Maternal high-fat diet modulates hepatic glucose, lipid homeostasis and gene expression in the PPAR pathway in the early life of offspring.

Jia Zheng,Zhixin Wang,Jianping Xu,Xinhua Xiao,Miao Yu,Qian Zhang

doi:10.3390/ijms150914967

Abstract

Maternal dietary modifications determine the susceptibility to metabolic diseases in adult life. However, whether maternal high-fat feeding can modulate glucose and lipid metabolism in the early life of offspring is less understood. Furthermore, we explored the underlying mechanisms that influence the phenotype. Using C57BL/6J mice, we examined the effects on the offspring at weaning from dams fed with a high-fat diet or normal chow diet throughout pregnancy and lactation. Gene array experiments and quantitative real-time PCR were performed in the liver tissues of the offspring mice. The offspring of the dams fed the high-fat diet had a heavier body weight, impaired glucose tolerance, decreased insulin sensitivity, increased serum cholesterol and hepatic steatosis at weaning. Bioinformatic analyses indicated that all differentially expressed genes of the offspring between the two groups were mapped to nine pathways. Genes in the peroxisome proliferator-activated receptor (PPAR) signaling pathway were verified by quantitative real-time PCR and these genes were significantly up-regulated in the high-fat diet offspring. A maternal high-fat diet during pregnancy and lactation can modulate hepatic glucose, lipid homeostasis, and gene expression in the PPAR signaling in the early life of offspring, and our results suggested that potential mechanisms that influences this phenotype may be related partially to up-regulate some gene expression in the PPAR signalling pathway.

Highlights

Maternal nutrition has historically been a key determinant for offspring health, and gestation is the critical time window that can affect the growth and development of offspring
The findings indicate that short term maternal HF feeding can contribute to changes in the early life of the offspring’s physiology, including a lower birth weight, increased body weight, impaired glucose tolerance, insulin resistance and increased circulating total cholesterol levels compared with the normal chow diet group
This study shows for the first time that a maternal high-fat diet only during the pregnancy and lactation periods leads to metabolic syndrome in the early life of the mice offspring through the peroxisome proliferator-activated receptor (PPAR) signaling pathway

Summary

Introduction

Maternal nutrition has historically been a key determinant for offspring health, and gestation is the critical time window that can affect the growth and development of offspring. The developmental origins of health and disease (DOHaD) hypothesis proposes that exposures during early life play a critical role in determining the risk of developing metabolic diseases in adulthood [1]. It has been widely accepted that undernutrition during early life increases the risk for intrauterine growth restriction and metabolic disease in adult life [6]. An increased number of studies have focused on maternal overnutrition during pregnancy; these studies indicated a maternal high fat diet can contribute to obesity, impaired glucose tolerance and dyslipidemia in offspring [8]

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Discussion

Conclusion