PGE₂ -EP3 axis promotes brown adipose tissue formation through stabilization of WTAP RNA methyltransferase.

ABSTRACT: Brown adipose tissue (BAT) functions as a thermogenic organ and is negatively associated with cardiometabolic diseases. N⁶ -methyladenosine (m⁶ A) modulation regulates the fate of stem cells. Here, we show that the prostaglandin E₂ (PGE₂ )-E-prostanoid receptor 3 (EP3) axis was activated during mouse interscapular BAT development. Disruption of EP3 impaired the browning process during adipocyte differentiation from pre-adipocytes. Brown adipocyte-specific depletion of EP3 compromised interscapular BAT formation and aggravated high-fat diet-induced obesity and insulin resistance in vivo. Mechanistically, activation of EP3 stabilized the Zfp410 mRNA via WTAP-mediated m⁶ A modification, while knockdown of Zfp410 abolished the EP3-induced

SUBMITTER: Tao X 

PROVIDER: S-EPMC9379545 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature