Appetite suppressants

Abstract

The present invention aims to provide a food (including foods for specified health uses and foods with functional claims) or pharmaceutical product containing rare sugars as an active ingredient that can be used for novel applications. [Solution] The above problem is achieved by a food composition or pharmaceutical composition containing D-allose, D-sorbose, or derivatives thereof as an active ingredient, for the prevention, improvement, or treatment of symptoms or diseases selected from the group consisting of obesity due to overeating, diabetes or elevated blood glucose levels resulting from obesity due to overeating, and hepatic fat accumulation resulting from obesity due to overeating.

Description

Technical Field

[0001] The present invention relates to a novel appetite suppressant.

Background Art

[0002] Ordinary sugars such as sucrose and its constituent components, D-glucose and D-fructose, are abundantly present in nature and are widely used as sweeteners due to their energy content and sweetness intensity. These sugars are prone to overconsumption, and overconsumption is known to cause metabolic disorders such as obesity, diabetes, and dyslipidemia. On the other hand, monosaccharides and their derivatives that are present only in small amounts in nature are collectively called rare sugars. Many rare sugars have poor metabolism in the body, so they have low calories while having sweetness. Therefore, rare sugars are expected to contribute to preventing excessive energy intake as sweeteners and may play a role in preventing lifestyle-related diseases such as obesity and diabetes (Non-Patent Document 1). Regarding the physiological functions such as the anti-obesity effect and anti-diabetes effect of rare sugar syrup, which is a mixed syrup containing 45% D-glucose, 29% D-fructose, 5% D-allose, 5% D-sorbose, 2% D-tagatose, 1% D-allose, and 13% other sugars, many studies have been reported in animal experiments and human experiments (Non-Patent Documents 2 and 3). However, the mechanism of action underlying these effects and the effects of individual rare sugars have not yet been fully clarified.

[0003] Glucagon-like peptide-1 (GLP-1) is a peptide hormone secreted from enteroendocrine L cells, and its secretion is enhanced after meals. This endogenous GLP-1 has a very short half-life because it is decomposed by dipeptidyl peptidase-4, but there are reports that it plays an important role in suppressing food intake and improving glucose tolerance by acting on the afferent vagus nerve distributed in the vicinity of the digestive tract (Non-Patent Document 4). The inventors previously reported that the rare sugar D-allulose promotes the release of GLP-1, thereby preventing obesity caused by overeating (Patent Document 1, Non-Patent Document 5). However, many aspects of the effects of other rare sugars, D-sorbose and D-allose, on GLP-1 secretion and feeding behavior remain unclear. [Prior art documents] [Patent Documents]

[0004] [Patent Document 1] WO2017 / 018500 [Non-patent literature]

[0005] [Non-Patent Document 1] Nutrition Reviews, Vol.80(2) 255-270 (2022) [Non-Patent Document 2] Journal of Agricultural and Food Chemistry, 65, 2888-2894 (2017) [Non-Patent Document 3] Open Journal of Preventive Medicine, 1, 66-71 (2011) [Non-Patent Document 4] Molecular Metabolism, 30, 72-130 (2019) [Non-Patent Document 5] Nature Communications, 9:113 (2018) [Overview of the project] [Problems that the invention aims to solve]

[0006] The present invention aims to provide a food (including Foods for Specified Health Uses and Foods with Function Claims) or pharmaceutical product containing rare sugars as an active ingredient that can be used for novel applications. [Means for solving the problem]

