Impacts of maternal dietary fat intake on fetal development in an ovine model

Abstract

Maternal diet during pregnancy can influence fetal development and may have lasting effects on offspring health and disease risk trajectory. Intake of dietary fatty acids has been a major focus in the biomedical and epidemiological literature given concerns about the adverse effects of excessive fat intake on cardiometabolic risk and the putative health benefits of supplementing specific fats such as omega-3 polyunsaturated fatty acids (n3-PUFA). However, a thorough understanding of how maternal dietary fats impact fetal development and metabolism has been limited by ethical and logistical challenges of such studies in humans, highlighting the need for affordable large animal models of human pregnancy for evaluating these interventions. The primary aim of this dissertation was to establish the utility of the pregnant sheep for this purpose given its well-established similarities to human pregnancy in terms of gestational length, primarily singleton or twin births, and substantial mid-gestational fetal size. A series of three projects were carried out in pregnant white-faced ewes to investigate 1) the effects of maternal high-fat diet on fetal skeletal muscle metabolism; 2) the effects of maternal dietary n3-PUFA supplementation on fetoplacental fatty acid composition, transport, and metabolism; and 3) the role of placental fatty acid transporter-4 (FATP4) on fetoplacental lipid composition and metabolism. These studies demonstrate close parallels with available data from similar dietary interventions in humans and non-human primate models, including 1) a metabolic shift favoring the use of fat over carbohydrate in fetal skeletal muscle during high-fat pregnancies, and 2) enrichment of fetal tissues with n3-PUFA along with diverse impacts on lipid metabolism following maternal docosahexaenoic acid (DHA) supplementation, and 3) novel links between FATP4 expression and fetoplacental fatty acid metabolism at mid-gestation. Taken together, these studies establish the utility of an ovine model for investigating the impacts of maternal dietary fatty acid intake on fetal physiology during pregnancy, thereby facilitating future studies of the longer-term impacts of maternal diet on offspring metabolic health and disease risk.