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Brown adipose tissue (BAT) is essential for thermoregulation and energy metabolism, converting fatty acids into thermal energy in response to cold exposure and dietary intake, thereby contributing to both cold-induced thermogenesis and diet-induced thermogenesis (DIT). Our previous research suggests that boysenberry anthocyanins (BoyACs) may activate BAT under cold conditions, and we hypothesized that BoyACs could also influence DIT through the activation of BAT. This pilot randomized, double-blind crossover trial aimed to evaluate the effects of daily intake of BoyACs on DIT in healthy adults (registration number: UMIN000047413). Twenty-two participants consumed either a boysenberry juice (BoyJ) beverage containing 61.0 mg of BoyACs or a placebo beverage daily for four weeks, with a four-week washout period separating the two interventions. Three participants withdrew during the trial, resulting in data from 19 participants being analyzed. Results showed no significant changes in DIT, defined as increase in postprandial energy expenditure, or skin temperature of BAT regions. However, a significant increase in postprandial fat oxidation was observed. No significant differences were observed in other outcomes. These results suggest that BoyJ intake does not significantly affect postprandial energy expenditure but may influence substrate utilization to promote fat oxidation. Further studies focusing on substrate utilization, particularly fat oxidation, as the primary outcome are necessary to confirm these results and fully understand the implications of BoyJ intake on energy metabolism.

Brown adipose tissue (BAT) plays an important role in energy metabolism because it uses fatty acids for thermogenesis during cold exposure. Preclinical studies found that boysenberry anthocyanins (BoyACs) activate BAT. Therefore, the aim of this preliminary study was to evaluate how BoyAC intake affects BAT in humans. We performed an open-label single-arm nonrandomized study in healthy volunteers. Before and after 4 weeks of daily consumption of 100 ml boysenberry juice (BoyJ) containing 61 mg of BoyACs, participants were assessed at 24 °C and then after 1 h of mild cold exposure (18 °C). An infrared thermography camera was used to measure skin surface temperatures in the supraclavicular BAT region (Tscv) and the non-BAT region of the upper chest (Tch). Energy metabolism was measured by indirect calorimetry. For each endpoint, we calculated Δ as the difference between values before and after cold exposure and compared the values before and after BoyJ intake. 10 volunteers participated (age: 36.1 ± 4.1, body mass index (BMI): 20.9 ± 0.6). After BoyJ intake, ΔTscv-ch was significantly higher ( p  = 0.029), but Δ energy expenditure, Δ fat oxidation, and Δ carbohydrate oxidation were not significantly different. We found a significant positive correlation between BMI and Δfat oxidation with BoyJ intake. The results indicate that 4 weeks of BoyJ intake activates cold-induced thermogenesis in the scv-BAT but does not have a significant effect on energy metabolism. BoyJ intake may increase fat oxidation during cold exposure in individuals with higher BMI. Trial registry number : UMIN000043476, 05/03/2021.

PurposeIsomaltulose is a low glycemic and insulinaemic carbohydrate available as a constituent in sports drink. However, it remains unclear whether postexercise rehydration achieved by isomaltulose drink ingestion alone differs as compared to other carbohydrates.MethodsThirteen young men performed intermittent exercise in the heat (35 °C and relative humidity 40%) to induce a state of hypohydration as defined by a 2% loss in body mass. Thereafter, participants were rehydrated by ingesting drinks equal to the volume of body mass loss with either a mixture of 3.25% glucose and 3.25% fructose, 6.5% sucrose (SUC), or 6.5% isomaltulose (ISO) within the first 30 min of a 3-h recovery. The change in plasma volume (ΔPV) from pre-exercise baseline, blood glucose, and plasma insulin concentration were assessed every 30-min.ResultsΔPV was lower in ISO as compared to SUC until 90 min of the recovery (all P ≤ 0.038) with no difference thereafter (all P ≥ 0.391). The ΔPV were paralleled by concomitant changes in blood glucose levels that were greater in ISO as compared to other drinks after 90 min of the recovery (all P ≤ 0.035). Plasma insulin secretion, which potentially enhances renal sodium reabsorption and fluid retention, did not differ between the trials (interaction, P = 0.653). ISO induced a greater net fluid volume retention as compared to SUC (P = 0.010).ConclusionWe showed that rehydration with an isomaltulose drink following exercise-heat stress induces comparable recovery of PV and a greater net fluid retention as compared to other drinks, albeit this response is delayed. The delayed water transport along with glucose absorption may modulate this response.This trial was registered in 25th Sep 2019 at https://www.umin.ac.jp/ as UMIN000038099.(249/250)

