Our projects: Fetal programming of the insulin signalling pathway

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Undernutrition during fetal life is associated with programming of metabolic function, type-2 diabetes and cardiovascular disease. Evidence is mounting that maternal obesity is also a risk for adverse programming. However, exploration of the mechanistic basis of programming is challenging, as animal models of obesity generally use hypercaloric diets based upon a narrow range of pure fats or sugars. These may have effects independently of maternal body composition. A cafeteria diet (a varying panel of highly palatable foods) is known to have a programming effect on glucose homeostasis in rodents, through epigenetic modification and altered expression of the insulin-signalling pathway. Our British Heart Foundation project, funding a studentship for Grace Robinson, will utilize an established rat model of cafeteria feeding to investigate tissue sensitivity of such effects and the role of epigenetics in programming the insulin-signalling pathway. The relative contributions of maternal obesity and over-feeding to establishing metabolic and cardiovascular phenotypes will be dissected through cross-fostering and staged feeding experiments. We will evaluate vessel function using wire myography, blood pressure, glucose homeostasis and consider expression of insulin-signalling targets at the mRNA and protein level.

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