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 clown-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 PPAR gamma 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, clown-regulated upon induction of differentiation and both inhibit beta-catenin dependent Writ signaling at the initiation of adipogenesis. Wnt5b additionally appears to be a potent enhancer ofaclipogenic capacity by stimulation of PPAR gamma and aP2. Down-regulation of Wnt5b Could therefore contribute to decreased adipogenesis observed in T2DM diabetic Subjects. (C) 2009 Elsevier Inc. All rights reserved.