Regulation of Nutrient and Energy Metabolism by the Autonomic Nervous System and Food Elements

Shimazu Takashi

doi:10.4327/jsnfs.58.113

This article reviews mainly our studies conducted over 40 years or more on neural regulation of nutrient, energy metabolism and energy expenditure by effective constituents of food flavors. (1) Direct neural regulation of nutrient metabolism in the liver was demonstrated by stimulation of the ventromedial hypothalamic (VMH)-sympathetic nervous system, which-independently of hormonal effects-caused glycogenolysis by rapid activation of glycogen phosphorylase, whereas stimulation of the lateral hypothalamic (LH)-parasympathetic nerve system resulted in glycogenesis by activation of glycogen synthase in the liver. Direct neural regulation of hepatic metabolism was further verified by studying perfused liver ex vivo; the involvement of neuropeptides and certain cytokines, in addition to noradrenaline (NA), in the mechanism of nerve-signal transmission was demonstrated. (2) Extension of studies on the central nervous system regulation of energy metabolism revealed that stimulation of the VMH-sympathetic nervous system causes not only lipolysis in white and brown adipose tissue (BAT), but also lipogenesis in BAT preferentially. This indicates that the VMH-sympathetic nerves enhance triglyceride synthesis and breakdown (i.e., turnover of triglycerides), which leads to heat production and energy dissipation unique to BAT. Disorder of this regulatory system in rats decreases the body's energy expenditure and leads to obesity. (3) Skeletal muscles comprise the major working tissue involved in resting-energy metabolism. It was demonstrated that VMH stimulation also enhanced glucose uptake and utilization in the heart, skeletal muscles and BAT selectively, through mediation of direct sympathetic innervation. Analysis of the mechanism underlying this sympathetic regulation revealed that the sympathetic neurotransmitter NA enhances glucose uptake independently of insulin, but possibly via β₃-adrenergic receptors and activation of GLUT-1 glucose transporters present in the plasma membrane. Microinjection of leptin into the VMH also increased glucose uptake into skeletal muscles through sympathetic facilitation as well as β-oxidation of fatty acids through a novel signaling pathway involving AMP-kinase. (4) It has been considered that some food flavors or spices promote energy expenditure by stimulating gustatory receptors coupled with sympathetic activation. In fact, the effective components of ginger and raspberry, zingerone and raspberry ketone, were shown to have stimulatory effects on energy expenditure by increasing oxygen consumption and decreasing the respiratory quotient, resulting in amelioration of the abnormal lipid metabolism induced by ingestion of a high-fat diet.

Regulation of Nutrient and Energy Metabolism by the Autonomic Nervous System and Food Elements

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