Conversion of Non-adipogenic Fibroblasts into Adipocytes by a Defined Hormone Mixture

We report here for the first time that NIH-3T3 fibroblasts, which are generally considered to be non-adipogenic, can be converted into mature adipocytes by treatment with a defined hormone mixture comprising epidermal growth factor (EGF), hepatocyte growth factor (HGF), dexamethasone (Dex), and insulin. Furthermore, NIH-3T3 cells transplanted into obese immunodeficient NOD-SCID mice formed adipocytes in vivo. Interestingly, the mixture elicited conversion of NIH-3T3 cells directly into adipocytes without a preceding pre-adipocyte stage. Functional analysis revealed that each component of the mixture was necessary for the induction of adipogenesis, including Dex which inhibited the cell proliferation stimulated by EGF. Upon profiling the signaling pathways employed by EGF and HGF, we found Stat5 signaling to be activated, predominantly at the levels of both transcription and post-translational modification. Inhibition of the Stat5 pathway, either by genetic knockdown or a specific pharmacological agent, blocked adipogenesis in NIH-3T3 cells. Taken together, these data not only establish a newly-recognized grouping of factors that can induce trans-differentiation of non-adipogenic fibroblasts into adipocytes, but also give us more understanding of obesity.

Source: BJ Cell - March 2, 2015 Category: Biochemistry Authors: T Nie, X Hui, X Gao, B Nie, L Mao, X Tang, R Yuan, K Li, P Li, A Xu, P Liu, S Ding, W Han, G Cooper, D Wu Tags: BJ Cell Source Type: research