We constructed an informing system to users for the heatstroke risk using a wearable perspiration ratemeter and the users’ thirst responses. The sweating ratemeter was constructed with a capacitive humidity sensor in the ventilated capsule. The timing point for informing heatstroke risk was decided to change from positive to negative on the second derivative of sweating curve. In addition, a wearable self-identification and -information system of thirst response was constructed with a smartphone. To evaluate the validity of wearable apparatus, we aimed to conduct human experiments of 16 healthy subjects with the step up and down physical exercises. The blood and urine samples of the subjects were collected before and after the 30-min physical exercise. The concentrations of TP, Alb, and RBC increased slightly with the exercise. In contrast, the concentrations of vasopressin in all subjects remarkably increased with the exercise. In almost subjects, they identified their thirst response until several min after the informing for heatstroke risk. In conclusion, the wearable ratemeter and self-information system of thirst response were suitable for informing system of heatstroke risk. The validity of timing point for informing heatstroke risk was confirmed with changes in the thirst response and concentrations of vasopressin in blood.

The present study aims to investigate the roles of water intake in serotonin production and release in rat jejunum. We evaluated the changes in concentrations of serotonin in the portal vein and mesenteric lymph vessel induced by the intragastric administration of distilled water. The density of granules in enterochromaffin cells and the immunoreactivity of serotonin in the jejunal villi were investigated before and after water intake. The effects of intravenous administration of serotonin and/or ketanserin on mesenteric lymph flow and concentrations of albumin and IL-22 in the lymph were also addressed. Water intake increased serotonin concentration in the portal vein, but not in the mesenteric lymph vessel. The flux of serotonin through the portal vein was significantly larger than that through the mesenteric lymph vessel. Water intake decreased the density of granules in the enterochromaffin cells and increased the immunoreactivity of serotonin in the jejunal villi. The intravenous administration of serotonin increased significantly mesenteric lymph flow and the concentrations of albumin and IL-22; both were significantly reduced by the intravenous pretreatment with ketanserin. We showed that serotonin released from enterochromaffin cells by water intake was mainly transported through the portal vein. Additionally, serotonin in blood was found to increase mesenteric lymph formation with permeant albumin in the jejunal villi via the activation of 5-HT2 receptor.

PurposeIsomaltulose is a low glycemic and insulinaemic carbohydrate increasingly used as an alternative sweetener in commercial beverages. While isomaltulose beverages can improve hydration status compared to sucrose-based beverages, it remains unclear if ingestion of an isomaltulose beverage prior to exercise in the heat may improve plasma volume (PV) and thermoregulatory responses.MethodsTwelve endurance-trained men consumed a 1L carbohydrate beverage containing either 6.5%-sucrose (SUC) or 6.5%-isomaltulose (ISO) 60 min prior to 5 successive, 15-min bouts of moderate-intensity (60% of their pre-determined maximum oxygen uptake) in the heat (32 °C, 50% relative humidity), each separated by a 5 min rest. A 6th bout was performed, wherein the participant adjusted running speed to maximize distance covered within the 15-min period. The change (Δ) in PV, heart rate (HR), body core (rectal and gastrointestinal) and skin temperatures, and whole-body sweat loss were assessed during each exercise bout.ResultsIngestion of ISO induced a higher ΔPV at 4th bout only (P < 0.001) and lower HR (P = 0.032, main effect of beverage) during exercise compared to those of SUC. Body core and skin temperatures and whole-body sweat loss did not differ between conditions (all P ≥ 0.192, interaction effect). Running distance covered in final exercise bout tended to increase (~ 5%) in ISO versus SUC (P = 0.057, d = 0.64).ConclusionsRelative to a sucrose-based beverage, ISO ingestion prior to exercise in the heat reduced cardiovascular strain by preserving PV and attenuating HR, albeit with no corresponding benefit on thermoregulatory function. The former response may facilitate improvements in exercise performance.

