Response to a Long-term High-Fat Diet in the Signature of Genes Involved in Lipid Metabolism in ApoE−/− Mice
Response to a Long-term High-Fat Diet in the Signature of Genes Involved in Lipid Metabolism in ApoE−/− Mice
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DOI：
10.1097/maj.0b013e3182688026
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发表时间：
2013-09
期刊：
影响因子：
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通讯作者：
Mengliu Yang;Shengbing Li;Hua Liu;Gangyi Yang;Lingou Li
中科院分区：
文献类型：
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作者：
Mengliu Yang;Shengbing Li;Hua Liu;Gangyi Yang;Lingou Li
翻译后摘要：高脂饮食（HFD）诱导的脂质代谢紊乱是饮食诱导的胰岛素抵抗（IR）的一个重要特征，然而，HFD的组织特异性影响的机制，参与脂质代谢的基因的签名尚未得到充分的研究。使用高胰岛素-正葡萄糖钳夹技术监测了喂食普通饲料和喂食HFD的ApoE−/−小鼠的葡萄糖稳态和胰岛素敏感性。通过定量实时聚合酶链反应和蛋白质印迹分析，在肝脏和脂肪组织中测量参与脂质代谢的基因的特征。长期HFD（16周）导致葡萄糖和脂质代谢明显异常，并诱导ApoE−/−小鼠IR。长期HFD还显著上调肝脏和/或脂肪组织中胰岛素诱导基因-2、固醇调节元件结合蛋白裂解激活蛋白和固醇调节元件结合蛋白-1的信使RNA（mRNA）表达，同时肝脏中胰岛素诱导基因-2蛋白升高。然而，HFD显着下调胆固醇调节元件结合蛋白-2，3-羟基-3-甲基戊二酰辅酶A还原酶和低密度脂蛋白受体在肝脏中的mRNA表达。有趣的是，长期HFD显着降低脂肪甘油三酯脂肪酶和过氧化物酶体增殖物激活受体- mRNA，和脂肪甘油三酯脂肪酶在肝脏和/或脂肪组织中的蛋白质含量。这些发现提供了一个框架，以了解机制，长期HFD调节参与脂质代谢的基因签名在饮食诱导的IR的发病机制。
Abstract:High-fat diet (HFD)-induced lipid metabolism disorders are a critical feature of diet-induced insulin resistance (IR); however, the mechanisms underlying the tissue-specific effects of HFDs on the signature of genes involved in lipid metabolism have not been fully investigated. Glucose homeostasis and insulin sensitivity were monitored in chow-fed and HFD-fed ApoE−/− mice using the hyperinsulinemic-euglycemic clamp technique. The signatures of genes involved in lipid metabolism were measured in the liver and adipose tissues by quantitative real-time polymerase chain reaction and Western blot analysis. Long-term HFD (for 16 weeks) resulted in marked abnormalities in glucose and lipid metabolism and induced IR in ApoE−/− mice. Long-term HFD also markedly upregulated the messenger RNA (mRNA) expression of insulin-induced gene-2, sterol regulatory element-binding protein cleavage-activating protein and sterol regulatory element-binding protein-1 in the liver and/or adipose tissues, in parallel with an elevated insulin-induced gene-2 protein in the liver. However, HFD markedly downregulated the mRNA expression of sterol regulatory element-binding protein-2, 3-hydroxy-3-methylglutaryl coenzyme A reductase and low-density lipoprotein receptor in the liver. Interestingly, long-term HFD markedly decreased adipose triglyceride lipase and peroxisome proliferator-activated receptor- mRNA, and adipose triglyceride lipase protein contents in the liver and/or adipose tissues. These findings provide a framework to understand the mechanisms by which long-term HFD regulates the gene signatures involved in lipid metabolism in the pathogenesis of diet-induced IR.