Citation: Yokoyama D., Tanaka W., Hashizune Y., Tandia M., Sakono M., Shimoi K., Sakakibara H. Daily consumption of monoglucosyl-rutin prevents high-fat diet-induced obesity by suppressing gastric inhibitory polypeptide secretion in mice. ABSTRACTBackground: Alpha monoglucosyl-rutin (4 G -α-D-glucopyranosyl rutin, αMR) has been shown to stimulate antioxidant defenses and anti-glycation. We evaluated the effects of αMR on body weight gain in mice. Methods:Male C57BL/6J mice were divided into four groups: Control low-fat diet, low-fat Page 354 of 371 diet + 0.5% αMR, high-fat diet, and high-fat diet + 0.5% αMR. Blood chemistry, hepatic lipids, and serum metabolic hormones and cytokines were evaluated after 4 and 13 weeks.Results: After 6 weeks, the high-fat diet group gained more weight than the low-fat diet group. Supplementing the high-fat diet with αMR suppressed weight gain by week 13.Visceral fat weight was higher in the high-fat diet group on weeks 4 and 13, while αMR supplementation inhibited increase on week 13 but not on week 4. Serum levels of gastric inhibitory polypeptide were higher in the high-fat-diet group than in the low-fat-diet group.αMR supplementation inhibited this elevation and regulated levels of serum leptin and hepatic triglycerides. Conclusion:For the first time, we demonstrated how daily consumption of αMR inhibits diet-induced visceral fat accumulation by regulating the secretion of gastric inhibitory polypeptide, which thereby prevents excess weight gain. Therefore, αMR may be a promising potential functional food. BACKGROUNDThe analysis of life insurance data reveals how obesity is associated with increased death rates, as obesity involves highly elevated risks of adverse health outcomes such as type 2 diabetes mellitus and cardiovascular disease [1,2]. Obesity can be categorized either as total obesity (body mass index ≥ 25.0 kg/m 2 ) and severe obesity (body mass index ≥ 30.0 kg/m 2 ).The prevalence of obesity worldwide has been estimated to reach 18% for men and surpass 21% for women by 2025, with severe obesity surpassing 6% in men and 9% in women in developed countries [3]. The economic burden of obesity-related diseases has been estimated to be around $48-66 billion/year in the US and £1.9-2 billion/year in the UK by 2030 [4]. Therefore, prevention of excess body weight gain and obesity is a high research priority.Weight gain results from a chronic positive energy balance, occurring when energy expenditure is lower than energy intake. Consequently, management of daily food αMR, α-monoglucosyl rutin; LFD, low-fat diet (control); HFD, high-fat diet. 1 Energy values were calculated using Atwater factors; 4 kcal/g for soluble nitrogen-free products and crude protein, and 9 kcal/g for crude lipid.

We designed an off-line combination of HPLC/photodiode array detector (PDA) and H-quantitative NMR (H-qNMR) to estimate the relative molar sensitivity (RMS) of an analyte to a reference standard. The RMS is calculated as follows: a mixture of the analyte and the reference is analyzed using H-qNMR and HPLC/PDA. The response ratio of the analyte and the reference obtained by HPLC/PDA is then corrected using the molar ratio obtained byH-qNMR. We selected methylparaben (MPB), which is a certified reference material, as the reference standard and hesperidin (Hes) and monoglucosylhesperidin (MGHes) as analytes, and the RMSs of Hes/MPB and MGHes/MPB were determined as 1.25 and 1.32, respectively. We determined the contents of Hes and MGHes in processed foods by the conventional absolute calibration method and by the internal standard method employing the RMS values with respect to MPB. The differences between the values obtained with the two methods were less than 2.0% for Hes and 3.5% for MGHes.

Water soluble α-glycosylated rutin (4G-α-D-glucopyranosyl rutin, monoglucosyl rutin, MR) was used in this study to evaluate its ability to reduce abdominal visceral fat (AVF). We conducted a study examining 66 healthy Japanese men and women with a body mass index of ≥23 and <30 kg/m 2 for 8 weeks. The subjects were randomly assigned to groups via computer random numbers as follows: MR200 group (MR 200 mg/day), MR400 group (MR 400mg/day), or placebo group. The primary outcome was change in the AVF area after 8 weeks of intervention. The secondary outcomes were effects of MR on total fat and subcutaneous fat of umbilical area, lipid-related markers, and subjective symptoms. The per-protocol set analysis involved 18 subjects in the placebo group (7 males and 11 females), 20 subjects in the MR200 group (8 males and 12 females), and 20 subjects in the MR400 group (8 males and 12 females). AVF area in both the MR200 and MR400 groups was reduced at week 8, with changes from the baseline (week 0) significantly higher than the placebo group. Additionally, the MR400 group reported improved subjective symptoms concerning being "worried about abdominal fat" at week 4 compared with the placebo group. These results indicate that the consumption of MR (200 and 400 mg/day) for 8 weeks reduced AVF.

Objective: This study aimed to investigate the suppressive effect of a single dose of water-soluble α- glycosylated rutin (monoglucosyl rutin; MR) on postprandial blood glucose elevation in healthy subjects with relatively high fasting blood glucose levels.Methods: This randomized, placebo-controlled, double-blind crossover study enrolled 34 healthy Japanese adult subjects with relatively high fasting blood glucose levels. The study period ran from November 13, 2019, to March 19, 2020. All subjects were randomly allocated to either sequence A or sequence B (n = 17 per group) using a computerized random number generator. The washout period was at least one week between periods I and II. In period I, the subjects took either MR or placebo tablets. In period II, subjects took different tablets from the ones they had taken in period I. We evaluated their blood glucose and insulin levels after glucose loading (150 g of cooked rice). The incremental area under the curve (IAUC) of the postprandial blood glucose level was determined as the primary outcome. The blood glucose and insulin levels at maximum (maximum blood concentration; Cmax), each measurement point, and IAUC of the blood insulin level after glucose loading were the secondary outcomes.Results: Out of 33 subjects, 16 in sequence A (11 men and 5 women, 54.5 ± 9.8 years) and 17 in sequence B (9 men and 8 women, 58.8 ± 9.4 years) were analyzed as a per-protocol dataset. The glucose IAUC after MR consumption was significantly lower than that of the placebo (P = 0.034). Results of the other outcomes were not observed with significant treatment effects. There were no adverse events attributable to the test foods.Conclusions: We suggest that MR has a suppressive effect on the elevation of postprandial blood glucose in healthy adults with relatively high fasting blood glucose levels.Trial registration: UMIN-CTR: UMIN000038515. Foundation: Toyo Sugar Refining Co., Ltd.Keywords: monoglucosyl rutin, blood glucose level, incremental area under the curve, α-amylase, α-glucosidase, crossover study