Appetite Regulatory Neural Circuitry in the Prenatal Testosterone Treated and Obese Ewe
Body weight and energy expenditure are regulated by the nervous systerfi. The first aim of this thesis was to characterize appetite regulatory neurons in the sheep brain which express both agouti-related protein (AgRP) and neuropeptide Y (NPY), or proopiomelanocortin (POMC) and cocaine- and amphetamine- regulated transcript (CART). We then asked whether this circuitry is altered in ewes at increased risk of obesity following prenatal testosterone (T) treatment, or in diet-induced obese ewes. Using immunocytochemistry, we found that prenatal T-treated ewes showed increased expression of the appetite stimulatory peptide, AgRP, but not the inhibitory peptide, POMC, consistent with the increased risk of obesity in these animals. In contrast, chronic diet-induced obesity led to decreased AgRP and increased POMC, suggesting compensatory mechanisms to reverse the obese state. Overall, our results suggest that distinct changes in metabolic control neurons are associated with increased predisposition, as well as expression, of obesity in adult sheep.
Prenatal programming, AgRP, POMC, Androgen Receptor, Insulin Receptor, Polycystic Ovarian Syndrome, Obesity, Sheep
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