Role of Neuronal Network System in Development of the Metabolic Syndrome

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We have recently discovered that neuronal networks among organs/tissues play important roles in maintaining metabolic homeostasis in the whole body. In this study, we examined how the inter-organ neuronal networks contribute to the development of the metabolic syndrome. First, we found that hepatic ERK activation induced insulin hypersecretion and pancreatic beta cell proliferation. This liver-to-pancreas coordination is mediated by a novel neuronal network, consisting the splanchnic afferents and vagal efferents. Furthermore, this neuronal network is involved in obesity-induced hyperinsulinemia. In addition, we have found that another neuronal network originating in hepatic PPARgamma expression causes hypertension associated with obesity. Thus, this study has revealed the mechanisms underlying obesity-induced hyperinsulinemia and hypertension, which are major features of the metabolic syndrome. The mechanisms involve two types of inter-organ metabolic networks, which are potential therapeutic targets for the metabolic syndrome.