Evaluation of the relative available energy of cyclic nigerosylnigerose using breath hydrogen excretion in healthy humans.

Cyclic nigerosylnigerose (CNN) is a cyclic tetrasaccharide with properties distinct from those of other conventional cyclodextrins. We investigated the relative available energy of CNN in healthy humans. CNN digestibility was determined using brush border membrane vesicles from the small intestines of rats. CNN was not hydrolyzed by rat intestinal enzymes. To investigate breath hydrogen excretion, 13 human subjects were included in a double-blind cross-over, randomized, placebo-controlled study. The effects of CNN on hydrogen excretion were compared with those of a typical nondigestible, fermentable fructooligosaccharide (FOS). In the study participants, hydrogen excretion hardly increased upon CNN and was remarkably lower than for FOS. The available energy value was determined using the fermentability based on breath hydrogen excretion and was evaluated as 0 kcal/g for CNN. CNN was hardly metabolized and hence may be used as a low-energy dietary fiber.

Daily consumption of one teaspoon of trehalose can help maintain glucose homeostasis: a double-blind, randomized controlled trial conducted in healthy volunteers.

BACKGROUND: Trehalose is a natural disaccharide that is widely distributed. A previous study has shown that daily consumption of 10 g of trehalose improves glucose tolerance in individuals with signs of metabolic syndrome. In the present study, we determined whether a lower dose (3.3 g/day) of trehalose improves glucose tolerance in healthy Japanese volunteers. METHODS: This was a randomized, double-blind, placebo-controlled study of healthy Japanese participants (n = 50). Each consumed 3.3 g of trehalose (n = 25) or sucrose (n = 25) daily for 78 days. Their body compositions were assessed following 0, 4, 8, and 12 weeks; and serum biochemical parameters were assayed and oral 75-g glucose tolerance tests were performed at baseline and after 12 weeks. RESULTS: There were similar changes in body composition and serum biochemistry consistent with established seasonal variations in both groups, but there were no differences in any of these parameters between the two groups. However, whereas after 12 weeks of sucrose consumption, the plasma glucose concentration 2 h after a 75-g glucose load was significantly higher than the fasting concentration, after 12 weeks of trehalose consumption the fasting and 2-h plasma glucose concentrations were similar. Furthermore, an analysis of the participants with relatively high postprandial blood glucose showed that the plasma glucose concentration 2 h after a 75-g glucose load was significantly lower in the trehalose group than in the sucrose group. CONCLUSIONS: Our findings suggest that trehalose helps lower postprandial blood glucose in healthy humans with higher postprandial glucose levels within the normal range, and may therefore contribute to the prevention of pathologies that are predisposed to by postprandial hyperglycemia,, even if the daily intake of trehalose is only 3.3 g, an amount that is easily incorporated into a meal. TRIAL REGISTRATION: UMIN, UMIN000033536 . Registered 27 July 2018.

Trehalose itself plays a critical role on lipid metabolism: Trehalose increases jejunum cytoplasmic lipid droplets which negatively correlated with mesenteric adipocyte size in both HFD-fed trehalase KO and WT mice.

BACKGROUND: Trehalose is a functional disaccharide that has anti-metabolic activities such as suppression of adipocyte hypertrophy in mice and alleviation of impaired glucose tolerance in humans. Trehalase hydrolyzes trehalose in the small intestine into two glucose molecules. In this study, we investigated whether trehalose can suppress adipocyte hypertrophy in mice in the presence or absence of trehalase. METHODS: Trehalase knockout (KO) mice and wild-type (WT) mice were fed a high fat diet (HFD) and administered water with 0.3% (w/v) or without trehalose for 8 weeks. At the end of the experimental period, mesenteric adipose tissues and the small intestine were collected and the adipocyte size and proportion of cytoplasmic lipid droplets (CLDs, %) in jejunum epithelium were measured by image analysis. RESULTS: Trehalose treatment was associated with suppressed adipocyte hypertrophy in both trehalase KO and WT mice. The rate of CLDs in the jejunal epithelium was increased in both trehalase KO and WT mice given water containing trehalose relative to untreated control mice. There was a negative correlation between jejunal epithelial lipid droplet volume and mesenteric adipocyte size. Chylomicron-TG tended to be decreased in both trehalose-treated trehalase KO and WT mice. Addition of trehalose to differentiated Caco-2 cells in vitro increased intracytoplasmic lipid droplets and decreased secretion of the chylomicron marker ApoB-48. Moreover, the jejunal epithelium containing lipid droplets falled into the intestinal lumen, and triglyceride (TG) levels in feces tended to be higher in the KO/HFD/Tre group than in the KO/HFD/Water group. Since then, the accumulation of CLDs has been reported to suppress CM secretion, and along with our results, the effect of trehalose to increase jejunum CLDs may induce adipocyte hypertrophy. CONCLUSIONS: The suppression of adipocyte hypertrophy in the presence and absence of trehalase indicates that trehalose mediates effects prior to being hydrolyzed into glucose. In both trehalase KO and WT mice, trehalose treatment increased the rate of CLDs in jejunal epithelium, reduced chylomicron migration from the intestinal epithelium to the periphery, and suppressed adipocyte hypertrophy. Thus, trehalose ingestion could prevent metabolic syndrome by trapping fat droplets in the intestinal epithelium and suppressing rapid increases in chylomicrons.

