Impact of Maternal Food Restriction on Heart Proteome in Appropriately Grown and Growth-Restricted Wistar-Rat Offspring.

Andreas Zouridis,Efthymios Deligeoroglou,Anastasios Potiris,Panagiota Pervanidou,Leon Aravantinos,Makarios Eleftheriades,Spiros D Garbis,Polyxeni-Maria Sarli,Antigoni Manousopoulou

doi:10.3390/nu13020466

Abstract

Objective: Fetal growth restriction is associated with increased postnatal cardiovascular morbidity. The alterations in heart physiology and structure caused by in utero nutrient deprivation have not been extensively studied. We aim to investigate the impact of maternal food restriction on the cardiac proteome of newborn rats with normal (non-fetal growth-restricted (FGR)) and reduced (FGR) birth weight. Methods: On day 14 of gestation, 10 timed pregnant rats were randomized into two nutritional groups: (a) Standard laboratory diet and (b) 50% global food restriction. Pups born to food-restricted mothers were subdivided, based on birthweight, into fetal growth-restricted (FGR) and non-FGR, while pups born from normally nourished mothers were considered controls. Rat neonates were euthanized immediately after birth and the hearts of 11 randomly selected male offspring (n = 4 FGR, n = 4 non-FGR, n = 3 control group) were analyzed using quantitative proteomics. Results: In total, 7422 proteins were quantified (q < 0.05). Of these, 1175 were differentially expressed in FGR and 231 in non-FGR offspring vs. control with 151 common differentially expressed proteins (DEPs) between the two groups. Bioinformatics analysis of DEPs in FGR vs. control showed decreased integrin and apelin cardiac fibroblast signaling, decreased muscle contraction and glycolysis, and over-representation of a protein network related to embryonic development, and cell death and survival. Conclusion: Our study illustrates the distinct proteomic profile of FGR and non-FGR offspring of food-restricted dams underlying the importance of both prenatal adversities and birth weight in cardiac physiology and development.

Highlights

Licensee MDPI, Basel, Switzerland.Barker’s epidemiological studies in the late-80s linked poor nutrition in early life with an increased mortality rate of ischemic heart disease [1], and showed that birth weight was inversely correlated to systolic blood pressure later in life [2]
Both experimental [6] and clinical studies [7,8] show that maternal caloric restriction results in small for gestational-age fetuses (SGA) and low-birth-weight infants (LBW)
According to the current classification [9], SGA fetuses and LBW infants of undernourished mothers are considered growth-restricted (fetal growth-restricted (FGR)), as intrauterine nutrient deficiency impedes them from reaching their growth potential

Summary

Introduction

Licensee MDPI, Basel, Switzerland.Barker’s epidemiological studies in the late-80s linked poor nutrition in early life with an increased mortality rate of ischemic heart disease [1], and showed that birth weight was inversely correlated to systolic blood pressure later in life [2]. In 1991, Hales and Barker first introduced the “Thrifty phenotype hypothesis” to explain the link between the inadequate early nutrition and the development of type 2 diabetes mellitus later in life. According to this hypothesis, the thrifty phenotype could be the outcome of “fetal programming” under. Maternal nutrition is crucial for placental-fetal development [5] Both experimental [6] and clinical studies [7,8] show that maternal caloric restriction results in small for gestational-age fetuses (SGA) and low-birth-weight infants (LBW). FGR and LBW are distinct conditions, many researchers use them as synonyms to describe birthweight below the

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Results

Conclusion