[0007] The present inventors have discovered that D-allose, D-sorbose, or their derivatives have an appetite-suppressing effect. The inventors also found that D-allose or its derivatives do not promote the secretion of GLP-1 (glucagon-like peptide-1), which has been reported to play an important role in suppressing appetite, and that the appetite-suppressing effect is not reduced by antagonism of the GLP-1 receptor. On the other hand, they found that D-sorbose or its derivatives promote GLP-1 secretion and reduce the appetite-suppressing effect by antagonizing the GLP-1 receptor. The present invention provides the following: [1] An appetite suppressant or a postprandial satiety-sustaining agent containing D-allose, D-sorbose, or derivatives thereof as an active ingredient. [2] An appetite suppressant or postprandial satiety-sustaining agent according to [1] above, comprising D-allose or a derivative thereof as an active ingredient, wherein the appetite suppressant effect or postprandial satiety-sustaining effect is not reduced by GLP-1 receptor antagonism. [3] An appetite suppressant or postprandial satiety-sustaining agent according to [1] above, comprising D-sorbose or a derivative thereof as an active ingredient, wherein the appetite suppressant effect or postprandial satiety-sustaining effect is reduced by GLP-1 receptor antagonism. [4] A GLP-1 secretion enhancer containing D-sorbose or a derivative thereof as an active ingredient. [5] A pharmaceutical composition comprising D-allose, D-sorbose, or derivatives thereof as an active ingredient, for the prevention, improvement, or treatment of symptoms or diseases selected from the group consisting of obesity due to overeating, diabetes mellitus caused by obesity due to overeating, and hepatic fat accumulation caused by obesity due to overeating. [6] A food composition comprising D-allose, D-sorbose, or derivatives thereof as an active ingredient, for uses selected from the group consisting of appetite suppression, sustained satiety, prevention or improvement of obesity caused by overeating, prevention or suppression of elevated blood glucose levels caused by obesity, and prevention or suppression of hepatic fat accumulation caused by obesity. [7] A pharmaceutical composition for the prevention, improvement, or treatment of symptoms or diseases selected from the group consisting of obesity due to overeating, diabetes mellitus resulting from obesity due to overeating, and hepatic fat accumulation resulting from obesity due to overeating, comprising an appetite suppressant or a satiety-sustaining agent after a meal according to any one of [1] to [3] above, or a GLP-1 secretion-promoting agent according to [4] above. [8] A food composition for use selected from the group consisting of appetite suppression, sustained satiety, prevention or improvement of binge eating obesity, prevention or suppression of elevated blood glucose levels caused by binge eating obesity, and prevention or suppression of hepatic fat accumulation caused by binge eating obesity, comprising an appetite suppressant or satiety-sustaining agent according to any one of [1] to [3] above, or a GLP-1 secretion-promoting agent according to [4] above. [Effects of the Invention]

[0008] The present invention provides a novel appetite suppressant or post-meal satiety-sustaining agent. By ingesting the appetite suppressant or post-meal satiety-sustaining agent of the present invention, appetite suppression or sustained satiety can be achieved. Furthermore, the food composition or pharmaceutical composition of the present invention can prevent, improve, or treat symptoms or diseases selected from the group consisting of overeating obesity, diabetes mellitus resulting from overeating obesity, and hepatic fat accumulation resulting from dietary obesity. Furthermore, the present invention provides an appetite suppressant or postprandial satiety-sustaining agent having a novel mechanism of action, in which, when D-allose is included as an active ingredient, the appetite suppressant effect or postprandial satiety-sustaining effect is not reduced by GLP-1 receptor antagonism. [Brief explanation of the drawing]

[0009] [Figure 1] The graph shows the portal vein activity of GLP-1 measured in mice after administration of either test monosaccharides or physiological saline, respectively. Different letters indicate a statistically significant difference of p<0.05 (ANOVA and Tukey's test). [Figure 2] The following shows the amount of standard powdered feed consumed by each mouse after administration of each test monosaccharide. *p<0.05, **p<0.01 (ANOVA and Tukey test). [Figure 3] This is a figure showing the relative values obtained by normalizing the results of Fig. 2 with respect to the physiological saline group at each time point on each experimental day. †p < 0.05, ††p < 0.01 (Dunn's test after Kruskal-Wallis test, vs. physiological saline), *p < 0.05, **p < 0.01 (Mann-Whitney test) [Figure 4] It shows the food intake of standard powdered feed in each mouse that was pre-administered with a GLP-1 receptor antagonist and then administered with a test monosaccharide.