Proper food intake is important for maintaining good health in humans. Chocolate is known to exert anti-inflammatory effects; however, the mechanisms remain unclear. In this study, we aimed to investigate the effects of cocoa butter intake on gut immunity in rats and rabbits. Cocoa butter intake increased the lymph flow, cell density, and IL-1β, IL-6 and IL-10 levels in mesenteric lymph. Clodronate, a macrophage depletion compound, significantly enhanced the release of all cytokines. The immunoreactivities of macrophage markers CD68 and F4/80 in the jejunal villi were significantly decreased with clodronate. Piceatannol, a selective cell surface ATP synthase inhibitor significantly reduced the cocoa butter intake-mediated releases of IL-1β, IL-6 and IL-10. The immunoreactivities of cell surface ATP synthase were observed in rat jejunal villi. Shear stress stimulation on the myofibroblast cells isolated from rat jejunum released ATP and carbon dioxide depended with H+ release. In rabbit in vivo experiments, cocoa butter intake increased the concentrations of ATP and H+ in the portal vein. The in vitro experiments with isolated cells of rat jejunal lamina propria the pH of 3.0 and 5.0 in the medium released significantly IL-1β and IL-6. ATP selectively released IL-10. These findings suggest that cocoa butter intake regulates the gut immunity through the release and transport of IL-1β, IL-6, and IL-10 into mesenteric lymph vessels in a negative feedback system. In addition, the H+ and ATP released from cell surface ATP synthase in jejunal villi play key roles in the cocoa butter intake–mediated regulation of gut immunity.

Abstract The higher permeability of the venules in jejunal microcirculation to albumin contributes to the increased mesenteric lymph formation. Recently, we demonstrated that water intake induced serotonin release from enterochromaffin cells in rat jejunum, serotonin of which circulated through the portal vein into blood circulation and then increased the mesenteric lymph formation. The mode of action of serotonin remains unclear. Therefore, we aimed to clarify the mechanisms involved in the regulation of the jejunal lymph formation with permeant albumin in in vivo rat experiments. We investigated the effects of intravenous administration of serotonin or water intake on the jejunal-originated lymph volume and the concentration of albumin in the lymph in the presence or absence of L-NAME. The effects of intravenous administration of L-NAME, nicardipine, A23187, and ML-7 on the lymph formation with permeant albumin were also evaluated. Serotonin or water intake significantly increased the mesenteric lymph volume with permeant albumin in the jejunal microcirculation. The serotonin- and water intake–mediated responses were significantly reduced by the pretreatment with intravenous administration of L-NAME. Intravenous administration of L-NAME itself also decreased significantly the jejunal lymph formation. Administration of A23187 and ML-7 significantly reduced the jejunal lymph formation with permeant albumin. In contrast, administration of nicardipine significantly increased the lymph formation. In conclusion, portal venous blood flow– or serotonin-mediated NO release from venular endothelial cells plays physiologically key roles in the lymph formation in rat jejunum via the extrusion of calcium ions and inactivation of MLCK in endothelial cells.

Isomaltulose is a low glycemic and insulinemic carbohydrate available as a constituent of sports drinks. However, it remains unclear whether thermoregulatory responses (sweating and cutaneous vasodilation) after isomaltulose drink ingestion differ from those of sucrose and water during exercise in a hot environment. Ten young healthy males consumed 10% sucrose, 10% isomaltulose, or water drinks. Thirty-five minutes after ingestion, they cycled for fifteen minutes at 75% peak oxygen uptake in a hot environment (30 °C, 40% relative humidity). Sucrose ingestion induced greater blood glucose concentration and insulin secretion at the pre-exercise state, compared with isomaltulose and/or water trials, with no differences during exercise in blood glucose. Change in plasma volume did not differ between the three trials throughout the experiment, but both sucrose and isomaltulose ingestions similarly increased plasma osmolality, as compared with water (main beverage effect, p = 0.040)—a key response that potentially delays the onset of heat loss responses. However, core temperature thresholds and slopes for heat loss responses were not different between the trials during exercise. These results suggest that ingestion of isomaltulose beverages induces low glycemic and insulinemic states before exercise but does not alter thermoregulatory responses during exercise in a hot environment, compared with sucrose or water.

In this review, with our current studies we demonstrated medical evidence that water and food intake are useful for IL-22-related mucosal immunity-dependent maintenance of health care. The traditional Japanese health care practices recommend daily consumption of suitable volume of water. However, immunological mechanisms that support of the traditional practices are still unsolved. We focused on type 3 innate lymphoid cells (ILC3s), because the ILC3s are mainly housed in the lamina propria of the jejunum. IL-22 released from the ILC3 is transported through mesenteric lymph in collaboration with the albumin-mediated movement of consumed water. Thus, water intake-mediated upregulation of IL-22-dependent mucosal immunity contributes to the traditional Japanese health care practices. We also reviewed current studies that food intake-mediated increase in VIP-dependent neuronal activity in the small intestine and the food intake included with tryptophan-derived metabolites may accelerate the IL-22 in ILC3s-dependent mucosal immunity and then contribute in keeping health care.