Regulation of adipocyte differentiation and gene expression-crosstalk between TGFβ and wnt signaling pathways

Obesity results in reduced differentiation potential of adipocytes leading to adipose tissue insulin resistance. Elevated proinflammatory cytokines from adipose tissue in obesity, such as TNF alpha have been implicated in the reduced adipocyte differentiation. Other mediators of reduced adipocyte differentiation include TGF beta and wnt proteins. Although some overlap exists in the signaling cascades of the wnt and TGF beta pathways it is unknown if TGF beta or wnt proteins reciprocally induce the expression of each other to maximize their biological effects in adipocytes. Therefore, we investigated the possible involvement of TGF beta signaling in wnt induced gene expression and vice versa in 3T3-L1 adipocyte. Effect of TGF beta and Wnt pathways on differentiation was studied in preadipocytes induced to differentiate in the presence of Wnt3a or TGF beta 1 and their inhibitors (FZ8-CRD and SB431542, respectively). Regulation of intracellular signaling and gene expression was also studied in mature adipocytes. Our results show that both TGF beta 1 and Wnt3a lead to increased accumulation of beta-catenin, phosphorylation of AKT and p44/42 MAPK. However, differences were found in the pattern of gene expression induced by the two proteins suggesting that distinct, but complex, signaling pathways are activated by TGF beta and wnt proteins to independently regulate adipocyte function.