Mode for Carrying Out the Invention

[0010] 1. D-allose, D-sorbose or derivatives thereof Commercially available products may be used for D-allose and D-sorbose, or they may be obtained by production by enzymes (such as keto - 3-epimerase, L-rhamnose isomerase, D-tagatose-3-epimerase, etc.) from saccharides (including sugar alcohols, etc.), or by chemical methods (such as alkali isomerization, etc.), chemical synthesis, or isolation from natural products.​​​​​​​​​​​​​​​The polymers in which two or more D-allose molecules or two or more D-sorbose molecules are polymerized in (i) are not particularly limited as long as the constituent units mainly consist of D-allose or D-sorbose, respectively, but polymers consisting only of D-allose or only of D-sorbose are more preferred.

[0013] Specific examples of D-allose sugar adducts of (ii) include, for example, monoglucosyl-α-D-allose, α-maltosyl-α-D-allose, α-maltotriosyl-α-D-allose, and α-maltotetraosyl-α-D-allose. Specific examples of D-sorbose sugar adducts of (ii) include, for example, monoglucosyl-α-D-sorbose, α-maltosyl-α-D-sorbose, α-maltotriosyl-α-D-sorbose, and α-maltotetraosyl-α-D-sorbose.

[0014] 2. Appetite suppressants, post-meal satiety-prolonging agents, GLP-1 secretion promoters The appetite suppressant of the present invention contains D-allose, D-sorbose, or derivatives thereof as active ingredients and exhibits an appetite-suppressing effect. The appetite-suppressing effect refers to the effect of reducing the amount of food consumed in a single meal or reducing the number of meals consumed per day compared to before taking the appetite suppressant of the present invention. Furthermore, the postprandial satiety-sustaining agent of the present invention contains D-allose, D-sorbose, or derivatives thereof as active ingredients and exhibits a postprandial satiety-sustaining effect. Postprandial satiety is generally obtained by the stimulation of the vagus nerve due to the expansion of the stomach wall and the rise in blood glucose levels due to food intake. In the present invention, the postprandial satiety-sustaining effect is the effect of D-allose, D-sorbose, or derivatives thereof in sustaining the feeling of satiety obtained after a meal. Similar to the appetite-suppressing effect, it is an effect in which the amount of food consumed in one meal decreases or the number of meals consumed in a day decreases compared to before taking the postprandial satiety-sustaining agent of the present invention. Note that the decrease in food intake can be expressed as a decrease in the energy intake of the food consumed.

[0015] In the present invention, the use of appetite suppression or sustained satiety includes the use of suppressing hunger, improving satiety, and preventing overeating.

[0016] GLP-1 is a hormone secreted from L cells in the intestines after a meal, and has been reported to have appetite-suppressing and glucose-tolerant effects (Non-Patent Literature 4). Because GLP-1 is broken down by DPP-4 immediately after secretion, it is an unstable gastrointestinal hormone in the body and is known to act on the central nervous system via GLP-1 receptors expressed on afferent vagus nerves. The inventors previously reported that D-allulose selectively promotes the secretion of only GLP-1 among the major gastrointestinal hormones and exerts an appetite-suppressing effect via afferent vagus nerves (Non-Patent Literature 5).

[0017] D-allose or its derivatives, which are the active ingredients of the appetite suppressant and postprandial satiety-sustaining agent of the present invention, did not exhibit a GLP-1 secretion-promoting effect, but did exhibit an appetite suppressant effect. No appetite suppressant effect has been reported for D-allose to date. Furthermore, D-allose or its derivatives are not affected by pre-administration of GLP-1 receptor inhibitors. That is, the appetite suppressant effect or postprandial satiety-sustaining effect is not reduced by GLP-1 receptor antagonism. From this, it is considered that the appetite suppressant effect and postprandial satiety-sustaining effect of D-allose or its derivatives are not mediated through the GLP-1 receptor. Considering that D-allose selectively promotes the secretion of only GLP-1 among the major gastrointestinal hormones and exerts an appetite-suppressing effect via the afferent vagus nerve, the fact that D-allose did not exhibit a GLP-1 secretion-promoting effect, and furthermore, that it exhibited an appetite suppressant effect and a postprandial satiety-sustaining effect despite not exhibiting a GLP-1 secretion-promoting effect, could not have been predicted from prior art.

