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Type: Artigo
Title: A Post-weaning Obesogenic Diet Exacerbates The Detrimental Effects Of Maternal Obesity On Offspring Insulin Signaling In Adipose Tissue
Author: Faria
Juliana de Almeida; Duque-Guimaraes
Daniella; Carpenter
Asha A. M.; Loche
Elena; Ozanne
Susan E.
Abstract: 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.
Subject: Mechanisms
Editor: Nature Publishing Group
Citation: Scientific Reports. Nature Publishing Group, v. 7, p. , 2017.
Rights: aberto
Identifier DOI: 10.1038/srep44949
Date Issue: 2017
Appears in Collections:Unicamp - Artigos e Outros Documentos

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