Activation of PPAR?2 by PPAR?1 through a functional PPRE in transdifferentiation of myoblasts to adipocytes induced by EPA.

ABSTRACT: PPAR? and Wnt signaling are central positive and negative regulators of adipogenesis, respectively. Here we identified that, eicosapentaenoic acid (EPA) could effectively induce the transdifferentiation of myoblasts into adipocytes through modulation of both PPAR? expression and Wnt signaling. During the early stage of transdifferentiation, EPA activates PPAR? and PPAR?1, which in turn targets ?-catenin to degradation and down-regulates Wnt/?-catenin signaling, such that the myogenic fate of myoblasts could be switched to adipogenesis. In addition, EPA up-regulates the expression of PPAR?1 by activating RXR?, then PPAR?1 binds to the functional peroxisome proliferator responsive element (PPRE) in the promoter of adipocyte-specific PPAR?2 to continuously activate the expression of PPAR?2 throughout the transdifferentiation process. Our data indicated that EPA acts as a dual-function stimulator of adipogenesis that both inhibits Wnt signaling and induces PPAR?2 expression to facilitate the transdifferentiation program, and the transcriptional activation of PPAR?2 by PPAR?1 is not only the key factor for the transdifferentiation of myoblasts to adipocytes, but also the crucial evidence for successful transdifferentiation. The present findings provided insight for the first time as to how EPA induces the transdifferentiation of myoblasts to adipocytes, but also provide new clues for strategies to prevent and treat some metabolic diseases.

SUBMITTER: Luo H 

PROVIDER: S-EPMC4614827 | biostudies-other | 2015

REPOSITORIES: biostudies-other