Efficacy of Long-Term Feeding of α-Glycerophosphocholine for Aging-Related Phenomena in Old Mice.

α-Glycerophosphocholine (GPC) is a natural source of choline. It reportedly prevents aging-related decline in cognitive function, but the underlying mechanism remains unclear. Although it is understood that aging influences taste sensitivity and energy regulation, whether GPC exerts antiaging effects on such phenomena requires further elucidation. Here, we used old C57BL/6J mice that were fed a GPC-containing diet, to investigate the molecular mechanisms underlying the prevention of a decline in cognitive function associated with aging and examine the beneficial effects of GPC intake on aging-related phenomena, such as taste sensitivity and energy regulation. We confirmed that GPC intake reduces the aging-related decline in the expression levels of genes related to long-term potentiation. Although we did not observe an improvement in aging-related decline in taste sensitivity, there was a notable improvement in the expression levels of ß-oxidation-associated genes in old mice. Our results suggest that the prevention of aging-related decline in cognitive function by GPC intake may be associated with the improvement of gene expression levels of long-term potentiation. Furthermore, GPC intake may positively influence lipid metabolism.

Tas2r125 functions as the main receptor for detecting bitterness of tea catechins in the oral cavity of mice.

We attempted to identify mouse bitter taste receptors, Tas2rs, that respond to tea catechins. Among representative tea catechins, avoidance behavior of mice to (-)-epicatechin gallate (ECg) was the strongest, followed by (-)-epigallocatechin gallate (EGCg). Therefore, we measured ECg response using Tas2rs-expressing cells. Among the 35 members of Tas2r family, Tas2r108, 110, 113, 125, and 144 responded to ECg. Among these receptors, Tas2r113 and 125 also responded to EGCg. Because the response profiles of Tas2r125 were consistent with the results of the behavior assays, it was considered that Tas2r125 functions as the main receptor for detecting bitterness of tea catechins in the oral cavity. To determine the involvement of Tas2rs in the physiological action of catechins, mRNA expression of 5 Tas2rs was investigated in various tissues. Because mRNA expression of Tas2r108 was observed in some tissues including the gastrointestinal tract, it may be envisaged that Tas2r108 plays a part in exerting the physiological action of ECg. Tas2r125 expression was not observed in any of the tested tissues except the circumvallate papillae. Therefore, Tas2r125 was considered to mainly function in the events of catechin reception in the oral cavity.

Sulphur-containing compounds of durian activate the thermogenesis-inducing receptors TRPA1 and TRPV1.

Durian (Durio zibethinus Murr.) is classified as a body-warming food in Indian herbalism, and its hyperthermic effect is empirically known in Southeast Asia. To investigate the mechanism underlying this effect, we focused on the thermogenesis-inducing receptors, TRPA1 and TRPV1. Durian contains sulphides similar to the TRPA1 and TRPV1 agonists of garlic. Accordingly, we hypothesized that the thermogenic effect of durian is driven by sulphide-induced TRP channel activation. To investigate our hypothesis, we measured the TRPA1 and TRPV1 activity of the sulphur-containing components of durian and quantified their content in durian pulp. These sulphur-containing components had a stronger effect on TRPA1 than TRPV1. Furthermore, sulphide content in the durian pulp was sufficient to evoke TRP channel activation and the main agonist was diethyl disulphide. From these results, we consider that the body-warming effect of durian is elicited by TRPA1 activation with its sulphides, as can be seen in spices.

Dietary zinc status reversibly alters both the feeding behaviors of the rats and gene expression patterns in diencephalon.

