Inhibition of ADRP prevents diet-induced insulin resistance
Inhibition of ADRP prevents diet-induced insulin resistance
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DOI：
10.1152/ajpgi.90204.2008
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发表时间：
2008-09-01
影响因子：
4.5
通讯作者：
Ahima, Rexford S.
中科院分区：
文献类型：
--
作者：
Varela, Gladys M.;Antwi, Daniel A.;Ahima, Rexford S.
高脂肪含量的饮食会诱发脂肪变性、胰岛素抵抗和2型糖尿病。脂滴蛋白脂肪分化相关蛋白（ADRP）介导肝脂肪变性，但这是否影响胰岛素在肝脏或周围器官的饮食诱导的肥胖是不确定的。我们给C57 BL/6 J小鼠喂高脂饲料，同时用ADRP反义寡核苷酸（阿索）治疗4周。采用钳夹和示踪技术评价葡萄糖稳态。ADRP阿索降低了肝脏中甘油三酯和二酰甘油的水平，但脂肪酸、长链脂肪酰辅酶A、神经酰胺和胆固醇无变化。ADRP阿索治疗后，肝脏中的胰岛素作用增强，而肌肉和脂肪组织不受影响。ADRP阿索可增加胰岛素受体底物（IRS）1、IRS 2和Akt的磷酸化，降低促胰岛素生成酶和PKC β，与其胰岛素增敏作用一致。这些结果表明ADRP在饮食诱导的胰岛素抵抗的发病机制中起重要作用。
Diets with high fat content induce steatosis, insulin resistance, and type 2 diabetes. The lipid droplet protein adipose differentiation-related protein (ADRP) mediates hepatic steatosis, but whether this affects insulin action in the liver or peripheral organs in diet-induced obesity is uncertain. We fed C57BL/6J mice a high-fat diet and simultaneously treated them with an antisense oligonucleotide (ASO) against ADRP for 4 wk. Glucose homeostasis was assessed with clamp and tracer techniques. ADRP ASO decreased the levels of triglycerides and diacylglycerol in the liver, but fatty acids, long-chain fatty acyl CoAs, ceramides, and cholesterol were unchanged. Insulin action in the liver was enhanced after ADRP ASO treatment, whereas muscle and adipose tissue were not affected. ADRP ASO increased the phosphorylation of insulin receptor substrate (IRS)1, IRS2, and Akt, and decreased gluconeogenic enzymes and PKC epsilon, consistent with its insulin-sensitizing action. These results demonstrate an important role for ADRP in the pathogenesis of diet-induced insulin resistance.