Central Control of Energy Homeostasis & Metabolism
|Calum Avison||Kate Ellacott||Louis Muglia|
|Roger Cone||Ron Emeson||Kevin Niswender|
|Ronald Cowan||Aurelio Galli||David Zald|
A group of nine investigators is focused on the role of the central nervous system in obesity, metabolic syndrome, and reward behavior. Drs. Avison, Cowan, Galli, Niswender, and Zald form the nucleus of the group interested in the role of dopaminergic neurotransmission and reward pathways in feeding behavior. These investigators use neuroimaging, genetics, behavioral and neurophysiological methods in animal models and in humans to study the neurobiology of reward system function and its dysregulation in drug addiction and obesity.
Drs. Cone, Ellacott, Emeson, Muglia, and Niswender focus on understanding the genes involved in regulating energy homeostasis and metabolism, using model systems ranging from the zebrafish to the human. These investigators combine expertise in serotonin, leptin, insulin, CRH, and melanocortin signaling in the CNS. Many of the genes predisposing individuals to both common obesity, as well as severe early onset obesity are still being discovered. For example, only approximately 5% of severe early onset obesity can be explained by mutations in known genes such as leptin, leptin receptor, and the melanocortin-4 receptor. The Cone laboratory is using both human genetic approaches and forward genetics screening in the zebrafish to help identify these genes. This lab has also initiated a screen for positive and negative allosteric modulators of the melanocortin 4 receptor using the Vanderbilt High Throughput Screening Core. This program has identified 12 positive allosteric modulators and 19 negative modulators of MC4-R signaling, which are currently being further characterized. Agonists and antagonists of MC4-R signaling may ultimately have applications in the treatment of obesity and cachexia, respectively.