Protein Extract of a Probiotic Strain of Hafnia alvei and Bacterial ClpB Protein Improve Glucose Tolerance in Mice.

A commercial strain of Hafnia alvei (H. alvei) 4597 bacteria was shown to reduce food intake and promote weight loss, effects possibly induced by the bacterial protein ClpB, an antigen-mimetic of the anorexigenic α-melanocyte-stimulating hormone. A decrease in the basal plasma glucose levels was also observed in overweight fasted humans and mice receiving H. alvei. However, it is not known whether H. alvei influences sweet taste preference and whether its protein extract or ClpB are sufficient to increase glucose tolerance; these are the objectives tested in the present study. C57BL/6J male mice were kept under standard diet and were gavaged daily for 17 days with a suspension of H. alvei (4.5 × 107 CFU/animal) or with H. alvei total protein extract (5 µg/animal) or saline as a control. Sweet taste preference was analyzed via a brief-access licking test with sucrose solution. Glucose tolerance tests (GTT) were performed after the intraperitoneal (IP) or intragastric (IG) glucose administration at the 9th and 15th days of gavage, respectively. The expression of regulatory peptides' mRNA levels was assayed in the hypothalamus. In another experiment performed in non-treated C57BL/6J male mice, effects of acute IP administration of recombinant ClpB protein on glucose tolerance were studied by both IP- and IG-GTT. Mice treated with the H. alvei protein extract showed an improved glucose tolerance in IP-GTT but not in IG-GTT. Both groups treated with H. alvei bacteria or protein extract showed a reduction of pancreatic tissue weight but without significant changes to basal plasma insulin. No significant effects of H. alvei bacteria or its total protein extract administration were observed on the sweet taste preference, insulin tolerance and expression of regulatory peptides' mRNA in the hypothalamus. Acute administration of ClpB in non-treated mice increased glucose tolerance during the IP-GTT but not the IG-GTT, and reduced basal plasma glucose levels. We conclude that both the H. alvei protein extract introduced orally and the ClpB protein administered via IP improve glucose tolerance probably by acting at the glucose postabsorptive level. Moreover, H. alvei probiotic does not seem to influence the sweet taste preference. These results justify future testing of both the H. alvei protein extract and ClpB protein in animal models of diabetes.

Allelic variation of the Tas1r3 taste receptor gene affects sweet taste responsiveness and metabolism of glucose in F1 mouse hybrids.

In mammals, inter- and intraspecies differences in consumption of sweeteners largely depend on allelic variation of the Tas1r3 gene (locus Sac) encoding the T1R3 protein, a sweet taste receptor subunit. To assess the influence of Tas1r3 polymorphisms on feeding behavior and metabolism, we examined the phenotype of F1 male hybrids obtained from crosses between the following inbred mouse strains: females from 129SvPasCrl (129S2) bearing the recessive Tas1r3 allele and males from either C57BL/6J (B6), carrying the dominant allele, or the Tas1r3-gene knockout strain C57BL/6J-Tas1r3tm1Rfm (B6-Tas1r3-/-). The hybrids 129S2B6F1 and 129S2B6-Tas1r3-/-F1 had identical background genotypes and different sets of Tas1r3 alleles. The effect of Tas1r3 hemizygosity was analyzed by comparing the parental strain B6 (Tas1r3 homozygote) and hemizygous F1 hybrids B6 × B6-Tas1r3-/-. Data showed that, in 129S2B6-Tas1r3-/-F1 hybrids, the reduction of glucose tolerance, along with lower consumption of and lower preference for sweeteners during the initial licking responses, is due to expression of the recessive Tas1r3 allele. Hemizygosity of Tas1r3 did not influence these behavioral and metabolic traits. However, the loss of the functional Tas1r3 allele was associated with a small decline in the long-term intake and preference for sweeteners and reduction of plasma insulin and body, liver, and fat mass.

