Abstract
L-Glutamate is a multifunctional amino acid involved in perception of umami taste, intermediary metabolism, and excitatory neurotransmission. Recent studies have uncovered new roles for dietary glutamate in gut-brain axis activation and energy homeostasis. Glutamate receptors and their cellular transduction molecules have recently been identified in gut epithelial cells. Stimulation of gut glutamate receptors enhances the apical expression of glutamate transporters and triggers the release of signaling molecules such as nitric oxide and serotonin. Release of these signaling molecules activates vagal afferent nerve fibers and as a result different brain regions directly or indirectly targeted by vagal inputs. More generally, evidence accumulates in support of the concept that a specific brain system, especially responsive to vagal activation, is involved in sensing the postingestive effects produced by dietary glutamate. Notably, three areas of the brain, the medial preoptic area, dorsomedial nucleus of the hypothalamus, and habenular nucleus are activated by intragastric infusions of glutamate, but not by glucose or NaCl infusions. These glutamate-specific brain responses seem to depend on vagal transmission, since complete transection of the subdiaphragmatic vagal trunks abolish monosodium glutamate (MSG)-induced brain activations but not those induced by intragastric glucose infusions. Conversely, lesions to the dopaminergic neurons of the ventral tegmental area reduce behavioral preferences for sucrose, but not for umami solutions (MSG and 5′-ribonucleotides). Consistent with these findings, gastric vagotomy specifically reduces the overall intake of MSG, and intragastric infusions of MSG at 60 mM, but not of glucose or NaCl; it also induces flavor preference learning in rats. Finally, glutamate consumption produces nutrient-specific effects on metabolism and body weight. In fact, chronic ad libitum ingestion of a palatable solution of 1% (w/v) MSG by rats reduces weight gain, fat deposition, and plasma leptin levels in comparison with ingestion of plain water. Such effects may also be vagally mediated. Taken together, these findings contribute to the growing body of evidence indicating that glutamate signaling via dedicated taste and gut receptors influences multiple physiological functions including thermoregulation and energy homeostasis.
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Abbreviations
- CS+:
-
Conditioned stimulus paired with test unconditioned stimulus
- CS-:
-
Conditioned stimulus paired with control (neutral) unconditioned stimulus
- EAAC-1:
-
Excitatory amino acid carrier-1
- fMRI:
-
Functional magnetic resonance imaging
- GIP:
-
Glucose-dependent insulinotropic polypeptide
- GLP-1:
-
Glucagon-like peptide-1
- 5-HT3R:
-
Serotonin receptor type 3
- mGluR:
-
Metabotropic glutamate receptor
- MRI:
-
Magnetic resonance imaging
- MSG:
-
Monosodium L-glutamate
- NOS:
-
Nitric oxide synthase
- NST:
-
Nucleus of the solitary tract
- TRPM5:
-
Transient receptor potential cation channel M5
- TVX:
-
Subdiaphragmatic total vagotomy
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Acknowledgment
We thank Dr. Hruda Nanda Mallick (All India Institute of Medical Sciences, New Delhi, India) and Dr. Ivan E. de Araujo (The John B. Pierce Laboratory and Yale University School of Medicine, New Haven, CT) for their valuable comments on the manuscript.
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Kondoh, T., Torii, K. (2011). Forebrain Activation by Postoral Nutritive Substances. In: Preedy, V., Watson, R., Martin, C. (eds) Handbook of Behavior, Food and Nutrition. Springer, New York, NY. https://doi.org/10.1007/978-0-387-92271-3_31
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