CD38 deficiency suppresses adipogenesis and lipogenesis in adipose tissues through activating Sirt1/PPARγ signaling pathway

Abstract It has been recently reported that CD 38 was highly expressed in adipose tissues from obese people and CD 38‐deficient mice were resistant to high‐fat diet ( HFD )‐induced obesity. However, the role of CD 38 in the regulation of adipogenesis and lipogenesis is unknown. In this study, to explore the roles of CD 38 in adipogenesis and lipogenesis in vivo and in vitro , obesity models were generated with male CD 38 −/− and WT mice fed with HFD . The adipocyte differentiations were induced with MEF s from WT and CD 38 −/− mice, 3T3‐L1 and C3H10T1/2 cells in vitro . The lipid accumulations and the alternations of CD 38 and the genes involved in adipogenesis and lipogenesis were determined with the adipose tissues from the HFD ‐fed mice or the MEF s, 3T3‐L1 and C3H10T1/2 cells during induction of adipocyte differentiation. The results showed that CD 38 −/− male mice were significantly resistant to HFD ‐induced obesity. CD 38 expressions in adipocytes were significantly increased in WT mice fed with HFD , and the similar results were obtained from WT MEF s, 3T3‐L1 and C3H10T1/2 during induction of adipocyte differentiation. The expressions of PPAR γ, AP 2 and C/ EBP α were markedly attenuated in adipocytes from HFD ‐fed CD 38 −/− mice and CD 38 −/− MEF s at late stage of adipocyte differentiation. Moreover, the expressions of SREBP 1 and FASN were also significantly decreased in CD 38 −/− MEF s. Finally, the CD 38 deficiency‐mediated activations of Sirt1 signalling were up‐regulated or down‐regulated by resveratrol and nicotinamide, respectively. These results suggest that CD 38 deficiency impairs adipogenesis and lipogenesis through activating Sirt1/ PPAR γ‐ FASN signalling pathway during the development of obesity.