Dataset Information

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

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.

SUBMITTER: Hasan N

PROVIDER: S-EPMC8042177 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Hasan Nazmul N Nagata Naoto N Morishige Jun-Ichi JI Islam Md Tarikul MT Jing Zheng Z Harada Ken-Ichi KI Mieda Michihiro M Ono Masanori M Fujiwara Hiroshi H Daikoku Takiko T Fujiwara Tomoko T Maida Yoshiko Y Ota Tsuguhito T Shimba Shigeki S Kaneko Shuichi S Fujimura Akio A Ando Hitoshi H

Molecular metabolism 20210303

<h4>Objective</h4>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.<h4>Methods</h4>Mice with brown adipocyte-specific knockout of the core clock gene Bmal1 (BA-Bmal1 KO) were generated and analyzed.<h4>Results</h4>The BA-Bmal1 KO mice maintained ...[more]

PMID: 33676029

Similar Datasets

Project description:ObjectiveNon-shivering thermogenesis (NST) mediated by uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) can be activated via the adrenergic system in response to cold or diet, contributing to both thermal and energy homeostasis. Other mechanisms, including metabolism of skeletal muscle, may also be involved in NST. However, relative contribution of these energy dissipating pathways and their adaptability remain a matter of long-standing controversy.MethodsWe used warm-acclimated (30 °C) mice to characterize the effect of an up to 7-day cold acclimation (6 °C; CA) on thermoregulatory thermogenesis, comparing inbred mice with a genetic background conferring resistance (A/J) or susceptibility (C57BL/6 J) to obesity.ResultsBoth warm-acclimated C57BL/6 J and A/J mice exhibited similar cold endurance, assessed as a capability to maintain core body temperature during acute exposure to cold, which improved in response to CA, resulting in comparable cold endurance and similar induction of UCP1 protein in BAT of mice of both genotypes. Despite this, adrenergic NST in BAT was induced only in C57BL/6 J, not in A/J mice subjected to CA. Cold tolerance phenotype of A/J mice subjected to CA was not based on increased shivering, improved insulation, or changes in physical activity. On the contrary, lipidomic, proteomic and gene expression analyses along with palmitoyl carnitine oxidation and cytochrome c oxidase activity revealed induction of lipid oxidation exclusively in skeletal muscle of A/J mice subjected to CA. These changes appear to be related to skeletal muscle NST, mediated by sarcolipin-induced uncoupling of sarco(endo)plasmic reticulum calcium ATPase pump activity and accentuated by changes in mitochondrial respiratory chain supercomplexes assembly.ConclusionsOur results suggest that NST in skeletal muscle could be adaptively augmented in the face of insufficient adrenergic NST in BAT, depending on the genetic background of the mice. It may provide both protection from cold and resistance to obesity, more effectively than BAT.

Dataset Information

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

Objective

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets