Department of Internal Medicine III, Leipzig University, Leipzig, Germany.
German Center for Diabetes Research (DZD), Munich, Germany.
Int J Obes (Lond). 2017 Dec;41(12):1815-1823. doi: 10.1038/ijo.2017.172. Epub 2017 Jul 24.
BACKGROUND/OBJECTIVES: Replication initiator 1 (Repin1) gene encodes for a zinc-finger protein and has been implicated in the regulation of adipocyte cell size and glucose transport in vitro. Here, we investigate the consequences of reduced adipose tissue (AT) Repin1 expression in vivo.
SUBJECTS/METHODS: We have inactivated the Repin1 gene in adipose tissue (iARep) at an age of 4 weeks using tamoxifen-inducible gene targeting strategies on the background of C57BL/6NTac mice. Furthermore, we differentiated human primary adipocytes derived from subcutaneous AT in vitro and knocked down REPIN1 using siRNA technique to measure glycerol release.
Conditional Repin1 inactivation results in decreased AT mass, smaller adipocytes in both, subcutaneous and epigonadal AT compared to controls. Compared to controls, iARep mice were more insulin sensitive, had better glucose tolerance and lower LDL-, HDL- and total cholesterol. Significantly lower AT expression of the Repin1 target genes Cd36 and Lcn2 may contribute to the phenotype of iARep mice. Knockdown of REPIN1 in human in vitro differentiated adipocytes revealed an increased glycerol release.
In conclusion, deficiency of Repin1 in AT causes alterations in AT morphology and function, which may underlay lower body weight and improved parameters of insulin sensitivity, glucose and lipid metabolism.
背景/目的：复制起始因子 1（Repin1）基因编码一种锌指蛋白，已被证实参与体外调节脂肪细胞大小和葡萄糖转运。在此，我们研究了体内脂肪组织（AT）Repin1 表达减少的后果。
受试者/方法：我们使用他莫昔芬诱导的基因靶向策略，在 C57BL/6NTac 小鼠背景下，在 4 周龄时使 AT 中的 Repin1 基因失活（iARep）。此外，我们在体外从皮下 AT 分化人类原代脂肪细胞，并使用 siRNA 技术敲低 REPIN1，以测量甘油释放。
条件性 Repin1 失活导致 AT 质量减少，与对照组相比，皮下和附睾 AT 的脂肪细胞更小。与对照组相比，iARep 小鼠的胰岛素敏感性更高，葡萄糖耐量更好，LDL、HDL 和总胆固醇水平更低。Repin1 靶基因 Cd36 和 Lcn2 的 AT 表达显著降低，可能是 iARep 小鼠表型的原因之一。在体外分化的脂肪细胞中敲低 REPIN1 可增加甘油释放。
总之，AT 中 Repin1 的缺乏会导致 AT 形态和功能的改变，这可能是体重降低和改善胰岛素敏感性、葡萄糖和脂质代谢参数的基础。
