·糖尿病基础研究·

　　王葱 杨刚毅 李伶 孙滨 李珂

　　基金项目：国家自然科学基金项目(30771037，81070640，30871199和30971388)

　　作者单位：400010重庆医科大学附属第二医院内分泌科(王葱、杨刚毅、 李钶);重庆医科大学检验系临床生化教研室和教育部实验诊断重点实验室(李伶、孙滨)

　　通讯作者：杨刚毅，E-mail: gangyiyang@yahoo.com.cn

　　【摘要】目的探讨高脂诱导IR对apoE-/-小鼠TG代谢相关基因的影响。方法健康雄性apoE-/-小鼠，随机分为普食组(NF组，n=10)和高脂喂养组(HF组，n=10)共喂养16周。采用实时荧光定量PCR测定组织TG代谢相关基因：脂肪细胞甘油三酯酶(ATGL)，激素敏感性脂肪酶(HSL)，过氧化物酶体增殖物激活受体γ(PPARγ) mRNA表达，同时测定了脂肪组织ATGL蛋白水平。结果高脂喂养组小鼠空腹血糖、血浆胰岛素、胆固醇、游离脂肪酸(FFA)和TG明显升高(P均<0.01); 肝组织和脂肪组织ATGL和PPARγ mRNA的表达水平明显降低(P<0.01和P<0.05);而HSL mRNA表达没有明显变化。此外，高脂喂养组小鼠脂肪组织ATGL蛋白水平也明显低于普食组(P<0.01)。结论高脂喂养apoE-/-小鼠产生了明显的IR，可能与TG代谢相关基因及其蛋白水平的表达下调有关。

　　【关键词】ApoE-/-小鼠;胰岛素抵抗;甘油三酯代谢; 基因表达

　　doi:10.3969/j.issn.1006-6187.2012.03.018

　　The effects of high fat-induced insulin resistance on gene expression involving triglyceride metabolism in ApoE-/- miceWANG Cong , YANG Gang-yi , LI Ling, et al. Department of Endocrinology, the Second Affiliated Hospital, and Department of Clinical Biochemistry and the Key Laboratory of Laboratory Medical Diagnostics in the Ministry of Education, Chongqing Medical University, Chongqing 400016, China

　　Corresponding author: YANG Gang-yi , Email: gangyiyang@yahoo.com.cn

　　【Abstract】ObjectiveTo investigate the effects of high fat- induced insulin resistance ( IR ) on gene expression involving triglyceride (TG) metabolism in apoE-/- mice.MethodHealthy male apoE-/- mice were randomly divided into normal-chow group (NF, n=10) and high-fat fed group (HF, n=10) and fed for 16 weeks. The mRNA expression of adipose triglyceride lipase (ATGL) , hormone sensitive lipase (HSL) and peroxisome proliferator-activated-receptor-γ (PPARγ) were measured by quantitative real-time PCR. ATGL protein level in adipose tissues was determined by Western blot.ResultsFasting blood glucose (FBG), plasma insulin , free fatty acids(FFA), TG, total cholesterol (TC) , high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were significantly elevated in HF group compared with NF group (all P<0.01). The mRNA levels of ATGL and PPARγ in hepatic and adipose tissues were significantly lower in HF group than in NF group (P<0.01 and P<0.05), and the ATGL protein levels in adipose tissues were also lower in HF group than in NF group (P<0.01).ConclusionThe high-fat-diet-fed mice with apoE-/- develop insulin resistance, which may induce the mRNA and protein down-regulate expression of genes involving TG metabolism.

　　【Key words】ApoE-/- mice; Insulin resistance; TG metabolism; Gene expression