title: Wnt5b stimulates adipogenesis by activating PPARgamma, and inhibiting the beta-catenin dependent Wnt signaling pathway together with Wnt5a.
abstract: Correct Wnt signaling is required for adipogenesis and alterations occur in Type 2 diabetes mellitus (T2DM). Gene expression studies showed that beta-catenin independent Wnt5b was down-regulated in T2DM preadipocytes, while its paralog Wnt5a was unchanged. Our study aimed at defining the expression profile and function of Wnt5a and Wnt5b during adipogenesis by determining their effect on aP2 and PPARgamma expression and assessing the level of beta-catenin translocation in mouse 3T3-L1 preadipocytes. Additionally, we explored the effect on adipogenic capacity by Wnt5b overexpression in combination with stimulation of the beta-catenin dependent or beta-catenin independent Wnt signaling. Expression of Wnt5b was, like Wnt5a, down-regulated upon induction of differentiation and both inhibit beta-catenin dependent Wnt signaling at the initiation of adipogenesis. Wnt5b additionally appears to be a potent enhancer of adipogenic capacity by stimulation of PPARgamma and aP2. Down-regulation of Wnt5b could therefore contribute to decreased adipogenesis observed in T2DM diabetic subjects.
authors: Department of Genetics and Cell Biology, Maastricht University, Maastricht, The Netherlands.
authors: F H J
authors: FH
authors: van Tienen
authors: H
authors: H
authors: Laeremans
authors: C J H
authors: CJ
authors: van der Kallen
authors: H J M
authors: HJ
authors: Smeets
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D050156:Adipogenesis; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D006801:Humans; D051379:Mice; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D000071818:Wnt-5a Protein; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C495267:CTNNB1 protein, mouse; D047495:PPAR gamma; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse; C468567:Wnt5b protein, mouse; D051176:beta Catenin