Obesity and its health consequences are significant both in terms of cost and quality of life. Eating and body weight are both genetically influenced while also clearly sensitive to the environment. Dietary composition is an environmental variable that can influence intake but specific mechanisms are poorly defined. Likewise, while the field has made progress in identifying key molecules and brain regions that can alter food intake, we lack good examples of how relevant dietary variables can interact with these brain systems. Vitamin D levels are known to correlate inversely with obesity rates raising the possibility that this vitamin can influence intake directly. However, no mechanisms have been proposed and little is known about vitamin D effects on neuronal function. The current proposal demonstrates a novel mouse model where low vitamin D levels amplify increases in food intake and weight seen during extended intake of a high-fat diet. Moreover, preliminary data suggest effects of high-fat diet on vitamin D signaling in mesolimbic brain reward centers. The proposed experiments will directly test the role of mesolimbic circuits in vitamin D response and characterize how the vitamin D receptor alters gene expression in neurons. This work is critical as it directly tests hypotheses and mechanisms as to how the dietary environment influences intake and body weight. PUBLIC HEALTH RELEVANCE: Obesity is major health problem in the United States and, increasing, throughout the developed world. Evidence suggests an association between vitamin D levels and body weight. The proposed experiment will explore the molecular and neural basis for these effects and thus has major implications for obesity prevention.