Institute of Translational Medicine, Nanchang University, Nanchang, China.
School of Life Sciences, Nanchang University, Nanchang, China.
J Cell Mol Med. 2018 Jan;22(1):101-110. doi: 10.1111/jcmm.13297. Epub 2017 Aug 16.
It has been recently reported that CD38 was highly expressed in adipose tissues from obese people and CD38-deficient mice were resistant to high-fat diet (HFD)-induced obesity. However, the role of CD38 in the regulation of adipogenesis and lipogenesis is unknown. In this study, to explore the roles of CD38 in adipogenesis and lipogenesis in vivo and in vitro, obesity models were generated with male CD38 and WT mice fed with HFD. The adipocyte differentiations were induced with MEFs from WT and CD38 mice, 3T3-L1 and C3H10T1/2 cells in vitro. The lipid accumulations and the alternations of CD38 and the genes involved in adipogenesis and lipogenesis were determined with the adipose tissues from the HFD-fed mice or the MEFs, 3T3-L1 and C3H10T1/2 cells during induction of adipocyte differentiation. The results showed that CD38 male mice were significantly resistant to HFD-induced obesity. CD38 expressions in adipocytes were significantly increased in WT mice fed with HFD, and the similar results were obtained from WT MEFs, 3T3-L1 and C3H10T1/2 during induction of adipocyte differentiation. The expressions of PPARγ, AP2 and C/EBPα were markedly attenuated in adipocytes from HFD-fed CD38 mice and CD38 MEFs at late stage of adipocyte differentiation. Moreover, the expressions of SREBP1 and FASN were also significantly decreased in CD38 MEFs. Finally, the CD38 deficiency-mediated activations of Sirt1 signalling were up-regulated or down-regulated by resveratrol and nicotinamide, respectively. These results suggest that CD38 deficiency impairs adipogenesis and lipogenesis through activating Sirt1/PPARγ-FASN signalling pathway during the development of obesity.
最近有报道称，CD38 在肥胖人群的脂肪组织中高度表达，而 CD38 缺陷的小鼠对高脂肪饮食（HFD）诱导的肥胖具有抗性。然而，CD38 在调节脂肪生成和脂肪生成中的作用尚不清楚。在这项研究中，为了探索 CD38 在体内和体外脂肪生成和脂肪生成中的作用，用 HFD 喂养雄性 CD38 和 WT 小鼠来生成肥胖模型。用 WT 和 CD38 小鼠的 MEFs、3T3-L1 和 C3H10T1/2 细胞在体外诱导脂肪细胞分化。用 HFD 喂养小鼠的脂肪组织或 MEFs、3T3-L1 和 C3H10T1/2 细胞在诱导脂肪细胞分化过程中，测定脂肪细胞中的脂质积累和 CD38 及参与脂肪生成和脂肪生成的基因的变化。结果表明，CD38 雄性小鼠对 HFD 诱导的肥胖有明显的抗性。用 HFD 喂养的 WT 小鼠的脂肪细胞中 CD38 的表达明显增加，在诱导脂肪细胞分化过程中，WT MEFs、3T3-L1 和 C3H10T1/2 也得到了类似的结果。在晚期脂肪细胞分化中，HFD 喂养的 CD38 小鼠和 CD38 MEFs 的脂肪细胞中 PPARγ、AP2 和 C/EBPα 的表达明显减弱。此外，CD38 MEFs 中的 SREBP1 和 FASN 的表达也明显降低。最后，用白藜芦醇和烟酰胺分别上调或下调 CD38 缺乏介导的 Sirt1 信号通路的激活。这些结果表明，CD38 缺乏通过在肥胖发展过程中激活 Sirt1/PPARγ-FASN 信号通路来损害脂肪生成和脂肪生成。
