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

Mol Metab. 2021 Jul:49:101202. doi: 10.1016/j.molmet.2021.101202. Epub 2021 Mar 3.

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.

Keywords: Brown adipose tissue; Circadian rhythm; Clock genes; Fatty acids; Obesity; Thermogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / genetics*
  • ARNTL Transcription Factors / metabolism*
  • Adipocytes, Brown / metabolism*
  • Adipose Tissue, Brown / metabolism
  • Animals
  • Body Weight
  • Circadian Rhythm
  • Cold Temperature
  • Diet, High-Fat
  • Energy Metabolism
  • Fatty Acids
  • Homeostasis
  • Male
  • Metabolome
  • Mice
  • Mice, Knockout
  • Obesity / metabolism
  • Thermogenesis / genetics*
  • Thermogenesis / physiology*
  • Uncoupling Protein 1 / metabolism

Substances

  • ARNTL Transcription Factors
  • Bmal1 protein, mouse
  • Fatty Acids
  • Ucp1 protein, mouse
  • Uncoupling Protein 1