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We study energy and glucose metabolism in healthy and obese states focusing on both the central and peripheral tissues. Our main interest is on small molecule leptin sensitizers and their metabolic effects and mechanisms of action. We have identified several small molecule compounds that have potent anti-obesity effects predominantly in hyperleptinemic diet-induced obese mice. These projects are focused on the specific mechanism of action of a distinct class of small molecule leptin sensitizers, inhibitors of histone deacetylase 6 (HDAC6), actiavtors of NRF2 (Nuclear Factor Erythroid 2-Related Factor 2), and the systemic factor(s) involved in the periphery-to-CNS communication for leptin sensitization and weight loss. We are studying the effect of HDAC6 in overall mammalian physiology in the central and peripheral tissues. We also have a drug discovery pipeline to identify small molecule non-hydroxamate HDAC6 inhibitors to develop compounds that can hopefully be used as weight loss drugs.
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