Fuminori Kawabata

Non-pungent capsaicin analogs (capsinoids) increase metabolic rate and enhance thermogenesis via gastrointestinal TRPV1 in mice

Capsinoids are non-pungent capsaicin analogs which increase energy expenditure like capsaicin. However, the mechanisms underlying the enhancement of their energy expenditure despite their non-pungency are poorly understood. We suggest here that capsinoids increase energy expenditure in wild-type mice, but not in transient receptor potential vanilloid 1 (TRPV1) knockout mice, implying that capsinoids increase energy expenditure via TRPV1. The jejunal administration of capsinoids to anesthetized mice raised the temperature of the colon and intrascapular brown adipose tissue. Denervation of the extrinsic nerves connected to the jejunum inhibited this temperature elevation. These findings suggest that capsinoids increase energy expenditure by activating the intestinal extrinsic nerves. Although the jejunal administration of capsinoids did not raise the tail skin temperature, an intravenous injection of capsinoids did, indicating that capsinoids could barely pass through the intestinal wall into the blood. Taken together, gastrointestinal TRPV1 may be a critical target for capsinoids to enhance energy expenditure.

Intragastric Administration of TRPV1, TRPV3, TRPM8, and TRPA1 Agonists Modulates Autonomic Thermoregulation in Different Manners in Mice

The main aim of this study was to elucidate whether thermosensitive transient receptor potential channels (thermoTRPs) play a role in controlling autonomic thermoregulation. We investigated whether the activation of certain thermoTRPs, TRPV1, TRPV3, TRPM8, and TRPA1, would induce autonomic thermoregulation by administering chemical agonists derived from spices and aroma chemicals of these channels to anesthetized mice. We discovered the following: Capsaicin, a TRPV1 agonist, enhanced thermogenesis and heat diffusion; thymol and ethyl vanillin, TRPV3 agonists, did not have any effect on thermogenesis or heat diffusion; menthol and 1,8-cineole, TRPM8 agonists, enhanced thermogenesis; and allyl isothiocyanate and cinnamaldehyde, TRPA1 agonists, enhanced thermogenesis and inhibited heat diffusion. These results suggest that these thermoTRP agonists derived from spices and aroma chemicals modulate autonomic thermoregulation, except for TRPV3 agonists. Our findings suggest the possibility that each thermoTRP is a key sensor inducing reasonable autonomic thermoregulation according to its own activated temperature range.

Off-response property of an acid-activated cation channel complex PKD1L3–PKD2L1

Ligand‐gated ion channels are important in sensory and synaptic transduction. The PKD1L3–PKD2L1 channel complex is a sour taste receptor candidate that is activated by acids. Here, we report that the proton‐activated PKD1L3–PKD2L1 ion channels have the unique ability to be activated after the removal of an acid stimulus. We refer to this property as the off‐response (previously described as a delayed response). Electrophysiological analyses show that acid‐induced responses are observed only after the removal of an acid solution at less than pH 3.0. A small increase in pH is sufficient for PKD1L3–PKD2L1 channel activation, after exposure to an acid at pH 2.5. These results indicate that this channel is a new type of ion channel—designated as an ‘off‐channel’—which is activated during stimulus application but not gated open until the removal of the stimulus. The off‐response property of PKD1L3–PKD2L1 channels might explain the physiological phenomena occurring during sour taste sensation.

Effects of CH-19 Sweet, a Non-Pungent Cultivar of Red Pepper, in Decreasing the Body Weight and Suppressing Body Fat Accumulation by Sympathetic Nerve Activation in Humans

‘CH-19 Sweet’ is a non-pungent red pepper and enhances the energy expenditure in humans in like manner to the pungent red pepper. We investigated in this study the effects of a repeated intake of CH-19 Sweet for two weeks on the body weight and body fat in humans. Changes in the autonomic nervous activity after ingesting CH-19 Sweet were also measured by a power spectral analysis. We established a new protocol which allows the precise detection of weight change in humans by using fewer subjects. These methods were used to show that the repeated intake of CH-19 Sweet reduced the body weight and suppressed body fat accumulation. Furthermore, the body weight loss due to the repeated intake of CH-19 Sweet was significantly correlated with the sympathetic nervous response after its ingestion. We propose that the repeated intake of CH-19 Sweet reduced the body weight and suppressed body fat accumulation by sympathetic nervous activation in humans.

Effects of CH-19 Sweet, a Non-Pungent Cultivar of Red Pepper, on Sympathetic Nervous Activity, Body Temperature, Heart Rate, and Blood Pressure in Humans

We investigated the changes in autonomic nervous activity, body temperature, blood pressure (BP), and heart rate (HR) after intake of the non-pungent pepper CH-19 Sweet and of hot red pepper in humans to elucidate the mechanisms of diet-induced thermogenesis (DIT) due to CH-19 Sweet. We found that CH-19 Sweet activates the sympathetic nervous system (SNS) and enhances thermogenesis as effectively as hot red pepper, ant that the heat loss effect due to CH-19 Sweet is weaker than that due to hot red pepper. Furthermore, we found that intake of CH-19 Sweet does not affect systolic BP or HR, while hot red pepper transiently elevates them. These results indicate that DIT due to CH-19 Sweet can be induced via the activation of SNS as well as hot red pepper, but that the changes in BP, HR, and heat loss effect are different between these peppers.

