Brown adipocyte-specific knockout of Bmal1 causes mild but significant thermogenesis impairment in mice
Nazmul Hasan, Naoto Nagata, Jun‐ichi Morishige, Md Tarikul Islam, Zheng Jing, Kenichi Harada, Michihiro Mieda, Masanori Ono, Hiroshi Fujiwara, Takiko Daikoku, Tomoko Fujiwara, Yoshiko Maida, Tsuguhito Ota, Shigeki Shimba, Shuichi Kaneko, Akio Fujimura, Hitoshi Ando
Abstract
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.