Maternal high fat diet alters metabolome in the placenta, and maternal and fetal liver altering fetal growth

Abstract

Background: Forty-nine percent of the global female population is overweight or obese. There is evidence to suggest high maternal dietary fat and salt can affect the function of the placenta, thereby affecting the growth of the fetus. In utero growth restriction has increased risks of perinatal morbidity and mortality and associations with cardiovascular disease, hypertension and diabetes in adult life. Metabolomic profiling has the potential to reveal altered maternal and fetal metabolic pathways in a diet-induced fetal growth restricted rat model. This study examines the effects of maternal high fat and/or salt on metabolism in the placenta and liver of rats. Methods: In an initial rat study, 28 virgin Sprague Dawley rats were assigned to 4 dietary groups: control (fat 10% of energy intake [EI]; high salt (salt 4%, fat 10% EI); high fat (fat 45% EI) and high fat and salt (salt 4%, fat 45% EI) 21 days prior to mating. At gestational day, 18 dams were culled; fetus and placenta weighed, maternal and fetal liver and placenta were frozen in liquid nitrogen for metabolomic analysis. The current study focussed on metabolic profiling of selected tissues using gas- and liquid-chromatography mass spectrometry and analyses by uni- and multi-variate analysis. Results: A maternal high fat diet resulted in fetal growth restriction. An effect of a maternal high fat diet was reported in maternal and fetal liver and placenta, but no effect of salt was observed. Palmitoleic acid was reduced in all tissues. Biosynthesis of unsaturated fatty acid pathway was affected. Amino acid changes were not observed except for reduced abundance of histidine in fetal liver. Fetal sex-specific effects were not seen in response to the maternal diet. Conclusions: Reduced abundance of palmitoleic acid may be a downstream effect of higher than normal levels of vascular endothelial growth factor in placenta. Delivery of essential fatty acids to fetus was not disrupted. A low level of histidine is a common theme in the fetal growth restricted fetus. This metabolic analysis adds to the increasing knowledge of the placental metabolome with reference to a maternal high fat and/or salt diet. The differences in the metabolic profiles may provide a better understanding of maternal obesity and the complex aetiology of fetal growth.