[0018] Because D-allose or its derivatives exhibit a mechanism of action that does not involve the promotion of GLP-1 secretion through action on the intestines, it is possible that they are taken up by the brain and directly act on the brain's satiety and hunger centers to reduce appetite. Furthermore, since D-allose may exert its effects even without going through the gastrointestinal tract, it may be possible to use it not only orally but also as an intravenous or injectable drug. Furthermore, even under conditions where GLP-1 is affected by blood glucose and other factors, D-allose can directly act on the central nervous system through a GLP-1-independent mechanism to suppress appetite. Moreover, because it has a different mechanism of action than GLP-1, D-allose or its derivatives may be effective for patients who are resistant to intestinal GLP-1 or GLP-1 receptor agonists. It may also help avoid enhanced appetite suppression and serious side effects that can occur when used in combination with GLP-1 agonists.

[0019] D-sorbose or its derivatives, which are the active ingredients of the appetite suppressant and postprandial satiety-sustaining agent of the present invention, have been found to promote GLP-1 secretion and induce an appetite-suppressing effect. Furthermore, D-sorbose or its derivatives are affected by pre-administration of a GLP-1 receptor inhibitor, and their appetite-suppressing effect or postprandial satiety-sustaining effect is reduced. From this, it is thought that D-sorbose or its derivatives, like D-allulose, promote GLP-1 secretion and exert an appetite-suppressing effect via the afferent vagus nerve. D-sorbose or its derivatives can be used as an active ingredient in GLP-1 secretion promoters.

[0020] <Pharmaceutical composition> The pharmaceutical composition of the present invention contains D-allose, D-sorbose, or derivatives thereof as an active ingredient. The pharmaceutical composition of the present invention may also contain the appetite suppressant, postprandial satiety-sustaining agent, or GLP-1 secretion-promoting agent of the present invention described above. The pharmaceutical composition of the present invention is preferably for oral administration. It may contain any carrier or component that can be used in an oral formulation. For pharmaceutical applications, this includes the prevention, improvement, or treatment of symptoms or diseases selected from the group consisting of obesity caused by overeating, and diabetes and hepatic fat accumulation resulting from obesity.

[0021] <Food Composition> The food composition of the present invention contains D-allose, D-sorbose, or derivatives thereof as an active ingredient. The food composition of the present invention may also contain the appetite suppressant, postprandial satiety-sustaining agent, or GLP-1 secretion-promoting agent of the present invention described above. The food composition of the present invention is a food for use selected from the group consisting of appetite suppression or prolonged satiety after meals, prevention or improvement of obesity caused by overeating, prevention or suppression of elevated blood glucose levels caused by obesity caused by overeating, and prevention or suppression of hepatic fat accumulation caused by obesity. These foods include Foods for Specified Health Uses and Foods with Function Claims. The types of food in the food composition of the present invention are not particularly limited, but include: non-alcoholic beverages such as coffee, sports drinks, dairy beverages (beverages containing dairy components, soy milk, rice milk, almond milk, coconut milk, etc.), non-alcoholic beer-flavored beverages, juices, tea beverages (including black tea (milk tea, lemon tea, etc.), oolong tea, green tea, matcha, hojicha, genmaicha, barley tea, rooibos tea, mate tea, eucommia tea, black bean tea, etc.); alcoholic beverages such as beer, beer-flavored alcoholic beverages (low-malt beer, third-category beer, etc.), chuhai, sours, cocktails, and highballs; dairy-containing products such as pudding, custard cream, yogurt, cream, cheese, butter, mousse, and condensed milk; Japanese sweets such as bean paste, yokan, dorayaki, mizuyokan, manju, monaka, shiruko, dango, mochi, bean paste, and uiro; fruit preparations and fruits Examples include: sauces, jelly and other water-based sweets, biscuits, cookies, bread, crackers, pretzels, steamed buns, cakes, steamed cakes, donuts, muffins, sponge cakes, castella, canelés, pies, choux pastries, waffles, macarons, pizza, pancakes and other bakery products; meringue; noodles such as Chinese noodles, udon, soba, somen, hiyamugi, pasta (spaghetti, macaroni, etc.), cold noodles, pho, rice vermicelli, and glass noodles; rice crackers such as senbei, arare, and okaki; frozen desserts such as ice cream, ice milk, lacto ice, and frozen desserts; dipping sauces and condiments; seasonings such as sushi vinegar, dressings, mayonnaise, ketchup, and sauces; cooked foods such as curry, stew, pasta, fried rice, pilaf, croquettes, shumai, dumplings, steamed buns, tempura and fried foods, takoyaki, and okonomiyaki; tofu products; flour paste; batter; high-calorie liquid diets; and enteral nutrition formulas.

