Malnutrition vs calorie restriction: The effects on maternal nutrient reduction in cardiac fetal mitochondrial function

Abstract

Despite the recognized beneficial effects of caloric restriction, poor maternal nutrition alters development, predisposing offspring to chronic diseases including cardiovascular disease. Mitochondrial bioenergetics are central to cardiac energy metabolism and growth. Most developmental programming studies are in polytocous altricial rodents, which show different trajectories of development and maternal nutrient burden from monotocous precocial mammals, including humans. To enable translation to human programming, we developed a primate baboon model of moderate maternal nutrient reduction (MNR) in which mothers receive 70% global nutrition eaten by controls during pregnancy and lactation and offspring often showed growth restriction. Our hypothesis is that MNR adversely impacts fetal cardiac mitochondrial metabolism and homeostasis. Our results show in the baboon model that MNR increased fetal mtDNA content and transcription of key mitochondrial genes. MNR fetal oxidative phosphorylation was decreased and mitochondria contained sparse disarranged cristae. This study provides the first association between MNR and cardiac mitochondrial remodeling in the primate fetus. Thus, disruption of cardiac mitochondrial fitness may contribute to later life cardiac dysfunction.