脂联素抑制脂肪组织MHC Ⅱ表达及对糖脂代谢的影响

Protective effect of adiponectin on glucose and lipid metabolism by suppressing MHC Ⅱ expression

目的:探讨脂联素是否通过影响脂肪组织主要组织相容性复合物Ⅱ类(MHCⅡ)的表达调节糖脂代谢。方法:脂联素基因敲除小鼠(KO)和C57BL/6小鼠(WT)分别给予高脂饲料或普通饲料,24周后,测量小鼠体重、空腹血糖(FBG)、空腹胰岛素(FINS)、稳态胰岛素评价指数(HOMA-IR)、血清甘油三酯(TG)、血清总胆固醇(TC)、血清低密度脂蛋白胆固醇(LDL-C)和血清高密度脂蛋白胆固醇(HDL-C);行肝脏组织病理形态学评价;检测脂肪组织MHCⅡ反式激活因子(CIITA)、小鼠MHCⅡ抗原Eβ(H2-Eb1)、MHCⅡ恒定链(CD74)mRNA及MHCⅡ相关蛋白质表达水平。用siRNA沉默3T3-L1脂肪细胞中MHCⅡ的表达及用过表达载体升高3T3-L1脂肪细胞中的脂联素和(或)MHCⅡ的表达,检测脂联素对MHCⅡ蛋白水平的影响。结果:高脂饲料或普通饲料喂养的KO小鼠体重、FBG、FINS、HOMA-IR、TC、TG、LDL-C、肝脂肪变性、脂肪组织中CIITA、H2-Eb1、CD74 mRNA和MHCⅡ蛋白表达水平均高于WT小鼠。在脂肪细胞中,抑制脂联素能够在一定程度上逆转siRNA干扰所引起的MHCⅡ表达降低,过表达脂联素后脂肪细胞中MHCⅡ的表达降低。结论:脂联素可以通过抑制脂肪组织中MHCⅡ的表达改善糖脂代谢。

AIM ： To investigate whether the protective effect of adiponectin on glucose and lipid metabolism is achieved through down-regulating major histocompatibility complex class Ⅱ （ MHC Ⅱ ） in the adipose tissue. METHODS ： Adiponectin knockout （KO） mice and C57BL/6 （WT） mice were fed with high-fat diet and standard diet for 24 weeks, re- spectively. The body weight, fasting blood glucose （FBG）, fasting insulin （FINS）, homeostasis model assessment of insu- lin resistance （ HOMA-IR）, triglyceride （ TG ） , total cholesterol （ TC ） , low-density lipoprotein cholesterol （ LDL-C ） , high-density lipoprotein cholesterol （HDL-C）, hepatic histology, and class Ⅱtrans-activator （CIITA）, histocompatibility 2 class II antigen E beta （ H2-Ebl ） and cluster of differentiation 74 （CD74） mRNA and MHC II protein levels in adipose tissue were measured at sacrifice, siRNA targeting MHC II and overexpression vector was used in 3T3-L1 cells to explore the effect of adiponectin on the protein level of MHC Ⅱ. RESULTS ： The levels of body weight, FBG, FINS, HOMA-IR, TC, TG, LDL-C, hepatic steatosis, CIITA, H2-Ebl and CD74 mRNA expression, and MHC Ⅱ protein expression in the KO mice were higher than those in the WT mice that fed with high-fat diet or standard diet. In 3T3-L1 cells, inhibition of adiponectin reversed MHC Ⅱ protein level induced by specific siRNA. The expression of MHC Ⅱ in adipocytes decreased after adiponectin was overexpressed. CONCLUSION： Adiponectin improves glucose and lipid metabolism through sup- pressing the expression of MHC Ⅱ in the adipose tissue.