Rheb promotes brown fat thermogenesis by Notch-dependent activation of the PKA signaling pathway

Wen Meng, Xiuci Liang, Ting Xiao, Jing Wang, Jie Wen, Hairong Luo, Jianhui Teng, Yanquan Fei, Qinghai Zhang, Bilian Liu, Fang Hu, Juli Bai, Meilian Liu, Zhiguang Zhou, Feng Liu

Research output: Contribution to journalArticle

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Abstract

Increasing brown and beige fat thermogenesis have an anti-obesity effect and thus great metabolic benefits. However, the molecular mechanisms regulating brown and beige fat thermogenesis remain to be further elucidated. We recently found that fat-specific knockout of Rheb promoted beige fat thermogenesis. In the current study, we show that Rheb has distinct effects on thermogenic gene expression in brown and beige fat. Fat-specific knockout of Rheb decreased protein kinase A (PKA) activity and thermogenic gene expression in brown adipose tissue of high-fat diet-fed mice. On the other hand, overexpression of Rheb activated PKA and increased uncoupling protein 1 expression in brown adipocytes. Mechanistically, Rheb overexpression in brown adipocytes increased Notch expression, leading to disassociation of the regulatory subunit from the catalytic subunit of PKA and subsequent PKA activation. Our study demonstrates that Rheb, by selectively modulating thermogenic gene expression in brown and beige adipose tissues, plays an important role in regulating energy homeostasis.

Original languageEnglish (US)
Pages (from-to)781-790
Number of pages10
JournalJournal of molecular cell biology
Volume11
Issue number9
DOIs
Publication statusPublished - Sep 19 2019

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Keywords

  • adipose tissue
  • beiging
  • energy homeostasis
  • obesity
  • thermogenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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