Nutritional status influences feeding behaviors, food preferences, and taste sensations. For example, zinc-deficient rats have been reported to show reduced and cyclic food intake patterns with increased preferences for NaCl. Although some impairments of the central nervous and endocrine systems have been speculated to be involved in these phenomena, the effects of short-term zinc deficiency on the brain have not been well examined to date. In this study, we performed a comprehensive analysis of the gene expression patterns in the rat diencephalon, which is a portion of the brain that includes the hypothalamus and thalamus, after short-term zinc deficiency and also during zinc recovery. The rats showed reduced and cyclic food intake patterns with increased salt preferences after a 10-day dietary zinc deficiency. A comparative analysis of their diencephalons using cDNA microarrays revealed that approximately 1% of the genes expressed in the diencephalons showed significantly altered expression levels. On the other hand, a 6-day zinc supplementation following the deprivation allowed for the recovery to initial food intake behaviors and salt preferences. The expression levels of most of the genes that had been altered by exposure to zinc deficient conditions were also recovered. These results show that feeding behaviors, taste preferences and gene expression patterns in the diencephalon respond quickly to changing zinc levels.

Evaluation of the bitterness of green tea catechins by a cell-based assay with the human bitter taste receptor hTAS2R39.

Catechins have a broad range of physiological functions and act as the main taste ingredient of green tea. Although catechins show a strong bitterness, the bitter taste receptor for catechins has not been fully understood. The objective of this study was to identify the receptor for the major green tea catechins such as (-)-epicatechin (EC), (-)-epicatechin gallate (ECg), (-)-epigallocatechin (EGC), and (-)-epigallocatechin gallate (EGCg). By the cell-based assay using cultured cells expressing human bitter taste receptor, a clear response of hTAS2R39-expressing cells was observed to 300µM of either ECg or EGCg, which elicit a strong bitterness in humans. The response of hTAS2R39-expressing cells to ECg was the strongest among the tested catechins, followed by EGCg. Because the cellular response to EC and EGC is much weaker than those of ECg and EGCg, galloyl groups was strongly supposed to be involved in the bitter intensity. This finding is similar to the observations of taste intensity obtained from a human sensory study. Our results suggest the participation of hTAS2R39 in the detection of catechins in humans, indicating the possibility that bitterness of tea catechins can be evaluated by using cells expressing hTAS2R39.

Activation of TRPV1 and TRPA1 by black pepper components.

We searched in this study for novel agonists of transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and transient receptor potential cation channel, subfamily A, member 1 (TRPA1) in pepper, focusing attention on 19 compounds contained in black pepper. Almost all the compounds in HEK cells heterogeneously expressed TRPV1 or TRPA1, increased the intracellular Ca(2+) concentration ([Ca(2+)](i)) in a concentration-dependent manner. Among these, piperine, isopiperine, isochavicine, piperanine, pipernonaline, dehydropipernonaline, retrofractamide C, piperolein A, and piperolein B relatively strongly activated TRPV1. The EC(50) values of these compounds for TRPV1 were 0.6-128 microM. Piperine, isopiperine, isochavicine, piperanine, piperolein A, piperolein B, and N-isobutyl-(2E,4E)-tetradeca-2,4-diamide also relatively strongly activated TRPA1, the EC(50) values of these compounds for TRPA1 were 7.8-148 microM. The Ca(2+) responses of these compounds for TRPV1 and TRPA1 were significantly suppressed by co-applying each antagonist. We identified in this study new transient receptor potential (TRP) agonists present in black pepper and found that piperine, isopiperine, isochavicine, piperanine, piperolein A, and piperolein B activated both TRPV1 and TRPA1.

Diallyl sulfides in garlic activate both TRPA1 and TRPV1.

We searched for novel agonists of TRP receptors especially for TRPA1 and TRPV1 in foods. We focused attention on garlic compounds, diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS). In TRPA1 or TRPV1 heterogeneously expressed CHO cells, all of those compounds increased [Ca(2+)](i) in concentration-dependent manner. The EC(50) values of DADS and DATS were similar to that of allyl isothiocyanate (AITC) and that of DAS was 170-fold larger than that of AITC. Maximum responses of these sulfides were equal to that of AITC. The EC(50) values of these compounds for TRPV1 were around 100 microM against that of capsaicin (CAP), 25.6 nM and maximum responses of garlic compounds were half to that of CAP. The Ca(2+) responses were significantly suppressed by co-application of antagonist. We conclude that DAS, DADS, and DATS are agonist of both TRPA1 and TRPV1 but with high affinity for TRPA1.