Intragastric administration of cinnamaldehyde induces changes in body temperature via TRPA1.

The transient receptor potential (TRP) channel family, including TRPA1, is known to be involved in temperature sensing and response. Previous studies have shown that intragastric administration of cinnamaldehyde (a typical TRPA1 agonist) can change body temperature, but the role of TRPA1 in this response is not clear. In this study, we found that intragastric administration of cinnamaldehyde increased in the intrascapular brown adipose tissue (IBAT) and rectal temperatures. However, this effect was not observed in TRPA1 knockout mice, suggesting that TRPA1 is involved in these temperature changes. Intravenous cinnamaldehyde also increased IBAT and rectal temperatures, only in the presence of TRPA1. We also explored the contribution of the vagus nerve to these temperature changes and found that it played a limited role. These results suggest that cinnamaldehyde can affect body temperature through TRPA1 activation, with the vagus nerve having a minor influence.

Allyl isothiocyanate increases carbohydrate oxidation through enhancing insulin secretion by TRPV1.

The transient receptor potential (TRP) V1 is a cation channel belonging to the TRP channel family and it has been reported to be involved in energy metabolism, especially glucose metabolism. While, we have previously shown that intragastric administration of allyl isothiocyanate (AITC) enhanced glucose metabolism via TRPV1, the underlying mechanism has not been elucidated. In this study, we examined the relationship between insulin secretion and the increase in carbohydrate oxidation due to AITC. Intragastric administration of AITC elevated blood insulin levels in mice and AITC directly enhanced insulin secretion from isolated islets. These observations were not reproduced in TRPV1 knockout mice. Furthermore, AITC did not increase carbohydrate oxidation in streptozotocin-treated mice. These results suggest that intragastric administration of AITC could induce insulin secretion from islets via TRPV1 and that enhancement of insulin secretion was related to the increased carbohydrate oxidation due to AITC.

Inhibition of Large Neutral Amino Acid Transporters Suppresses Kynurenic Acid Production Via Inhibition of Kynurenine Uptake in Rodent Brain.

The tryptophan metabolite, kynurenic acid (KYNA), is a preferential antagonist of the α7 nicotinic acetylcholine receptor and N-methyl-D-aspartic acid receptor at endogenous brain concentrations. Recent studies have suggested that increases of brain KYNA levels are involved in psychiatric disorders such as schizophrenia and depression, and regulation of KYNA production has become a new target for treatment of these diseases. Kynurenine (KYN), the immediate precursor of KYNA, is transported into astrocytes via large neutral amino acid transporters (LATs). In the present study, the effect of LATs regulation on KYN uptake and KYNA production was investigated in vitro and in vivo using an LATs inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH). In the in vitro study, cortical slices of rat brain were incubated with a physiological concentration of KYN and 3 µmol/L-3 mmol/L BCH. BCH inhibited KYNA production and KYN uptake in a dose-dependent manner, and their IC50 values were 90.7 and 97.4 µmol/L, respectively. In the in vivo study, mice were administered KYN (50 mg/kg BW) orally and BCH (200 mg/kg BW) intravenously. Administration of KYN increased brain KYN and KYNA levels compared with the mice treated with vehicle, whereas additional administration of BCH suppressed KYN-induced elevations in KYN and KYNA levels to 50 and 70 % in the brain. These results suggest that inhibition of LATs prevented the increase of KYNA production via blockade of KYN uptake in the brain in vitro and in vivo. LATs can be a target to modulate brain function by regulation of KYNA production in the brain.

Thermal conditions influence changes in body temperature induced by intragastric administration of capsaicin in mice.

Capsaicin has been reported to have unique thermoregulatory actions. However, changes in core temperature after the administration of capsaicin are a controversial point. Therefore, we investigated the effects of environmental thermal conditions on changes in body temperature caused by capsaicin in mice. We showed that intragastric administration of 10 and 15 mg/kg capsaicin increased tail temperature and decreased colonic temperatures in the core temperature (CT)-constant and CT-decreasing conditions. In the CT-increasing condition, 15 mg/kg capsaicin increased tail temperature and decreased colonic temperature. However, 10 mg/kg capsaicin increased colonic temperature. Furthermore, the amount of increase in tail temperature was greater in the CT-decreasing condition and lower in the CT-increasing condition, compared with that of the CT-constant condition. These findings suggest that the changes in core temperature were affected by the environmental thermal conditions and that preliminary thermoregulation state might be more important than the constancy of temperature to evaluate the effects of heat diffusion and thermogensis.

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.

Vagus nerve is involved in the changes in body temperature induced by intragastric administration of 1,8-cineole via TRPM8 in mice.

