title: Activation of PPARγ2 by PPARγ1 through a functional PPRE in transdifferentiation of myoblasts to adipocytes induced by EPA.
abstract: PPARγ 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 PPARγ expression and Wnt signaling. During the early stage of transdifferentiation, EPA activates PPARδ and PPARγ1, which in turn targets β-catenin to degradation and down-regulates Wnt/β-catenin signaling, such that the myogenic fate of myoblasts could be switched to adipogenesis. In addition, EPA up-regulates the expression of PPARγ1 by activating RXRα, then PPARγ1 binds to the functional peroxisome proliferator responsive element (PPRE) in the promoter of adipocyte-specific PPARγ2 to continuously activate the expression of PPARγ2 throughout the transdifferentiation process. Our data indicated that EPA acts as a dual-function stimulator of adipogenesis that both inhibits Wnt signaling and induces PPARγ2 expression to facilitate the transdifferentiation program, and the transcriptional activation of PPARγ2 by PPARγ1 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.
authors.affiliation: a Department of Animal Nutrition and Feed Science; College of Animal Science and Technology; Huazhong Agricultural University ; Wuhan , China.
authors.forename: Hefeng
authors.initials: H
authors.lastname: Luo
authors.forename: Yuanfei
authors.initials: Y
authors.lastname: Zhou
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Hu
authors.forename: Xuewu
authors.initials: X
authors.lastname: Peng
authors.forename: Hongkui
authors.initials: H
authors.lastname: Wei
authors.forename: Jian
authors.initials: J
authors.lastname: Peng
authors.forename: Siwen
authors.initials: S
authors.lastname: Jiang
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D054338:Cell Transdifferentiation; D015118:Eicosapentaenoic Acid / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D032446:Myoblasts / Q000378:metabolism*; D047494:PPAR delta / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020218:Response Elements; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction; D015533:Transcriptional Activation; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D047494:PPAR delta; D047495:PPAR gamma; D051153:Wnt Proteins; D051176:beta Catenin; D015118:Eicosapentaenoic Acid
keywords: BSA, bovine serum albumin; C/EBP, CCAAT/enhancer-binding protein; DHA, docosahexaenoic acid; DMEM, Dulbecco's modified Eagle's medium; EPA, eicosapentaenoic acid; IMF, intramuscular fat; PPAR, peroxisome proliferator-activated receptor; PPARγ1; PPARγ2; PPARδ; PPRE, peroxisome proliferator responsive element; PUFA, polyunsaturated fatty acids; RXR, retinoid X receptor.; Wnt/β-catenin signaling; eicosapentaenoic acid; transdifferentiation