locomotor activity, despite the elevated expression of thermogenic uncoupling protein 1 in BAT. BA-Bmal1 KO disrupted 24 h rhythmicity of fatty acid utilization in BAT, and mildly reduced both BAT thermogenesis and whole-body energy expenditure. The impact of BA-Bmal1 KO on the development of obesity became obvious when the mice were fed a high-fat diet. Conclusions These results reveal the importance of BAT clock for the maintenance of energy homeostasis and the prevention of obesity.