Downregulation of IRS-1 in adipose tissue of offspring of obese mice is programmed cell-autonomously through post-transcriptional mechanisms.
Downregulation of IRS-1 in adipose tissue of offspring of obese mice is programmed cell-autonomously through post-transcriptional mechanisms.
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DOI：
10.1016/j.molmet.2014.01.007
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发表时间：
2014-06
影响因子：
8.1
通讯作者：
Ozanne SE
中科院分区：
文献类型：
--
作者：
Fernandez-Twinn DS;Alfaradhi MZ;Martin-Gronert MS;Duque-Guimaraes DE;Piekarz A;Ferland-McCollough D;Bushell M;Ozanne SE
我们确定了母亲饮食诱导的肥胖对后代脂肪组织胰岛素信号传导和miRNA表达的影响，这些都是以后生活中胰岛素抵抗的病因。虽然肥胖母鼠8周龄雄性后代的身体组成和糖耐量没有失调，但血清胰岛素显著升高（p <0.05）。脂肪组织中的关键胰岛素信号蛋白下调，包括胰岛素受体、PI3K的催化（p110 β）和调节（p85 α）亚基以及AKT1和2（均p <0.05）。观察到的最大减少是IRS-1蛋白（p <0.001），其在转录后受到调节。同时，靶向IRS-1的miR-126上调（p <0.05）。这两个特征在分离的原代前脂肪细胞和体外分化的脂肪细胞中保持。因此，我们已经确定，母亲的饮食诱导的肥胖程序脂肪组织胰岛素抵抗。我们假设，在体外表型的维持强烈表明，这种机制是细胞自主的，并可能在以后的生活中驱动胰岛素抵抗。
We determined the effects of maternal diet-induced obesity on offspring adipose tissue insulin signalling and miRNA expression in the aetiology of insulin resistance in later life. Although body composition and glucose tolerance of 8-week-old male offspring of obese dams were not dysregulated, serum insulin was significantly (p<0.05) elevated. Key insulin signalling proteins in adipose tissue were down-regulated, including the insulin receptor, catalytic (p110β) and regulatory (p85α) subunits of PI3K as well as AKT1 and 2 (all p<0.05). The largest reduction observed was in IRS-1 protein (p<0.001), which was regulated post-transcriptionally. Concurrently, miR-126, which targets IRS-1, was up-regulated (p<0.05). These two features were maintained in isolated primary pre-adipocytes and differentiated adipocytes in-vitro. We have therefore established that maternal diet-induced obesity programs adipose tissue insulin resistance. We hypothesise that maintenance of the phenotype in-vitro strongly suggests that this mechanism is cell autonomous and may drive insulin resistance in later life.
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影响因子：
120.7
作者：
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通讯作者：
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作者：
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