MATERNAL HIGH FAT DIET AND THE MELANOCORTIN SYSTEM IN THE OFFSPRING

Oregon Health & Science University, Portland OR

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Over the past several decades there has been a dramatic increase in childhood obesity. The general hypothesis of this proposal is that diet and metabolic health during pregnancy and the early neonatal period significantly contribute to the development of metabolic diseases in children. For these studies we developed a nonhuman primate (NHP) model of high fat/calorie diet-induced maternal obesity/diabetes that is allowing us to determine the immediate and long-term effects on body weight homeostasis in offspring. The specific focus of this proposal is the melanocortin neurons in the hypothalamus, which are critical for the homoeostatic feedback control of food intake and energy balance in response to peripheral adiposity signals. We predicted that consumption of a high fat/calorie diet during pregnancy and during nursing will cause an abnormal development of these neurons during in the fetal period, leading to a long-term reprogramming. With these developmental abnormalities, we expect the offspring to be predisposed to early onset obesity and ultimately diabetes. Finally, we will determine if feeding a healthy diet to obese/diabetic NHPs specifically during pregnancy is protective against the development of metabolic abnormalities in the offspring. With these studies, we hope to demonstrate that simply being overweight and eating a high fat diet causes metabolic disease in babies;a maternal phenotype that matches the majority of pregnancies in the United States. This information will be critical for designing a viable prevention and has enormous public health implications.