Brain circuitries in control of feeding behaviors:Focus on Neuropeptide Y

The modern-day food environment, with relatively easy and unlimited access to foods high in fat and sugar, contributes strongly to the etiology of obesity by disrupting peripheral and central mechanisms that control energy homeostasis. The free-choice high-fat high-sucrose diet has high clinical validity to model human diet-induced obesity. In this diet model, the orexigenic Neuropeptide Y (NPY) system is paradoxically upregulated in the hypothalamus, a key brain area involved in caloric intake and energy homeostasis. In addition, the function of key reward-related brain areas is also altered by chronic consumption of the free-choice high-fat high-sucrose diet. The first aim of this thesis was to further characterize diet-induced functional changes in the NPY system and the reward-related brain circuitry. The second aim of this thesis was to determine the neuroanatomical connection between the NPY system and key reward-related brain areas. Given that multiple brain areas express NPY, the origin of NPY that signals in the reward-related system was systematically determined. Using a combination of molecular, neuroanatomical, histological and pharmacological techniques, the studies in this thesis have provided new insight into the organization of the brain NPY system and its disruption by chronic consumption of an obesogenic diet.