[0022] The daily intake or dosage of the pharmaceutical composition or food composition may be, for example, 0.001 to 100 g, 0.1 to 50 g, 0.5 to 20 g, or 1 to 10 g, as the total amount of the active ingredients D-allose and D-sorbose.

[0023] The daily intake or dosage of the pharmaceutical composition or food composition may be, for example, 1 mg / kg body weight or more, 10 mg / kg body weight or more, or 100 mg / kg body weight or more, and 1 g / kg body weight or less, or 0.1 g / kg body weight or less, as the total amount of the active ingredients D-allose and D-sorbose.

[0024] In this specification, the amount of D-allose or D-sorbose in a derivative of D-allose or D-sorbose is expressed as the amount of D-allose moiety or D-sorbose moiety. [Examples]

[0025] <Material> D-glucose and D-fructose were purchased from Fujifilm Wako Pure Chemical Corporation (Osaka, Japan). The other four rare sugars, D-allose, D-allulose, D-tagatose, and D-sorbose, were supplied by Matsutani Chemical Industry Co., Ltd. (Itami, Japan), with a purity of over 98%. All monosaccharides were dissolved in distilled water for administration to mice. The GLP-1 receptor antagonist Exendin(9-39) (hereinafter, Ex(9-39)) was custom synthesized by GenScript Japan (Tokyo, Japan) and was of Guaranteed Reagent (GR) grade. All other chemicals were of GR grade or higher.

[0026] <Animal> Male C57BL / 6J mice were purchased from Jackson Laboratory Japan Co., Ltd. (Yokohama, Japan) and raised in an environment with controlled temperature (22.5±2℃), humidity (55%±10%), and lighting (light period; 7:30-19:30). The purchased mice were allowed to acclimate to the new environment for at least one week prior to the experiments. Standard feed (CE-2, CREA Japan, Tokyo, Japan) and water were freely available. All experiments used male mice aged 8-20 weeks. The animal experiments were approved by the Animal Experiment Committee of Kyoto Prefectural University and conducted in accordance with the regulations concerning animal experiments (Approval numbers: KPU030402-C, KPU060327-RC-5).

[0027] <Statistical analysis> All data are presented as mean ± SEM. Statistical analysis was performed using one-way analysis of variance (ANOVA), Kruskal-Wallis test, or Mann-Whitney U test. If a significant difference was found between groups using ANOVA, a post-hoc comparison was performed using Tukey's test or Dunn's test. For relative value analysis, non-parametric tests such as the Kruskal-Wallis test and Mann-Whitney U test were used. All statistical analyses were performed using Prism 10 (GraphPad Software, San Diego, CA, USA), with p<0.05 considered significant.

[0028] Experiment A: Measurement of portal vein GLP-1 concentration Mice were fasted overnight (from 18:00 to 10:00 the following day). Six monosaccharide solutions (1g / 10ml / kg or 3g / 10ml / kg) or physiological saline were administered orally (po) using a stainless steel tube. One hour after administration, blood was collected from the portal vein under isoflurane anesthesia. The blood collection syringe contained heparin (final concentration 50 IU / ml), aprotinin (final concentration 500 KIU / ml), and the DPP-IV inhibitor vildagliptin (final concentration 10 μM). After centrifugation (4,000 rpm, 4°C for 10 minutes), plasma was obtained and stored at -80°C until measurement. Active GLP-1 levels were measured using an active GLP-1 ELISA kit (EGLP-35K; Millipore, MA, USA).

