Roles of autonomic nervous system in inter-organ metabolic communication.

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The incidence of obesity is rising at epidemic proportions. Several mechanisms underlying the normalization of body weight following involuntary overfeeding are demonstrated ; however, the same excess amount of energy intake resulting from overfeeding does not evoke the same degree of body weight gain. We identified a novel inter-organ communication via neuronal pathway, which suppresses energy expenditure in over-nutritious state. By studying a mouse model, we found out that hepatic glucokinase expression precedes body weight gain due to high fat feeding, and showed that adenovirus-mediated expression of glucokinase in the liver suppressed energy expenditure, resulting in body weight gain. These responses are mediated by a neuronal pathway linking liver, afferent vagus, raphe palllidus, efferent sympathetic nerve, and finally brown adipose tissue, in this order. Furthermore, leptin-induced energy expenditure, primarily observed in overnutritious state, was suppressed by this pathway.