Obesity is the largest growing health problem in the western world. Despite concerted efforts and considerable advances in our scientific knowledge, the prevalence of obesity continues to rise. Obesity is a leading cause of death worldwide and is a risk factor for hypertension, diabetes, heart disease, and stroke, making both the human and monetary costs staggering. Understanding which neuropeptides in the brain and the periphery function to regulate food intake and body weight and the mechanisms by which they act are crucial for understanding both the causes and potential treatments for obesity. Interventions that result in lowered body weight over long periods of time would be extremely beneficial in combating the problem of obesity. Restraint stress has been identified as a reliable means of lowering body weight in rats and mice.
One aim of this proposal is to test the hypothesis that glucagon-like peptide-1 (GLP-1) is an important neuropeptide mediating the lowered body weight response produced by restraint stress. Additionally, since corticotropin-releasing hormone (CRH) is critically involved in mediating responses to stress, the second aim of this proposal is to test the hypothesis that increased activity of the CRH system observed after restraint stress is a result of increased GLP-1 activity directly on CRH neurons.