Maternal high fat diet during pregnancy and lactation alters hepatic expression of insulin like growth factor-2 and key microRNAs in the adult offspring

Junlong Zhang,Mark Hanson,Manu Vatish,Kimberley D Bruce,Felino R Cagampang,Hendrik Lehnert,Antonio Ceriello,Fang Zhang,Christopher D Byrne,Xavier Didelot

doi:10.1186/1471-2164-10-478

Abstract

BackgroundmiRNAs play important roles in the regulation of gene functions. Maternal dietary modifications during pregnancy and gestation have long-term effects on the offspring, but it is not known whether a maternal high fat (HF) diet during pregnancy and lactation alters expression of key miRNAs in the offspring.ResultsWe studied the effects of maternal HF diet on the adult offspring by feeding mice with either a HF or a chow diet prior to conception, during pregnancy and lactation, and all offspring were weaned onto the same chow diet until adulthood. Maternal HF fed offspring had markedly increased hepatic mRNA levels of peroxisome proliferator activated receptor-alpha (ppar-alpha) and carnitine palmitoyl transferase-1a (cpt-1a) as well as insulin like growth factor-2 (Igf2). A HF diet induced up-regulation of ppar-alpha and cpt-1a expression in the wild type but not in Igf2 knock out mice. Furthermore, hepatic expression of let-7c was also reduced in maternal HF fed offspring. Among 579 miRNAs measured with microarray, ~23 miRNA levels were reduced by ~1.5-4.9-fold. Reduced expression of miR-709 (a highly expressed miRNA), miR-122, miR-192, miR-194, miR-26a, let-7a, let7b and let-7c, miR-494 and miR-483* (reduced by ~4.9 fold) was validated by qPCR. We found that methyl-CpG binding protein 2 was the common predicted target for miR-709, miR-let7s, miR-122, miR-194 and miR-26a using our own purpose-built computer program.ConclusionMaternal HF feeding during pregnancy and lactation induced co-ordinated and long-lasting changes in expression of Igf2, fat metabolic genes and several important miRNAs in the offspring.

Highlights

MiRNAs play important roles in the regulation of gene functions
We have previously shown in mice that adult offspring of dams fed a low carbohydrate, high fat and high protein diet during pregnancy and lactation but weaned onto a chow diet have reduced hepatic triglyceride levels in association with increased protein levels of key genes regulating fatty acid oxidation including carnitine palmitoyltransferase-1a (CPT-1a) and peroxisome proliferator-activated receptoralpha (PPARα) predominantly in the female offspring [33]
Maternal HF fed offspring had increased mRNA levels of ppar-α, cpt-1a and insulin like growth factor-2 (Igf2) in the liver We have previously shown that maternal high fat, high protein and low carbohydrate diet fed offspring had increased protein levels of PPARα and CPT-1a levels in the

Summary

Introduction

MiRNAs play important roles in the regulation of gene functions. MiRNAs regulate gene functions mainly through degradation of their cognate mRNAs by perfect matches with the mRNA molecules; or via inhibition of protein translation through base pairing of ~7 nucleotides (called "seed sequence") between miRNA and the 3'-untranslated region (3'-UTR) of the target mRNA molecules [8]. On the other hand one mRNA can be targeted by several miRNAs, which have additive effects in regulation of protein synthesis [12]. SMAD1 gene has two predicted binding sites for miR-26a [12], and greater suppression effects on protein translation have been observed in mRNAs containing multiple binding sites for a miRNA [13]

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