Integration of Homeostatic and Hedonic Brain Centers in the Regulation of Feeding Behaviors

Abstract

Binge-eating disorder (BED) and obesity are major public health problems that are associated with psychosocial distress, impairments in daily function, and life-threatening co-morbidities. Both diseases are driven by maladaptive feeding behaviors, namely pathological overconsumption of high-fat food. Pathological overconsumption of high-fat food is potentiated by aberrant homeostatic feeding behavior (i.e. titration of caloric intake), which typically associates with hypothalamic brain nuclei, specifically the paraventricular nucleus of the hypothalamus (PVN) which controls food intake to maintain body weight. Additionally, pathological overconsumption of high-fat food is exacerbated by the reinforcing properties of high-fat food that drive hedonic feeding, which is mediated by the nucleus accumbens (NAc) and the ventral tegmental area (VTA). Furthermore, dysfunction of homeostatic (PVN) and hedonic (NAc, VTA) feeding circuitry is hypothesized to underlie pathological overconsumption of high-fat food. This dissertation aimed to elucidate the interconnected mechanisms of homeostatic and hedonic signaling that may underlie pathological overconsumption of high-fat food, and identified the neuropeptide receptor NMUR2 and the neurotransmitter glutamate as novel regulators of binge-type eating, intake of high-fat food, and motivation for high-fat food.