Transient Receptor Potential Melastatin 8 (TRPM8) is a cold receptor activated by mild cold temperature (<28°C). TRPM8 expressed in cutaneous sensory nerves is involved in cold sensation and thermoregulation. TRPM8 mRNA is detected in various tissues, including the gastrointestinal mucosa, and in the vagal afferent nerve. The relationship between vagal afferent nerve-specific expression of TRPM8 and thermoregulation remains unclear. In this study, we aimed to investigate whether TRPM8 expression in the vagal afferent nerve is involved in autonomic thermoregulation. We found that intragastric administration of 1,8-cineole, a TRPM8 agonist, increased intrascapular brown adipose tissue and colonic temperatures, and M8-B-treatment (TRPM8 antagonist) inhibited these responses. Intravenous administration of 1,8-cineole also showed similar effects. In vagotomized mice, the responses induced by intragastric administration of 1,8-cineole were attenuated. These results suggest that TRPM8 expressed in tissues apart from cutaneous sensory nerves are involved in autonomic thermoregulation response.

ß-Nicotinamide Mononucleotide, an Anti-Aging Candidate Compound, Is Retained in the Body for Longer than Nicotinamide in Rats.

The turnover of the oxidized form of nicotinamide adenine dinucleotide (NAD+) has attracted interest in regard to longevity. Thus, compounds that can rapidly increase the cellular NAD+ concentration have been surveyed by many researchers. Of those, ß-nicotinamide mononucleotide (ß-NMN) has been focused on. Studies on the biosynthesis of NAD+ from ß-NMN have been reported at the cellular level, but not at the whole animal level. In the present study, we investigated whether ß-NMN is superior to nicotinamide (Nam) as a precursor of NAD+ in whole animal experiments. To this end we compared the NAD+ concentration in the blood and the urinary excretion amounts of NAD+ catabolites. Rats were intraperitoneally injected with ß-NMN or Nam. After the injection, blood samples and urine samples were collected at 3-h intervals. The concentration of blood total NAD (NAD11NADH) in each sample showed no significant differences between the two groups. The urinary excretion amounts of NAD+ catabolites in the urine samples collected at 3-6 h after the injection were lower in the ß-NMN group than in the Nam group. These results suggest that ß-NMN is retained in the body for longer than Nam.

Enhancement of Fat Oxidation by Licorice Flavonoid Oil in Healthy Humans during Light Exercise.

Licorice flavonoid oil (LFO) is a new functional food ingredient consisting of hydrophobic licorice polyphenols in medium-chain triglycerides. Recent studies reported that LFO prevented and ameliorated diet-induced obesity via the regulation of lipid metabolism-related gene expression in the livers of mice and rats, while it reduced body weight in overweight human subjects by reducing total body fat. However, the direct effects of LFO on energy metabolism have not been studied in human subjects. Therefore, we investigated the effects of ingestion of LFO on energy metabolism, including fat oxidation, by measuring body surface temperature under resting conditions and respiratory gas analysis under exercise conditions in healthy humans. We showed that ingestion of a single 600 mg dose of LFO elevated body trunk skin temperature when measured in a slightly cooled air-conditioned room, and increased oxygen consumption and decreased the respiratory exchange ratio as measured by respiratory gas analysis during 40% Vo2max exercise with a cycle ergometer. Furthermore, repeated ingestion of 300 mg of LFO for 8 d decreased respiratory exchange during the recovery period following 40 min of 30% Vo2max exercise on a treadmill. These results suggest that LFO enhances fat oxidation in humans during light exercise.

Intragastric administration of allyl isothiocyanate reduces hyperglycemia in intraperitoneal glucose tolerance test (IPGTT) by enhancing blood glucose consumption in mice.

We investigated the effects of allyl isothiocyanate (AITC) on the blood glucose levels of mice using an intraperitoneal glucose tolerance test. The intragastric administration of 25 mg/kg body weight AITC reduced the increase in blood glucose level after 2 g/kg body weight glucose was given intraperitoneally, compared with that of control mice. To elucidate the mechanism responsible for the reduction, respiratory gas analysis employing (13)C-labeled glucose was performed. The intragastrically administering AITC increased (13)CO2 emission, compared to vehicle, after intraperitoneal administration of (13)C-labeled glucose. This indicated that AITC increased the utilization of exogenously administered glucose, which was excessive glucose in the blood. To examine whether transient receptor potential (TRP) channels mediated this reduction in the blood glucose levels, we used TRPA1 and TRPV1 knockout (KO) mice. Intragastrically administering AITC reduced the increase in the blood glucose level in TRPA1 KO mice but not in TRPV1 KO mice. These findings suggest that dietary AITC might reduce the increases in blood glucose levels by increasing the utilization of excessive glucose in the blood by activating TRPV1.