Inhibitory effect of isomaltodextrin on tyrosine metabolite production in rat gut microbiota.

We examined the effect of isomaltodextrin (IMD), a soluble dietary fiber, on production of putrefactive products by intestinal bacteria using a tyrosine load test to measure phenol production in IMD-treated rats. We observed a significant increase in phenol and p-cresol concentrations in rats administered with only tyrosine, but not for rats co-administered tyrosine and IMD. To elucidate the mechanism of this effect, we analyzed the intestinal microbiota in each group and found that although IMD had no direct effect on the proportion of bacteria known to produce phenols, it did alter the balance of intestinal microbiota. The results suggested that changes in the intestinal microbiota composition reduced the metabolic capacity for tyrosine and in turn suppressed production of phenol or p-cresol, putrefactive products in the intestine.

Continuous intake of Trehalose induces white adipose tissue Browning and Enhances energy metabolism.

BACKGROUND: Trehalose is well known as a functional disaccharide with anti-metabolic activities such as suppression of adipocyte hypertrophy in mice and alleviation of impaired glucose tolerance in humans. Recently, a new type of adipocyte beige cells, involved in so-called white adipocyte tissue (WAT) browning, has received much attention as a target for adaptive thermogenesis. To clarify the relationship between adipocyte hypertrophy suppression and beige cells involved in thermogenesis, we examined the effect of trehalose on the changes in beige adipocytes in mice under normal dietary conditions. METHODS: Mice fed a normal diet were administered water containing 0.3% (W/V) trehalose for 16 weeks, 0.3% (W/V) maltose, or water without saccharide (controls). Body temperature and non-fasting blood glucose levels were measured every 3 weeks. After 16 weeks of these treatments, mesenteric and inguinal adipose tissues were collected for measuring adipocyte size, counting the number of UCP1 positive cells by image analysis, and preparing mRNA to analyze beige adipocyte-related gene expression. RESULTS: Mice administered a continuous intake of trehalose exhibited a thermogenic ability as represented by an increase in rectal temperature, which was maintained at a relatively high level from 3 to 9 weeks and was significantly higher at 15 weeks in comparison with that of the maltose group. In addition to the reduced hypertrophy of mesenteric and inguinal adipose tissues, the trehalose group showed a significant increase in the rates of beige adipocytes in each WAT in comparison with those of the maltose and the water groups. Interestingly, a negative correlation was found between the mean cell sizes of adipocytes and the rates of beige adipocytes in the WAT. Furthermore, real-time PCR showed that the expression of Cidea and Ucp1 mRNAs, which are markers for beige adipocytes in the inguinal adipose tissue, increased in the trehalose group. CONCLUSIONS: Continuous administration of trehalose to mice fed a normal diet induced WAT browning accompanied by suppression of white adipocyte hypertrophy, elevated body temperature and decreased blood glucose levels, which resulted in enhancement of energy metabolism. Therefore, we propose trehalose as a new type of thermogenic dietary component to prevent obesity by promoting WAT browning.

Glycemic, insulinemic and incretin responses after oral trehalose ingestion in healthy subjects.

