Identification of a novel interorgan mechanism favoring energy storage in overnutrition


While body weight is essentially determined by the balance of energy intake and energy consumption, it is not necessarily the case that changes in daily food intakes and exercise directly reflect changes in body weight. In recent years, it has been revealed that numerous metabolic interactions between organs, which are organized by the brain, function as a feedback mechanism, and are involved in maintaining body weight homeostasis against excess energy intake. On the other hand, since obesity has seen an explosive increase in this age of plenty, there must be other interactions between organs working as feedforward mechanisms favoring weight gain. However, no such interaction has yet been demonstrated. Recently, we discovered a new interorgan neural network, from the liver, which may represent the feedforward mechanism.1 Under conditions of excessive energy intake, changes in glucose metabolism occur in the liver with increased expression of hepatic glucokinase (GK) and the induction of neuronal signal transmission via the afferent vagus nerve. These signals are received by the medulla and result in inactivation of sympathetic nerve to brown adipose tissue (BAT), thereby suppressing thermogenesis in BAT and promoting adiposity. Furthermore, the efficacy of the liver-to-BAT interaction differs among mouse strains and these differences may contribute to determining the obesity predispositions of various strains. In conclusion, this novel interorgan neuronal relay system functions to suppress energy expenditure when energy intake is increased, and thus, is considered to be a thrifty mechanism operating on the whole body level. During periods when sufficient food was not always available, this system worked in favor of survival. However, in the current age of plenty, it is assumed to work as a mechanism flipping a metabolic switch toward obesity.

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S Tsukita, T Yamada, K Uno, K Takahashi, K Kaneko, Y Ishigaki, et al. Hepatic glucokinase modulates obesity predisposition by regulating BAT thermogenesis via neural signals. Cell Metab 2012; 16: 825- 32.
PMID: 23217261 DOI: 10.1016/j.cmet.2012.11.006

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Identification of a novel interorgan mechanism favoring energy storage in overnutrition