Intragastric administration of allyl isothiocyanate increases carbohydrate oxidation via TRPV1 but not TRPA1 in mice

The transient receptor potential (TRP) channel family is composed of a wide variety of cation-permeable channels activated polymodally by various stimuli and is implicated in a variety of cellular functions. Recent investigations have revealed that activation of TRP channels is involved not only in nociception and thermosensation but also in thermoregulation and energy metabolism. We investigated the effect of intragastric administration of TRP channel agonists on changes in energy substrate utilization of mice. Intragastric administration of allyl isothiocyanate (AITC; a typical TRPA1 agonist) markedly increased carbohydrate oxidation but did not affect oxygen consumption. To examine whether TRP channels mediate this increase in carbohydrate oxidation, we used TRPA1 and TRPV1 knockout (KO) mice. Intragastric administration of AITC increased carbohydrate oxidation in TRPA1 KO mice but not in TRPV1 KO mice. Furthermore, AITC dose-dependently increased intracellular calcium ion concentration in cells expressing TRPV1. These findings suggest that AITC might activate TRPV1 and that AITC increased carbohydrate oxidation via TRPV1.

Capsinoids, Non-Pungent Capsaicin Analogs, Reduce Body Fat Accumulation without Weight Rebound unlike Dietary Restriction in Mice

Enhancing energy expenditure and reducing energy intake are both crucial for weight control. Capsinoids, which are non-pungent capsaicin analogs, are known to suppress body fat accumulation and reduce body weight by enhancing energy expenditure in both mice and humans. However, it is poorly understood whether the suppression of body fat accumulation by capsinoids has an advantage over dietary restriction. This study shows that the oxygen consumption was increased in mice administered with capsinoids but not in dietary-restricted mice, although there was a similar suppression of body fat accumulation in both groups. The weight rebound was more notable in the dietary-restricted mice than in the mice administered with capsinoids. These results indicate that suppressing body fat accumulation by capsinoids was more beneficial than a restricted diet for maintaining body weight.

Bitter taste receptor T2R1 activities were compatible with behavioral sensitivity to bitterness in chickens.

Clarification of the mechanism of the sense of taste in chickens will provide information useful for creating and improving new feedstuffs for chickens, because the character of the taste receptors in oral tissues affects feeding behavior in animals. In this study, we focused on the sensitivity to bitterness in chickens. We cloned one of the bitter taste receptors, T2R1, from the chicken palate, constructed several biosensor-cells expressing chicken T2R1 (cT2R1), and determined a highly sensitive biosensor of cT2R1 among them. By using Ca(2+) imaging methods, we identified two agonists of cT2R1, dextromethorphan (Dex) and diphenidol (Dip). Dex was a new agonist of cT2R1 that was more potent than Dip. In a behavioral drinking study, the intake volumes of solutions of these compounds were significantly lower than that of water in chickens. These aversive concentrations were identical to the concentrations that could activate cT2R1 in a cell-based assay. These results suggest that the cT2R1 activities induced by these agonists are linked to behavioral sensitivity to bitterness in chickens.

Supplementation with eicosapentaenoic acid-rich fish oil improves exercise economy and reduces perceived exertion during submaximal steady-state exercise in normal healthy untrained men

Based on the effects of n-3 polyunsaturated fatty acids (PUFA) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on reduction of blood viscosity, we theorized that PUFA could improve aerobic performance by increasing oxygen supply to tissues. Twenty male subjects were randomly divided into two groups (n = 10): a fish oil group (FG) and a control (CG). Maximal oxygen uptake and oxygen uptake during submaximal exercise were measured using a cycle ergometer. For 8 weeks, the FG then ingested capsules containing 3.6 g/day of EPA-rich fish oil, while the CG took 3.6 g/day of a medium-chain triglyceride. After supplementation, erythrocyte EPA and DHA in the FG were significantly increased. In the FG, a negative linear correlation was detected in the change between erythrocyte EPA and whole oxygen uptake during submaximal exercise pre- and post-supplementation. The present study showed that EPA-rich fish oil supplementation improves exercise economy in humans. Graphical Abstract Supplementation with fish oil for 8 weeks improved exercise economy and reduced perceived exertion during exercise in normal healthy untrained men.

Labeling and analysis of chicken taste buds using molecular markers in oral epithelial sheets

In chickens, the sensory organs for taste are the taste buds in the oral cavity, of which there are ~240–360 in total number as estimated by scanning electron microscopy (SEM). There is not an easy way to visualize all taste buds in chickens. Here, we report a highly efficient method for labeling chicken taste buds in oral epithelial sheets using the molecular markers Vimentin and α-Gustducin. Immediate tissue fixation following incubation with sub-epithelially injected proteases enabled us to peel off whole epithelial sheets, leaving the shape and integrity of the tissue intact. In the peeled epithelial sheets, taste buds labeled with antibodies against Vimentin and α-Gustducin were easily identified and counted under a light microscope and many more taste buds, patterned in rosette-like clusters, were found than previously reported with SEM. Broiler-type, female-line males have more taste buds than other groups and continue to increase the number of taste buds over stages after hatch. In addition to ovoid-shaped taste buds, big tube-shaped taste buds were observed in the chicken using 2-photon microscopy. Our protocol for labeling taste buds with molecular markers will factilitate future mechanistic studies on the development of chicken taste buds in association with their feeding behaviors.