SY33-4 * NICOTINIC REGULATION OF GLUCOSE METABOLISM VIA HYPOTHALAMIC OREXIN SYSTEM

Abstract

Introduction. Mental illnesses such as depression increase the risk of metabolic disorders, although their correlation mechanisms remain unclear. Several regions of brain, including hypothalamus, play important roles in the maintenance of whole-body glucose and energy homeostasis. In addition, hypothalamic orexin system is involved in the development of nicotine addiction. We therefore investigated whether nicotine alters the metabolic activity in addition to reward activity through orexin system. Methods. Nicotine was orally administered to mice. Pyruvate tolerance test and gene expression analyses were performed to evaluate changes in hepatic gluconeogenesis. Results. Oral nicotine consumption for more than three weeks caused suppression of hepatic gluconeogenesis. Hepatic parasympathectomy abolished the effect of nicotine. In diabetic db/db mice, the nicotine treatment gradually improved glucose tolerance. Food intake and body weights were not altered. Importantly, the suppressive effect of nicotine on hepatic gluconeogenesis was disappeared in orexin knockout mice. Furthermore, hypothalamic orexin prevents the development of insulin resistance by aging, obesity, and stress. These results indicate that nicotine suppressed hepatic gluconeogenesis via hypothalamic orexin-parasympathetic routes. Conclusion. Hypothalamic orexin system appears to serve as an interface of central nicotinic actions for metabolic regulation and reward processing.