Objective: Impaired circadian clocks can cause obesity, but their pathophysiological role 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: Mice with brown adipocyte-specific knockout of the core clock gene Bmal1 (BA-Bmal1 KO) were generated and analyzed.
Results: The BA-Bmal1 KO mice maintained normal core body temperatures 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 the BAT clock for maintaining energy homeostasis and preventing obesity.
Keywords: Brown adipose tissue; Circadian rhythm; Clock genes; Fatty acids; Obesity; Thermogenesis.
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