A post-weaning obesogenic diet exacerbates the detrimental effects of maternal obesity on offspring insulin signaling in adipose tissue

Autor(es)

Faria, Juliana de Almeida ; Duque-Guimaraes, Daniella ; Carpenter, Asha A. M. ; Loche, Elena ; Ozanne, Susan E.

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 7, MAR 24 2017.
• Citações Web of Science: 7

Resumo

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. (AU)

• Processo FAPESP: 14/20380-5 - Envolvimento dos microRNAs no processo de envelhecimento precoce causado pela obesidade
• Beneficiário: Daniella Esteves Duque Guimarães
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 14/17012-4 - A Pharmacological intervention to prevent the effects of maternal obesity on offspring adipose tissue insulin resistance
• Beneficiário: Juliana de Almeida Faria
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado