Growth differentiation factor 11 inhibits adipogenic differentiation by activating TGF‐beta/Smad signalling pathway

OBJECTIVES: Growth differentiation factor 11 (GDF11), an emerging secreted member of the TGF‐beta superfamily, plays essential roles in development, physiology and multiple diseases; however, its role during adipogenic differentiation and the underlying mechanisms remains poorly understood. MATERIALS AND METHODS: Bone marrow‐derived human mesenchymal stem cells (hMSCs) and 3T3‐L1 pre‐adipocytes were induced with adipogenic culture medium supplementing with different concentrations of recombinant GDF11 (rGDF11 0, 10, 50, 100 ng mL(−1)). Oil Red O staining, qRT‐PCR analysis, Western blot analysis and immunofluorescence staining were performed to assay adipogenesis. RESULTS: For both hMSCs and 3T3‐L1 pre‐adipocytes, the presence of rGDF11 leads to a dose‐dependent reduction of intracellular lipid droplet accumulation and suppressed adipogenic‐related gene expression. Mechanically, GDF11 inhibits adipogenesis by activating Smad2/3‐dependent TGF‐beta signalling pathway, and these inhibitory effects could be restored by SB‐431542, a pharmacological TGF‐beta type I receptor inhibitor. CONCLUSIONS: Taken together, our data indicates that GDF11 inhibits adipogenic differentiation in both hMSCs and 3T3‐L1 pre‐adipocytes by activating Smad2/3‐dependent TGF‐beta signalling pathway.