A post-weaning obesogenic diet exacerbates the detrimental effects of maternal obesity on offspring insulin signaling in adipose tissue.
A post-weaning obesogenic diet exacerbates the detrimental effects of maternal obesity on offspring insulin signaling in adipose tissue.
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DOI：
10.1038/srep44949
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发表时间：
2017-03-24
影响因子：
4.6
通讯作者：
Ozanne SE
中科院分区：
文献类型：
--
作者：
de Almeida Faria J;Duque-Guimarães D;Carpenter AA;Loche E;Ozanne SE
此前的研究表明，母亲饮食导致的肥胖会增加子代患2型糖尿病的风险。目前的研究调查了断奶后的肥胖饮食是否夸大了母体饮食导致的脂肪组织肥胖的有害影响。母体肥胖和子代肥胖导致关键的胰岛素信号蛋白表达减少，包括胰岛素受体底物-1(IRS-1)。母亲肥胖和子代肥胖的影响通常是独立的和相加的。在所有四组后代中，IRS1的mRNA水平都是相似的，这表明在两种情况下都涉及转录后调控。母亲饮食诱导的肥胖增加了miR-126的表达，但这种miR水平不受断奶后肥胖饮食的影响。相反，断奶后的肥胖饮食与细胞因子信号-1抑制物水平的增加有关，这意味着IRS-1的降解增加是一个潜在的机制。我们的结果表明，虽然IRS-1的程序性减少与miR-126水平的增加相关，从而减少了IRS1 mRNA的翻译，但断奶后肥胖饮食对IRS-1的影响是由miR-126独立的机制介导的，包括增加IRS-1的蛋白质降解。这些不同的机制解释了为什么母体肥胖和子代肥胖的结合会对子代新陈代谢产生最显著的影响。
Previous studies have shown that maternal diet-induced obesity leads to increased risk of type 2 diabetes in offspring. The current study investigated if weaning onto an obesogenic diet exaggerated the detrimental effects of maternal diet-induced obesity in adipose tissue. Maternal obesity and offspring obesity led to reduced expression of key insulin signalling proteins, including insulin receptor substrate-1 (IRS-1). The effects of maternal obesity and offspring obesity were, generally, independent and additive. Irs1 mRNA levels were similar between all four groups of offspring, suggesting that in both cases post-transcriptional regulation was involved. Maternal diet-induced obesity increased miR-126 expression however levels of this miR were not influenced by a post-weaning obesogenic diet. In contrast, a post-weaning obesogenic diet was associated with increased levels of suppressor of cytokine signaling-1, implicating increased degradation of IRS-1 as an underlying mechanism. Our results suggest that whilst programmed reductions in IRS-1 are associated with increased levels of miR-126 and consequently reduced translation of Irs1 mRNA, the effects of a post-weaning obesogenic diet on IRS-1 are mediated by miR-126 independent mechanisms, including increased IRS-1 protein degradation. These divergent mechanisms explain why the combination of maternal obesity and offspring obesity leads to the most pronounced effects on offspring metabolism.