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

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.

journal_name

J Mol Cell Biol

authors

Meng W,Liang X,Xiao T,Wang J,Wen J,Luo H,Teng J,Fei Y,Zhang Q,Liu B,Hu F,Bai J,Liu M,Zhou Z,Liu F

doi

10.1093/jmcb/mjz056

subject

Has Abstract

pub_date

2019-09-19 00:00:00

pages

781-790

issue

9

eissn

1674-2788

issn

1759-4685

pii

5520427

journal_volume

11

pub_type

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