Metabolism in different tissues/organs is considered to be systemically regulated in a coordinated manner. We have identified several neuronal networks as being involved in inter-organ metabolic communication. A broad range of metabolic information is sent from peripheral organs/tissues and transmitted by neuronal relays consisting of afferent and efferent nerves, resulting in cooperative metabolic regulation of functions, such as energy expenditure, pancreatic β cell mass, lipid metabolism and adaptive thermogenesis. These mechanisms are considered to function in maintaining metabolic homeostasis at the whole-body level, but ironically, they contribute to major clinical features of the metabolic syndrome in states of continuous excessive energy intake.
We further identified anatomical and molecular mechanisms underlying selective β cell proliferation induced by neuronal signals. Furthermore, we have succeeded in enhancing both glucose-stimulated insulin secretion and pancreatic β cell proliferation by optogenetic stimulation of vagal nerve innervating the pancreas. Thus, by taking advantage of these features of the neuronal system, metabolic homeostasis can be properly maintained at the whole-body level. The inter-organ system is a potential target of developing therapeutic strategies for metabolic disorders including diabetes.