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 Bioljournal_title
Journal of molecular cell biologyauthors
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 Fdoi
10.1093/jmcb/mjz056subject
Has Abstractpub_date
2019-09-19 00:00:00pages
781-790issue
9eissn
1674-2788issn
1759-4685pii
5520427journal_volume
11pub_type
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