Diet-Induced Maternal Obesity Alters Insulin Signalling in Male Mice Offspring Rechallenged with a High-Fat Diet in Adulthood.

Thaís De Fante,Débora Cristina Gustavo Vitoréli,Andressa Reginato,Márcio Alberto Torsoni,Laís Angélica Simino,Tanyara Baliani Payolla,Monique De Souza,Adriana Souza Torsoni,Marciane Milanski,Marcia B Aguila

doi:10.1371/journal.pone.0160184

Thaís De Fante, Débora Cristina Gustavo Vitoréli + Show 8 more

Open Access

https://doi.org/10.1371/journal.pone.0160184

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Journal: PloS one	Publication Date: Aug 1, 2016
Citations: 36	License type: CC BY 4.0

Affiliation: Universidade Estadual de Campinas

Abstract

Modern lifestyle has resulted in an increase in the prevalence of obesity and its comorbidities in pregnant women and the young population. It has been well established that the consumption of a high-fat diet (HFD) has many direct effects on glucose metabolism. However, it is important to assess whether maternal consumption of a HFD during critical periods of development can lead to metabolic changes in the offspring metabolism. This study evaluated the potential effects of metabolic programming on the impairment of insulin signalling in recently weaned offspring from obese dams. Additionally, we investigated if early exposure to an obesogenic environment could exacerbate the impairment of glucose metabolism in adult life in response to a HFD. Swiss female mice were fed with Standard Chow (SC) or a HFD during gestation and lactation and tissues from male offspring were analysed at d28 and d82. Offspring from obese dams had greater weight gain and higher adiposity and food intake than offspring from control dams. Furthermore, they showed impairment in insulin signalling in central and peripheral tissues, which was associated with the activation of inflammatory pathways. Adipose tissue was ultimately the most affected in adult offspring after HFD rechallenge; this may have contributed to the metabolic deregulation observed. Overall, our results suggest that diet-induced maternal obesity leads to increased susceptibility to obesity and impairment of insulin signalling in offspring in early and late life that cannot be reversed by SC consumption, but can be aggravated by HFD re-exposure.

Highlights

Worldwide, the prevalence of obesity in the younger population suggests that the intrauterine environment and lactation can contribute considerably to the development of obesity through foetal programming of offspring metabolism and energy balance [1, 2]
The introduction of a high-fat diet (HFD) from d42 to d82 (CC-HF and HH-HF mice) resulted in higher fat pad mass, food intake, glucose and insulin intolerance and glucose production in the offspring from obese dams compared to offspring from control dams
The authors showed that diet-induced maternal obesity resulted in offspring prone to metabolic disturbances that included larger adipocytes, glucose intolerance, and insulin resistance

Summary

Introduction

The prevalence of obesity in the younger population suggests that the intrauterine environment and lactation can contribute considerably to the development of obesity through foetal programming of offspring metabolism and energy balance [1, 2]. High-fat diet (HFD) has been shown to be associated with changes in lipid metabolism, increased cholesterol levels, the development of fatty liver, endoplasmic reticulum stress, impaired hypothalamic glucose metabolism, deregulation of energy homeostasis and food intake, and the deterioration of β-cell function in offspring [5, 6, 7, 8, 9, 10, 11, 12, 13]. Maternal insulin resistance in the absence of obesity can impair glucose metabolism in the offspring [14]

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