Differences in postingestive metabolism of glutamate and glycine between C57BL/6ByJ and 129P3/J mice

Abstract

Amino acids are essential nutrients for living organisms. There are genetic differences in voluntary consumption of amino acids among mouse strains. In two-bottle preference tests, C57BL/6ByJ (B6) mice consume more glutamate (Glu) and glycine (Gly) solutions than do 129P3/J (129) mice. To examine the role of postingestive metabolism of these amino acids in regulation of their intake, we compared metabolism of orally administered Glu and Gly in B6 and 129 mice. After administration of Glu, there were increases in circulating glucose and insulin in B6 mice, whereas 129 mice had elevated blood alanine and body temperature. After ingestion of Gly, B6 mice had increases in blood glucose, whereas there was an elevation of body temperature in 129 mice. These data suggest that B6 mice preferentially convert ingested Glu and Gly to glucose in contrast to 129 mice, which preferentially use them for thermogenesis. This study strongly supports the hypothesis that the metabolic fate of a nutrient plays an important regulatory role in control of its intake. This is the first detailed study of mouse strain differences in amino acid metabolism. Keywords gluconeogenesis; thermogenesis; blood glucose; insulin; liver AMINO ACIDS ARE ESSENTIAL to all live organisms. They serve primarily as building blocks of protein but also play many important roles in a free form [e.g., glutamic acid (Glu) and glycine (Gly) are neurotransmitters]. The major source of amino acids for animals is protein contained in ingested food. Once ingested proteins are hydrolyzed by digestive proteases, released amino acids are extensively metabolized in the small intestine (3,13,28,46). Absorbed amino acids are transported by circulation to various tissues for protein synthesis. Amino acids not used for protein synthesis are usually metabolized by the liver, where they either serve as a source of energy or are converted to glucose or ketones (5). Amino acids usually provide ~10% of the energy requirement in normal adult humans. If carbohydrate intake is insufficient or carbohydrates cannot be metabolized (e.g., because of diabetes mellitus), amino acids become a more important energy source.Not all amino acids are metabolized the same way. For example, ingested Glu is extensively metabolized in the small intestine into CO 2 , lactate, glutathione, glutamine (Gln), alanine (Ala), and several other amino acids (28,46). Under normal conditions, e.g., after consumption of proteins or monosodium glutamate (MSG) mixed with food, blood Glu does not rise because of its utilization in the intestine and liver (28,35 increase under artificial experimental conditions, when large amounts of concentrated water solutions of Glu are administered to the digestive tract. Ingested Gly is metabolized by the intestine to a lesser degree compared with Glu (46). It is used for intestinal protein synthesis and serves as an energy source and a precursor for glutathione synthesis. Dietary Glu or Gly that is not metabolized in the intestine is released into the circulation, mos...

Taste perception of monosodium glutamate and inosine monophosphate by129P3/J and C57BL/6ByJ mice

“…This conclusion is entirely consistent with two other lines of evidence: strain-specific effects of prior experience with MSG on its intake [21], and strain differences in the metabolism of orally administered MSG [38]. In the latter study [38], we found that after intragastric administration of MSG B6 mice preferentially metabolize it through gluconeogenesis, whereas the predominant process for 129 mice is thermogenesis. This suggests that a process related to gluconeogenesis of the ingested glutamate generates a rewarding stimulus, and that the glutamate-induced post-ingestive thermogenesis generates an aversive stimulus.…”

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