Interaction between Maternal and Offspring Diet to Impair Vascular Function and Oxidative Balance in High Fat Fed Male Mice

Christopher Torrens,Giovanni E Mann,Christopher D Byrne,Kimberley D Bruce,Felino R A Cagampang,Priya Ethirajan,Mark A Hanson,Richard C M Siow,Geraldine F Clough

doi:10.1371/journal.pone.0050671

Christopher Torrens, Giovanni E Mann + Show 7 more

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https://doi.org/10.1371/journal.pone.0050671

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Abstract

AimsTo determine the impact of maternal and post-weaning consumption of a high fat diet on endothelium-dependent vasorelaxation and redox regulation in adult male mouse offspring.MethodsFemale C57BL6J mice were fed an obesogenic high fat diet (HF, 45% kcal fat) or standard chow (C, 21% kcal fat) pre-conception and throughout pregnancy and lactation. Post-weaning, male offspring were continued on the same diet as their mothers or placed on the alternative diet to give 4 dietary groups (C/C, HF/C, C/HF and HF/HF) which were studied at 15 or 30 weeks of age.ResultsThere were significant effects of maternal diet on offspring body weight (p<0.004), systolic blood pressure (p = 0.026) and endothelium-dependent relaxation to ACh (p = 0.004) and NO production (p = 0.005) measured in the femoral artery. With control for maternal diet there was also an effect of offspring post-weaning dietary fat to increase systolic blood pressure (p<0.0001) and reduce endothelium-dependent relaxation (p = 0.022) and ACh-mediated NO production (p = 0.007). There was also a significant impact of age (p<0.005). Redox balance was perturbed, with altered regulation of vascular enzymes involved in ROS/NO signalling.ConclusionsMaternal consumption of a HF diet is associated with changes in vascular function and oxidative balance in the offspring of similar magnitude to those seen with consumption of a high fat diet post-weaning. Further, this disadvantageous vascular phenotype is exacerbated by age to influence the risk of developing obesity, raised blood pressure and endothelial dysfunction in adult life.

Highlights

Over weight and obesity are associated with an increased risk of cardiovascular and metabolic disease, affecting all ages and socioeconomic groups [1]
While low levels of reactive oxygen species (ROS) play a physiological role in cell signalling and vascular function [7], enhanced production or diminished scavenging of these radicals may lead to a reduction in nitric oxide (NO) bioavailability and/or endothelial nitric oxide synthase uncoupling and increased formation of superoxide that are associated with impaired vascular function [8,9,10]
Maternal Body Weight and Body Fat Dams fed a HF diet for 4–6 weeks prior to mating, during gestation and lactation were 25% heavier (C, 26.060.93 g; HF, 31.960.83 g) and had 130% more body fat (C, 8.360.3%; HF, 1962%) at weaning compared with chow fed controls (n = 10 per group, p,0.001)

Summary

Introduction

Over weight and obesity are associated with an increased risk of cardiovascular and metabolic disease, affecting all ages and socioeconomic groups [1]. An increased prevalence of childhood obesity correlates with the increase in the number of overweight and obese women becoming pregnant [3] and there are well recognised consequences for the long term health of the children born to pregravid over weight and obese mothers [4]. Obesity is frequently related to an excessive long-term intake of fats and chronic exposure to a high fat diet is associated with an impaired endothelium-dependent vasodilation and altered oxidative balance [5,6]. The protective role of endogenous antioxidant mechanisms in cardiovascular disease and their disturbance in obesity related disorders is less clearly defined [7]

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