Dietary glutamate signal evokes gastric juice excretion in dogs.

BACKGROUND: Dietary-free L-glutamate (Glu) in the stomach interacts with specific Glu receptors (T1R1/T1R3 and mGluR1-8) expressed on surface epithelial and gastric gland cells. Furthermore, luminal Glu activates the vagal afferents in the stomach through the paracrine cascade including nitric oxide and serotonin (5-HT). AIM: To elucidate the role of dietary Glu in neuroendocrine control of the gastrointestinal phase of gastric secretion. METHODS: In Pavlov or Heidenhain gastric pouch dogs, secretion was measured in the pouch while monosodium glutamate (MSG) was intubated into the main stomach alone or in combination with liquid diets. RESULTS: In both experimental models, supplementation of the amino acid-rich diet with MSG (100 mmol/l) enhanced secretions of acid, pepsinogen and fluid, and elevated plasma gastrin-17. However, MSG did not affect secretion stimulated by the carbohydrate-rich diet and had no effect on basal secretion when applied in aqueous solution. Effects of MSG were abolished by denervation of the stomach and proximal small intestine with intragastrically applied lidocaine and partially suppressed with the 5-HT(3) receptor blocker granisetron. CONCLUSIONS: Supplementation of amino acid-rich liquid diets with MSG enhances gastrointestinal phase secretion through neuroendocrine pathways which are partially mediated by 5-HT. Possible mechanisms are discussed.

Effect of free dietary glutamate on gastric secretion in dogs.

The amino acid, L-glutamate, which is abundant in many foodstuffs, is a potent stimulator of gastric vagal afferents. The aim of the study was to evaluate a role of dietary glutamate in neuroendocrine control of gastric secretion of acid, pepsinogen, and fluid. In mongrel dogs with small gastric pouches surgically prepared according to Pavlov (vagally innervated) or Heidenhain (vagally decentralized), secretion in a pouch was induced by infusion into the main stomach of an amino acid-rich diet lacking glutamate (Elental) or the same diet supplemented with monosodium glutamate (MSG). Having no effect alone, MSG (100 mM) potentiated secretion induced by Elental both in Pavlov and Heidenhain models. In the Pavlov pouch, the effect of MSG was markedly reduced after i.v. injection of granisetron, an antagonist of 5-HT(3) receptors. In the Heidenhain model, MSG enhanced the stimulatory effect of pentagastrin (1 microg/kg, s.c.). In conclusion, dietary glutamate at doses not exceeding its common concentrations in foods substantially potentiates gastric phase secretion induced by stimulation of gastric mucosa with an amino acid-rich diet or by administration of pentagastrin. The effect of glutamate is partially mediated via serotonin secretion and stimulation of 5-HT(3) receptors.

Dietary monosodium glutamate enhances gastric secretion.

Dietary L-glutamate (Glu), an amino acid abundant in many foodstuffs in a free form, is able to modulate physiological functions in the stomach, including secretion and motility. Recently, specific receptors for Glu were identified in the apical membrane of chief cells in the lower region of fundic glands and in the somatostatin-secreting D-cell fraction of the gastric mucosa. This Glu-sensing system in the stomach is linked to activation of the vagal afferents. Among 20 kinds of amino acid, luminal Glu alone activated the vagal afferents in the stomach through a paracrine cascade led by nitric oxide and followed by serotonin (5-HT). In dogs with Pavlov pouches, found that supplementation of an amino acid-rich diet lacking Glu with monosodium Glu (MSG) enhanced the secretion of acid, pepsinogen, and fluid. However, MSG did not affect these secretions induced by a carbohydrate-rich diet and it had no effect on basal secretion when MSG was applied alone without the diet. Enhancement of gastric secretion by MSG was abolished by blockage of the gastric afferents using intra-gastric applied lidocaine. This effect of MSG was due in part to stimulation of 5-HT(3) receptors in the gastric mucosa.