Neuropeptide Y (NPY) plays a pivotal role as a hormone that controls the feeding behavior. During hunger NPY mRNA gene expression is triggered, resulting in the production of NPY. NPY then acts in hypothalamus stimulating the feeding process. Although wealth of information is available regarding NPY and its role in hunger/feeding (1), how exactly NPY itself is controlled is poorly understood. We have two informations' that are not connected. 1) It has been reported that malony1 CoA the product of acetyl CoA carboxylase (ACC) plays a crucial role in controlling NPY production (1). 2) It has also been shown that insulin receptors are located in the brain, which upon binding with insulin stops NPY synthesis (2,3). Exactly how insulin arrests NPY synthesis in brain is not understood. After a heavy carbohydrate meal, when the glucose concentrations are high, it triggers B-cells to secrete insulin. Insulin stimulates the anabolic sequences of glycogen synthesis (in liver and muscle) and fat synthesis (in liver and adipose tissue). When the storage pools are saturated, the subsequent level of regulation is to arrest feeding. In this proposal I hypothesize that insulin crosses the blood brain barrier, binds to its receptor in the brain, and modulates the activity of ACC. ACC the forms malonyl CoA in vivo (ACC-1 and ACC- 2). ACC-2 has been proposed to be involved in the synthesis of malonyl1 CoA that plays a regulatory role during fatty acid synthesis. Thus in this study I will measure the enzyme activity of ACC-2 in the brain during hunger, well fed and under the influence of imtracerebroventricular (ICV) injection of insulin. This study will eventually result in drug designs that are targeted towards ACC-2 in controlling excess feeding.