Perceived 6-n-Propylthiouracil (PROP) Bitterness Is Associated with Dietary Sodium Intake in Female Japanese College Students.

Despite the negative health consequences of a high sodium consumption, humans consume well above the recommended levels. This study examines whether or not the dietary intake of sodium was affected by individual variation of the perceived bitterness of 6-n-propylthiouracil (PROP), and examines the relationship between the perceived bitterness of PROP and the preferred NaCl concentration of broth. Female students (20-22 y old) were recruited from the university community. Genotypes of A49P and I296V polymorphism of the TAS2R38 bitter taste receptor were determined for each subject. Samples containing NaCl, PROP or broth in 5-mL portions were evaluated by sensory testing. The participants completed a food record for each diet. Our results indicate that the individuals perceiving PROP to be more bitter had consumed a greater amount of dietary sodium. In contrast, there was no significant positive correlation between an individual's perceived saltiness and the dietary sodium intake. Those who perceived PROP to be more bitter preferred a broth containing a higher concentration of NaCl. All of these correlations were apparent even after those subjects with TAS2R38 AI/AI homozygotes (PROP non-taster) had been excluded. In conclusion, the results of this study suggest that a factor affecting the bitter rating of PROP other than the AI/AI homozygotes of TAS2R38 contributes to the variation in sodium intake and the preference for salty food.

Luminal trypsin induces enteric nerve-mediated anion secretion in the mouse cecum.

Proteases play a diverse role in health and disease. An excessive concentration of proteases has been found in the feces of patients with inflammatory bowel disease or irritable bowel syndrome and been implicated in the pathogenesis of such disorders. This study examined the effect of the serine protease, trypsin, on intestinal epithelial anion secretion when added to the luminal side. A mucosal-submucosal sheet of the mouse cecum was mounted in Ussing chambers, and the short-circuit current (I sc) was measured. Trypsin added to the mucosal (luminal) side increased I sc with an ED50 value of approximately 10 µM. This I sc increase was suppressed by removing Cl(-) from the bathing solution. The I sc increase induced by 10-100 µM trypsin was substantially suppressed by tetrodotoxin, and partially inhibited by a neurokinin-1 receptor antagonist, but not by a muscarinic or nicotinic ACh-receptor antagonist. The trypsin-induced I sc increase was also significantly inhibited by a 5-hydroxytryptamine-3 receptor (5-HT3) antagonist and substantially suppressed by the simultaneous addition of both 5-HT3 and 5-HT4 receptor antagonists. We conclude that luminal trypsin activates the enteric reflex to induce anion secretion, 5-HT and substance P playing important mediating roles in this secreto-motor reflex. Luminal proteases may contribute to the cause of diarrhea occurring with some intestinal disorders.

The combined effects of genetic variations in the GPR120 gene and dietary fat intake on obesity risk.

Obesity is a complex multifactorial disorder resulting from the action and interaction of many genetic factors and environmental factors. Recently, it has become clear that inflammation is a key feature of obesity. Long-chain ω-3 polyunsaturated fatty acids (PUFA) have anti-inflammatory effects, and the G protein-coupled receptor GPR120 was reported to mediate the anti-inflammatory effects of ω-3 PUFAs. In addition, it was reported that GPR120 is involved in the development of obesity in mice and humans. In this study, we investigated whether common genetic variants of the GPR120 gene could influence the risk of obesity in a Japanese population. Our data suggest that the combination of common genetic variations in the GPR120 gene and dietary fat intake is a possible determinant of body mass index.

Subepithelial trypsin induces enteric nerve-mediated anion secretion by activating proteinase-activated receptor 1 in the mouse cecum.

Serine proteases are versatile signaling molecules and often exert this function by activating the proteinase-activated receptors (PAR(1)-PAR(4)). Our previous study on the mouse cecum has shown that the PAR(1)-activating peptide (AP) and PAR(2)-AP both induced electrogenic anion secretion. This secretion mediated by PAR(1) probably occurred by activating the receptor on the submucosal secretomotor neurons, while PAR(2)-mediated anion secretion probably occurred by activating the receptor on the epithelial cells. This present study was aimed at using trypsin to further elucidate the roles of serine proteases and PARs in regulating intestinal anion secretion. A mucosal-submucosal sheet of the mouse cecum was mounted in Ussing chambers, and the short-circuit current (I(sc)) was measured. Trypsin added to the serosal side increased I(sc) with an ED(50) value of approximately 100 nM. This I(sc) increase was suppressed by removing Cl(-) from the bathing solution. The I(sc) increase induced by 100 nM trypsin was substantially suppressed by tetrodotoxin, and partially inhibited by an NK(1) receptor antagonist, by a muscarinic Ach-receptor antagonist, and by 5-hydroxytryptamine-3 (5-HT(3)) and 5-HT(4) receptor antagonists. The I(sc) increase induced by trypsin was partially suppressed when the tissue had been pretreated with PAR(1)-AP, but not by a pretreatment with PAR(2)-AP. These results suggest that the serine protease, trypsin, induced anion secretion by activating the enteric secretomotor nerves. This response was initiated in part by activating PAR(1) on the enteric nerves. Serine proteases and PARs are likely to be responsible for the diarrhea occurring under intestinal inflammatory conditions.