Endocrine Abstracts

My research focuses on the interplay of brain and adipose tissue and the elucidation of the physiology, diagnostic, and therapeutic utility of adipokines and myokines. We defined the central role these compounds play in normal physiology and pathophysiology of several diseases in humans, with the notion that such investigations will eventually lead to new treatments for metabolic and cardiovascular disease. We have also studied in-depth the role of leptin in the brain, defining the neuroendocrine and functional brain deficits in hypoleptinemia and how these, as well as deficits in fertility and bone physiology, can be corrected by the administration of leptin, which in turn acts centrally to effect these changes. This work, in addition to his work on leptin in lipodystrophy, contributed greatly to the FDA approval of leptin in the United States and Japan, with other approvals forthcoming. Additionally, we have worked on the development of INT131, a selective PPArγ modulator, which increases levels of adiponectin. This compound was recently approved by the FDA for phase III clinical trials. In light of adiponectin’s role in neuroendocrinology and metabolism, this drug is another useful translational tool that will undoubtedly lead to much-needed therapeutic applications. Extending our previous work in the field of neuroendocrinology, we are currently investigating the effect of liraglutide, a GLP-1 agonist, and lorcaserin, a serotonin 5HT-2c receptor agonist on appetite regulation and energy homeostasis. Results from these on-going studies show that liraglutide decreases attention to high fat or high calorie foods through actions in the brain, and we identified GLP-1 receptors in human brains for the first time. These exciting results will set the foundation for decoding the pathophysiological- neuroendocrine mechanisms involved in obesity and energy homeostasis, support the establishment of effective therapies for obesity, and help to identify the individuals who will benefit from them.