Physiological roles of dietary glutamate signaling via gut-brain axis due to efficient digestion and absorption

Abstract

Dietary glutamate (Glu) stimulates to evoke the umami taste, one of the five basic tastes, enhancing food palatability. But it is also the main gut energy source for the absorption and metabolism for each nutrient, thus, only a trace amount of Glu reaches the general circulation. Recently, we demonstrated a unique gut sensing system for free Glu (glutamate signaling). Glu is the only nutrient among amino acids, sugars and electrolytes that activates rat gastric vagal afferents from the luminal side specifically via metabotropic Glu receptors type 1 on mucosal cells releasing mucin and nitrite mono-oxide (NO), then NO stimulates serotonin (5HT) release at the enterochromaffin cell. Finally released 5HT stimulates 5HT3 receptor at the nerve end of the vagal afferent fiber. Functional magnetic resonance imaging (f-MRI, 4.7 T) analysis revealed that luminal sensing with 1 % (w/v) monosodium L-glutamate (MSG) in rat stomach activates both the medial preoptic area (body temperature controller) and the dorsomedial hypothalamus (basic metabolic regulator), resulting in diet-induced thermogenesis during mealing without changes of appetite for food. Interestingly, rats were forced to eat a high fat and high sugar diet with free access to 1 % (w/w) MSG and water in a choice paradigm and showed the strong preference for the MSG solution and subsequently, they displayed lower fat deposition, weight gain and blood leptin. On the other hand, these brain functional changes by the f-MRI signal after 60 mM MSG intubation into the stomach was abolished in the case of total vagotomized rats, suggesting that luminal glutamate signaling contributes to control digestion and thermogenesis without obesity.

Fig. 1

Reflex activation of vagal gastric and pancreatic nerve activity stimulated through oral, gastric, intestinal and hepatoportal glutamate sensors. Reproduced from Niijima [17]

Fig. 2

Vagal gastric afferent (VGA) responses to intragastric infusion of various amino acid solutions. Each aqueous solution (150 mmol/l, 2 ml/rat) was intubated to rat stomach, and the mean value of discharge rate above baseline at 20 min was plotted. Each column and horizontal bar represents mean ± SEM from 5 rats. **p < 0.05 versus saline (Kruskal–Wallis test). Reproduced from Uneyama et al. [24]

Fig. 3

Activated area of rat forebrain specific to the stimulation of treatment with post-oral nutrients (glucose, MSG, NaCl 60 mM and NaCl 150 mM) compared with common control images which are averaged during 10 min before administration. T-map images (bregma +2.0) depict activated brain regions at pre-administration (−5 min), 10, 20, and 40 min after the onset of intragastric infusion. Upper figure is a template image overlaid with Paxinos Atlas. ACC anterior cingulate cortex, CPu caudate putamen, ICx insular cortex, NAC nucleus accumbens. Color bar, t value. Reproduced from Tsurugizawa et al. [37]

Fig. 4

Mean intake of conditioned stimulus (filled bar CS+, flavored water with intragastric infusion of MSG, NaCl, or glucose; and open bar CS−, flavored water with intragastric infusion of water) solutions in the pre-test and test periods. Mean percent intakes of the CS+ solution are shown above the bars. Reproduced from Uematsu et al. [3]

Fig. 5

Chronological variation of the percent changes in significantly activated area in rats. Horizontal axis is elapsed time after the onset of infusion. Reproduced from Tsurugizawa et al. [37]