[0029] Experiment B: Measurement of food intake The mice were housed in individual cages and allowed to become accustomed to a standard powdered diet (CE-2, 3.4 kcal / g, CREA Japan) for at least one week, and were thoroughly accustomed to the feeding trough (SN-950, Shinano Seisakusho, Tokyo, Japan) and handling. The mice were fasted for 16 hours from 18:00 the day before the experiment, and water was provided freely. At 9:50 the following day, they were orally administered a monosaccharide solution (1 or 3 g / 10 ml / kg) or physiological saline (10 ml / kg), and given the CE-2 powdered diet at 10:00. The weight of the feeding trough containing the powdered diet and the spilled diet was measured at 1 hour, 3 hours, 6 hours, and 24 hours later. The cumulative energy intake of ingested food (CE-2; 3.4 kcal / g) and administered monosaccharides (D-glucose and D-fructose; 4 kcal / g, D-tagatose; 2 kcal / g, D-sorbose; 1 kcal / g, D-allose and D-allulose; 0 kcal / g) was expressed at each time point. To investigate the involvement of GLP-1R signaling, Ex(9-39) 600 nmol / 5 ml / kg or physiological saline (5 ml / kg) was administered once by injection (intraperitoneal administration, ip) 15 minutes prior to oral administration. This GLP-1 receptor inhibitor dosage is based on previous studies showing that Ex(9-39) 600 nmol / kg inhibits the appetite-suppressing effect of D-allulose (PMID: 29317623).

[0030] In the following examples, Sal represents the group administered physiological saline, Glu represents D-glucose, Allo represents D-allose, Fru represents D-fructose, Allu represents D-allulose, Tag represents D-tagatose, and Sol represents D-sorbose. The measured values ​​for each individual mouse are indicated by circles on the graph.

[0031] <Result> 1. Changes in plasma GLP-1 concentration after a single oral administration. Experiment A yielded the following results. When four types of ketohexoses (D-fructose, D-allulose, D-tagatose, and D-sorbose) were administered at a dose of 1 g / kg, the concentration of active GLP-1 in the portal vein increased significantly by approximately 3 to 4 times compared to physiological saline (physiological saline: 9.22 ± 1.02 pM vs. D-fructose: 37.6 ± 7.20 pM, D-allulose: 35.8 ± 5.52 pM, D-tagatose: 44.1 ± 4.09 pM, D-sorbose: 31.6 ± 4.65 pM, Figure 1A). At high doses of 3 g / kg, these ketohexoses further increased plasma GLP-1 concentrations by approximately 4-6 times compared to physiological saline (physiological saline: 15.2 ± 1.75 pM vs. D-fructose: 66.72 ± 8.40 pM, D-allulose: 92.1 ± 10.7 pM, D-tagatose: 75.0 ± 9.82 pM, D-sorbose: 94.8 ± 9.83 pM, Figure 1B). No significant difference was observed in the GLP-1 secretion-promoting effect of the four ketohexoses at each dosage (Figures 1A and B). On the other hand, the two aldohexoses (D-glucose and D-allose) did not significantly increase plasma GLP-1 concentrations at either 1 g / kg or 3 g / kg (Figures 1A and B). These results indicate that ketohexoses containing rare sugars, rather than aldohexoses, dose-dependently increase GLP-1 concentrations in mice.

