The α-glucosidase inhibitor acarbose prevents obesity and simple steatosis in sequestosome 1/A170/p62 deficient mice
The α-glucosidase inhibitor acarbose prevents obesity and simple steatosis in sequestosome 1/A170/p62 deficient mice
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DOI：
10.1111/j.1872-034x.2008.00478.x
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发表时间：
2009-05-01
影响因子：
4.2
通讯作者：
Ishii, Tetsuro
中科院分区：
文献类型：
--
作者：
Okada, Kosuke;Yanagawa, Toru;Ishii, Tetsuro
Sequestosome 1(SQSTM1)/A170/p62在膜受体介导的信号转导和自噬蛋白降解中起重要作用。尽管相关机制尚不清楚，但SQSTM1基因敲除(KO)小鼠会出现成熟期肥胖和胰岛素抵抗，从而导致II型糖尿病。当喂食标准饮食时，KO小鼠显示白色脂肪组织和肝脏中的脂肪积聚。阿卡波糖是一种α-葡萄糖苷酶抑制剂，可改善胰岛素敏感性，降低餐后高血糖，用于治疗2型糖尿病。我们研究了饮食阿卡波糖是否能预防KO小鼠肥胖和单纯性脂肪变性。从15-25周龄开始，野生型(WT)和KO小鼠分别饲喂含或不含阿卡波糖(0.8%w/w)的标准饲料。测定体重、脂肪组织和肝脏脂肪含量，并从基因表达水平评价这些组织中脂代谢的变化。阿卡波糖治疗可抑制KO小鼠体重增加和肝脏脂肪变性的发生。阿卡波糖治疗上调肝脏脂肪组织中PPARα、UCP-2和ABCA1基因的表达，以及srebp1c、PPARα和PPAR Gamma的表达。然而，在WT小鼠中，阿卡波糖治疗对体重增加和基因表达的影响很小。本研究结果表明，长期服用阿卡波糖对预防SQSTM1-KO小鼠的肥胖和单纯性脂肪变性是有效的。
Sequestosome 1 (SQSTM1)/A170/p62 plays an important role in membrane-receptor mediated signal transduction and autophagic protein degradation. Although the mechanism involved is not clear, sqstm1 gene knockout (KO) mice develop mature-onset obesity and insulin resistance, leading to type II diabetes. KO mice show accumulation of fat in white adipose tissue and the liver when fed a standard diet. Acarbose is an alpha-glucosidase inhibitor that improves insulin sensitivity and decreases postprandial hyperglycemia, and it is used to treat type 2 diabetes. We examined whether or not dietary acarbose prevented obesity and simple steatosis in KO mice.Wild-type (WT) and KO mice were fed a standard diet with or without acarbose (0.8% w/w) from 15-25 weeks of age. The body weight and the fat content of adipose tissue and the liver were measured, and changes of lipid metabolism in these tissues were assessed from gene expression.Acarbose treatment suppressed weight gain and the development of hepatic steatosis in KO mice. Acarbose treatment up-regulated hepatic expression of the ppar alpha, ucp-2, and abca1 genes, as well as srebp1c, ppar alpha, and ppar gamma in adipose tissue. In WT mice, however, acarbose treatment had little influence on weight gain and gene expression.The results of this study suggest that long-term administration of acarbose is effective for prevention of obesity and simple steatosis in SQSTM1-KO mice.