Diet-induced insulin resistance in mice lacking adiponectin/ACRP30
Diet-induced insulin resistance in mice lacking adiponectin/ACRP30
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DOI：
10.1038/nm724
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发表时间：
2002-07-01
期刊：
影响因子：
82.9
通讯作者：
Matsuzawa, Y
中科院分区：
文献类型：
--
作者：
Maeda, N;Shimomura, I;Matsuzawa, Y
在这里，我们研究了脂联素/ACRP 30的生物学功能，一种脂肪衍生的激素，通过破坏小鼠中编码它的基因。脂联素/ACRP 30敲除（KO）小鼠显示血浆中游离脂肪酸清除延迟，肌肉中脂肪酸转运蛋白1（FATP-1）mRNA水平低，脂肪组织中肿瘤坏死因子-α（TNF-α）mRNA水平高，血浆TNF-α浓度高。KO小鼠表现出严重的饮食诱导的胰岛素抵抗，肌肉中胰岛素受体底物1（IRS-1）相关的磷脂酰肌醇3激酶（PI 3-激酶）活性降低。病毒介导的脂联素/ACRP 30表达可逆转KO小鼠FATP-1 mRNA的减少、脂肪TNF-α mRNA的增加和饮食诱导的胰岛素抵抗。在培养的心肌细胞中，TNF-α降低FATP-1 mRNA，IRS-1相关的PI 3激酶活性和葡萄糖摄取，而脂联素增加这些参数。我们的研究结果表明，脂联素/ACRP 30缺乏和高TNF-α水平的KO小鼠减少肌肉FATP-1 mRNA和IRS-1介导的胰岛素信号转导，导致严重的饮食诱导的胰岛素抵抗。
Here we investigated the biological functions of adiponectin/ACRP30, a fat-derived hormone, by disrupting the gene that encodes it in mice. Adiponectin/ACRP30-knockout (KO) mice showed delayed clearance of free fatty acid in plasma, low levels of fatty-acid transport protein 1 (FATP-1) mRNA in muscle, high levels of tumor necrosis factor-alpha (TNF-alpha) mRNA in adipose tissue and high plasma TNF-alpha concentrations. The KO mice exhibited severe diet-induced insulin resistance with reduced insulin-receptor substrate 1 (IRS-1)-associated phosphatidylinositol 3 kinase (PI3-kinase) activity in muscle. Viral mediated adiponectin/ACRP30 expression in KO mice reversed the reduction of FATP-1 mRNA, the increase of adipose TNF-alpha mRNA and the diet-induced insulin resistance. In cultured myocytes, TNF-alpha decreased FATP-1 mRNA, IRS-1-associated PI3-kinase activity and glucose uptake, whereas adiponectin increased these parameters. Our results indicate that adiponectin/ACRP30 deficiency and high TNF-alpha levels in KO mice reduced muscle FATP-1 mRNA and IRS-1-mediated insulin signaling, resulting in severe diet-induced insulin resistance.