[0032] 2. Suppression of food intake by oral administration Experiment B yielded the following results. The effects of two types of aldohexoses and four types of ketohexoses on feeding behavior were investigated. Mice fasted overnight were orally administered monosaccharides immediately before refeeding, and food intake was measured 1, 3, 6, and 24 hours after administration. Figure 2 shows the absolute values ​​(cumulative food intake, kcal) of food intake in each monosaccharide experiment, while Figure 3 shows the relative values ​​(relative cumulative food intake, %) normalized to the saline group at each time point on each experimental day. Single doses of D-glucose at 1 g / kg and 3 g / kg did not change food intake at any time point (Figures 2 and 3). Unexpectedly, D-allose did not significantly increase GLP-1 secretion, but particularly at 3 g / kg, it significantly reduced food intake 1 to 6 hours after administration (Figures 2 and 3). Four ketohexoses (D-fructose, D-allulose, D-tagatose, and D-sorbose) significantly stimulated GLP-1 secretion at 1 and 3 g / kg and reduced food intake in a dose-dependent manner (Figures 2C-F and 3). These appetite-suppressing effects were particularly pronounced at the 3 g / kg dose up to 6 hours after administration (Figure 3), but disappeared by 24 hours (data not shown).

[0033] 3. Relationship between GLP-1 receptor antagonism and food intake suppression. To investigate the role of GLP-1 receptor signaling in the food intake suppression effects of the four types of ketohexoses and D-allose described above, mice were pre-administered the GLP-1 receptor antagonist Ex(9-39). More specifically, Ex(9-39) was administered intraperitoneally at a dose of 600 nmol / kg, followed 15 minutes later by oral administration of 1 g / kg of ketohexoses (D-fructose, D-allulose, D-tagatose, D-sorbose), and food intake was measured over time. As shown in Figures 4A-C, pretreatment with Ex9 did not result in a significant decrease in food intake in the four ketohexose groups compared to the saline group at any time point. Furthermore, Figures 4D-F show re-analyzed figures for comparison with Figures 3 and 4A-C. As shown in Figures 4D-F, the Ex9 pretreatment significantly reduced or tended to reduce the appetite-suppressing effect of ketohexoses, particularly at 1 and 3 hours post-administration. These results indicate that the appetite-suppressing effects of the four ketohexoses, including D-fructose, D-allulose, D-tagatose, and D-sorbose, are mediated by GLP-1 receptor signaling. In contrast, similar Ex9 pretreatment did not reduce the food intake-suppressing effect of 3 g / kg D-allose, particularly at 3 and 6 hours post-administration (Figures 4A-C). Furthermore, no significant difference in food intake was observed between the D-allose administration groups, regardless of whether or not Ex9 pretreatment was performed (Figures 4D-F). Therefore, the food intake-suppressing effect of D-allose is thought to be mediated by a mechanism independent of GLP-1 receptor signaling.

Claims

1. An appetite suppressant or a post-meal satiety-prolonging agent containing D-allose, D-sorbose, or derivatives thereof as an active ingredient.

2. An appetite suppressant or postprandial satiety-sustaining agent according to claim 1, comprising D-allose or a derivative thereof as an active ingredient, wherein the appetite suppressant effect or postprandial satiety-sustaining effect is not reduced by GLP-1 receptor antagonism.

3. An appetite suppressant or postprandial satiety-sustaining agent according to claim 1, comprising D-sorbose or a derivative thereof as an active ingredient, wherein the appetite suppressant effect or postprandial satiety-sustaining effect is reduced by GLP-1 receptor antagonism.

4. A GLP-1 secretion promoter containing D-sorbose or a derivative thereof as an active ingredient.

5. A pharmaceutical composition comprising D-allose, D-sorbose, or derivatives thereof as an active ingredient, for the prevention, improvement, or treatment of symptoms or diseases selected from the group consisting of obesity due to overeating, diabetes mellitus resulting from obesity due to overeating, and hepatic fat accumulation resulting from obesity due to overeating.

6. A food composition comprising D-allose, D-sorbose, or derivatives thereof as an active ingredient, for uses selected from the group consisting of appetite suppression, sustained satiety, prevention or improvement of obesity caused by overeating, prevention or suppression of elevated blood glucose levels due to obesity caused by overeating, and prevention or suppression of hepatic fat accumulation caused by obesity.

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