Maternal high-protein diet modulates hepatic growth axis in weaning piglets by reprogramming the IGFBP-3 gene

Rihua Cong,Silin Ye,Yongling Hu,Hao-Yu Liu,Hui Zhang,Xiaoli Qu,Demin Cai,Xian Li

doi:10.1007/s00394-019-02097-z

Abstract

PurposeThe aim of this study was to investigate the effects of maternal high dietary protein intake on the hepatic growth axis in offspring.MethodsFourteen primiparous purebred Meishan sows were fed either a standard-protein (SP, n = 7) diet or a high-protein (HP, 150% of SP, n = 7) diet during pregnancy. Offspring (one male and one female per group, n = 14) on day 70 of the embryonic stage and on days 1, 35 and 180 after birth were selected, weighed and killed. Serum samples were analyzed for Tch, insulin and insulin-like growth factor-binding protein 3 (IGFBP-3) levels. Liver samples were analyzed for IGFBP-3 and IGF-I mRNA expression by qRT-PCR and for IGFBP-3, IGF1R and growth hormone receptor (GHR) protein expression by Western blotting. The underlying mechanism of IGFBP-3 regulation was determined by methylated DNA immunoprecipitation (MeDIP) and chromatin immunoprecipitation (ChIP).ResultsHigh-protein exposure resulted in significantly higher body and liver weights of piglets, and it increased their serum T3 and T4 levels at birth and/or at weaning. Furthermore, the IGFBP-3 protein content in the liver and serum was significantly reduced in the HP-exposed weaning piglets, whereas at the transcriptional level IGFBP-3 mRNA expression was downregulated in the livers of HP group piglets. Finally, DNA hypermethylation and higher enrichment of the histone repressive marks H3K27me3 and H3K9me3 were observed.ConclusionsTaken together, these results suggest that a maternal high-protein diet during gestation epigenetically reprograms IGFBP-3 gene expression to modulate the hepatic growth axis in weaning piglets.

Highlights

The insulin-like growth factor (IGF) system consists of two IGF ligands (IGF- I and IGF-II), two IGF receptors (IGF1R and IGF-2R), and a group of at least six IGF-binding proteins (IGFBP-1 to 6) [1]
We presented evidence demonstrating that a high-protein diet during pregnancy led to higher body and liver weights in newborns, as well as in weaning piglets
We demonstrated that liver IGF-1R protein content was increased at birth in response to high-protein exposure, indicating a stimulatory effect during the early life of offspring

Summary

Introduction

The insulin-like growth factor (IGF) system consists of two IGF ligands (IGF- I and IGF-II), two IGF receptors (IGF1R and IGF-2R), and a group of at least six IGF-binding proteins (IGFBP-1 to 6) [1]. These components are found in a variety of tissues or bodily fluids [2] and act through endocrine, paracrine, and/or autocrine modes of action [3]. It has been shown that a maternal low-protein diet (LPD) is associated with a reduced fetal liver weight in rats [12, 13]. The exact nature of these events is still unclear and warrants further exploration

Objectives

Methods

Results

Conclusion