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

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.     

The Effect of Dietary Protein Imbalance during Pregnancy on the Growth,Metabolism and Circulatory Metabolome of Neonatal and Weaned Juvenile Porcine Offspring

Protein imbalance during pregnancy affects women in underdeveloped and developing countries and is associated with compromised offspring growth and an increased risk of metabolic diseases in later life. We studied in a porcine model the glucose and urea metabolism, and circulatory hormone and metabolite profile of offspring exposed during gestation, to maternal isoenergetic low–high (LP-HC), high–low (HP-LC) or adequate (AP) protein–carbohydrate ratio diets. At birth, LP-HC were lighter and the plasma acetylcarnitine to free carnitine ratios at 1 day of life was lower compared to AP offspring. Plasma urea concentrations were lower in 1 day old LP-HC offspring than HP-LC. In the juvenile period, increased insulin concentrations were observed in LP-HC and HP-LC offspring compared to AP, as was body weight from HP-LC compared to LP-HC. Plasma triglyceride concentrations were lower in 80 than 1 day old HP-LC offspring, and glucagon concentrations lower in 80 than 1 day old AP and HP-LC offspring. Plasma urea and the ratio of glucagon to insulin were lower in all 80 than 1 day old offspring. Aminoacyl-tRNA, arginine and phenylalanine, tyrosine and tryptophan metabolism, histidine and beta-alanine metabolism differed between 1 and 80 day old AP and HP-LC offspring. Maternal protein imbalance throughout pregnancy did not result in significant consequences in offspring metabolism compared to AP, indicating enormous plasticity by the placenta and developing offspring.     

Litter Size Reduction as a Model of Overfeeding during Lactation and Its Consequences for the Development of Metabolic Diseases in the Offspring

Overfeeding during lactation has a deleterious impact on the baby’s health throughout life. In humans, early overnutrition has been associated with higher susceptibility to obesity and metabolic disorders in childhood and adulthood. In rodents, using a rodent litter size reduction model (small litter) to mimic early overfeeding, the same metabolic profile has been described. Therefore, the rodent small litter model is an efficient tool to investigate the adaptive mechanisms involved in obesogenesis. Besides central and metabolic dysfunctions, studies have pointed to the contribution of the endocrine system to the small litter phenotype. Hormones, especially leptin, insulin, and adrenal hormones, have been associated with satiety, glucose homeostasis, and adipogenesis, while hypothyroidism impairs energy metabolism, favoring obesity. Behavioral modifications, hepatic metabolism changes, and reproductive dysfunctions have also been reported. In this review, we update these findings, highlighting the interaction of early nutrition and the adaptive features of the endocrine system. We also report the sex-related differences and epigenetic mechanisms. This model highlights the intense plasticity during lactation triggering many adaptive responses, which are the basis of the developmental origins of health and disease (DOHaD) concept. Our review demonstrates the complexity of the adaptive mechanisms involved in the obesity phenotype promoted by early overnutrition, reinforcing the necessity of adequate nutritional habits during lactation.