BACKGROUND: Trehalose is hydrolyzed by a specific intestinal brush-border disaccharidase (trehalase) into two glucose molecules. In animal studies, trehalose has been shown to prevent adipocyte hypertrophy and mitigate insulin resistance in mice fed a high-fat diet. Recently, we found that trehalose improved glucose tolerance in human subjects. However, the underlying metabolic responses after trehalose ingestion in humans are not well understood. Therefore, we examined the glycemic, insulinemic and incretin responses after trehalose ingestion in healthy Japanese volunteers. METHODS: In a crossover study, 20 fasted healthy volunteers consumed 25 g trehalose or glucose in 100 mL water. Blood samples were taken frequently over the following 3 h, and blood glucose, insulin, active gastric inhibitory polypeptide (GIP) and active glucagon-like peptide-1 (GLP-1) levels were measured. RESULTS: Trehalose ingestion did not evoke rapid increases in blood glucose levels, and had a lower stimulatory potency of insulin and active GIP secretion compared with glucose ingestion. Conversely, active GLP-1 showed higher levels from 45 to 180 min after trehalose ingestion as compared with glucose ingestion. Specifically, active GIP secretion, which induces fat accumulation, was markedly lower after trehalose ingestion. CONCLUSIONS: Our findings indicate that trehalose may be a useful saccharide for good health because of properties that do not stimulate rapid increases in blood glucose and excessive secretion of insulin and GIP promoting fat accumulation.

Daily Intake of Trehalose Is Effective in the Prevention of Lifestyle-Related Diseases in Individuals with Risk Factors for Metabolic Syndrome.

We previously performed animal studies that suggested that trehalose potentially prevents the development of metabolic syndrome in humans. To evaluate this possibility, we examined whether trehalose suppressed the progression of insulin resistance in a placebo-controlled, double-blind trial in 34 subjects with a body mass index (BMI) ≥23. The subjects were divided into two groups and were assigned to ingest either 10 g/d of trehalose or sucrose with meals for 12 wk. During the study, body composition and blood biochemical parameters were measured at week 0, 8, and 12. These parameters were also measured 4 wk after the end of intake to confirm the washout of test substances. In the trehalose group, blood glucose concentrations after a 2-h oral glucose tolerance test significantly decreased following 12 wk of intake in comparison with baseline values (0 wk). When a stratified analysis was performed in the subjects whose percentage of truncal fat approached the high end of the normal range, the change in body weight, waist circumference, and systolic blood pressure were significantly lower in the trehalose group than in the sucrose group. Our data indicated that a daily intake of 10 g of trehalose improved glucose tolerance and progress to insulin resistance. Furthermore, these results suggested that trehalose can potentially reduce the development of metabolic syndrome and associated lifestyle-related diseases, such as type 2 diabetes.

Trehalose prevents adipocyte hypertrophy and mitigates insulin resistance in mice with established obesity.

Our group recently demonstrated that simultaneous administration of trehalose with a high-fat diet (HFD) suppresses adipocyte hypertrophy and mitigates insulin resistance in mice. For the present study, we hypothesized that similar effects of trehalose would be observed in mice with previously-established obesity. Obese mice were fed a HFD and drinking water containing 0.3 or 2.5% (weight/volume) trehalose or distilled water (DW) ad libitum for 8 wk. After 7 wk intake of a HFD and trehalose, fasting serum insulin levels and homeostasis model assessment-insulin resistance (HOMA-IR) in the 0.3% Tre/HFD group were significantly lower than those in the DW/HFD group (p<0.05). After 8 wk of treatment, mesenteric adipocytes in the 0.3% Tre/HFD group showed significantly less hypertrophy than those in the DW/HFD group. Mechanistic analysis indicated that levels of high molecular weight (HMW) adiponectin in the serum of the 0.3% Tre/HFD group were significantly higher than those in the DW/HFD group. The expression levels of insulin receptor substrate-1 (IRS-1) and insulin receptor substrate-2 (IRS-2) messenger RNA (mRNA) in muscle were also significantly increased by trehalose intake. Our data therefore suggest that administration of trehalose to obese mice mitigates insulin resistance by suppressing adipocyte hypertrophy and increasing serum HMW adiponectin, resulting in upregulation of IRS-1, and IRS-2 expression in muscle. These results further suggest that trehalose is a functional saccharide that may be used to prevent the progression of insulin resistance.

Trehalose augments osteoprotegerin production in the FHs74Int human intestinal epithelial cell line.

The disaccharide trehalose has been shown to inhibit both bone loss in ovariectomized mice and excessive osteoclastogenesis in lipopolysaccharide-injected mice. However, the mechanism of osteoclastogenesis inhibition by oral administration of trehalose is still unclear. We report here for the first time that a human intestinal epithelial cell line, FHs74Int, also produces osteoprotegerin (OPG) and that trehalose augments OPG production by this cell line. Thus, these results suggest that trehalose promotes the production of OPG by intestinal epithelial cells, which then acts on bone marrow cells, resulting in the suppression of osteoclastogenesis.