JP2015189747A - Inhibitors of diacylglycerol acyltransferase and inhibitors of fatty liver - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide inhibitors of diacylglycerol acyltransferase and inhibitors of fatty liver.SOLUTION: An inhibitor of diacylglycerol acyltransferase of the invention comprises, as the effective component, an oligosaccharide comprised of linked 1-10 molecules of monosaccharides, mainly of mannose, and inhibits expression of one or more diacylglycerol acyltransferases selected from the group consisting of DGAT1 and DGAT2. Also provided is an inhibitor of fatty liver, of which effective component is an oligosaccharide comprised of linked 1-10 molecules of monosaccharides, mainly of mannose.

Description

  The present invention relates to a diacylglycerol acyltransferase inhibitor and a fatty liver inhibitor composed of oligosaccharides containing mannose as a constituent sugar.

  Fatty liver is a condition in which neutral fat accumulates in the liver cells more than necessary. In recent years, along with the westernization of eating habits, fatty liver has also increased rapidly. In particular, fatty liver with obesity is a problem because it increases the risk of lifestyle diseases such as dyslipidemia, hypertension and diabetes. Even when the cause of fatty liver is thought to be other than excessive intake of alcohol, liver dysfunction has progressed, leading to cirrhosis and liver cancer. For this reason, the importance of the treatment and prevention of fatty liver has been widely recognized.

  On the other hand, the physiological functions of β-1,4-mannooligosaccharides such as β-1,4 mannobiose, which is a compound in which D-mannose is bonded to β-1,4, have attracted attention. In addition, an important partial structure of a sugar chain of human glycoprotein includes mannooligosaccharide in which D-mannose is linked by β-1,4, and it can be applied not only as a raw material for foods but also as a raw material for pharmaceuticals. Expected. For example, it has been reported that the amount of total cholesterol and neutral fat in serum decreases by ingesting oligosaccharides containing mannose as a constituent sugar (see, for example, Patent Document 1).

JP 2006-169256 A

  Patent Document 1 discloses that oligosaccharides containing mannose as a constituent sugar can reduce the amount of serum lipids, but does not describe any effect on fat that has already been accumulated in the liver. Although it can be expected that the amount of fat accumulated in the liver will be reduced in the future by reducing the amount of lipid in the serum, it is difficult to treat fatty liver alone.

  An object of this invention is to provide the inhibitor with respect to diacylglycerol acyltransferase (DGAT), and the fatty liver inhibitor. DGAT is an enzyme involved in triglyceride synthesis, and suppressing the action of DGAT in the liver is effective in preventing and improving fatty liver.

  As a result of diligent research to solve the above-mentioned problems, the present inventors have found that an oligosaccharide in which 1 to 10 molecules of saccharides mainly composed of mannose are bonded has a DGAT-inhibiting action, and the oligosaccharide is taken orally. As a result, it was found that the amount of accumulated fat in the liver can be reduced, and the present invention has been completed.

[1] The DGAT inhibitor according to the first aspect of the present invention is one type selected from the group consisting of DGAT1 and DGAT2, comprising as an active ingredient an oligosaccharide in which 1 to 10 molecules of monosaccharides mainly composed of mannose are bound. It is characterized by suppressing the above DGAT expression.
[2] In the DGAT inhibitor of [1], the oligosaccharide is one in which 1 to 10 molecules of one or more monosaccharides selected from the group consisting of mannose, glucose, galactose and fructose are bonded. Is preferred.
[3] In the DGAT inhibitor of [1] or [2], the ratio of the mannose residue in the oligosaccharide is preferably 70% by mass or more.
[4] In the DGAT inhibitor according to any one of [1] to [3], the oligosaccharide is preferably obtained by hydrolyzing mannan.
[5] In the DGAT inhibitor of [4], it is preferable that the mannan is obtained from coffee beans and / or coffee extraction residues.
[6] In the DGAT inhibitor of [1], the oligosaccharide is preferably an oligosaccharide having 1 to 10 molecules of mannose bonded thereto.
[7] In the DGAT inhibitor of [1], the oligosaccharide is preferably a β-1,4-mannooligosaccharide having 1 to 10 molecules of mannose bonded thereto.
[8] In the DGAT inhibitor of any one of [1] to [7], the content ratio of the oligosaccharide is preferably 60% by mass or more based on the total solid content.
[9] The DGAT inhibitor of any one of [1] to [8] is preferably taken for the treatment or prevention of fatty liver.
[10] The fatty liver inhibitor according to the second aspect of the present invention is characterized in that an active ingredient is an oligosaccharide in which 1 to 10 molecules of monosaccharide mainly composed of mannose are bonded.

  Since the DGAT inhibitor according to the present invention has an action of suppressing the expression of DGAT1 and DGAT2 involved in triglyceride synthesis in the liver, the amount of neutral fat accumulated in the liver by ingesting the DGAT inhibitor Can be effectively reduced. That is, the DGAT inhibitor according to the present invention is particularly preferably used for the treatment and prevention of fatty liver.

In Example 1, it is the figure which showed the measurement result (average value) of the amount of triglycerides in a liver in the test feed group which administered the test feed which mix | blended manno-oligosaccharide, and the control feed group which administered the control feed. In Example 1, it is the figure which showed the relative expression level which made the expression level of the control feed group 1 about the expression level of DGAT1 and DGAT2 of a test feed group and a control feed group. In Example 2, it is the figure which showed the result of the liver CT value (average value of 4 persons) before and after taking a test drink. In Example 2, it is the figure which showed the result of the [liver CT value] / [spleen CT value] value (average value of 4 persons) before and after intake of the test beverage.

  In the present invention and the specification of the present application, “an oligosaccharide mainly composed of mannose” means an oligosaccharide mainly composed of mannose which is a monosaccharide. Here, the term “oligosaccharide” generally refers to a substance that is located between a monosaccharide and a polysaccharide and consists of a glycosyl bond of a certain small number of monosaccharide molecules. That is, it is a polymer with a relatively small number of monosaccharides bound thereto. The term “oligosaccharide“ class ”” means a composition containing a plurality of oligosaccharides having different types and numbers of constituent monosaccharides. The term “oligosaccharide“ s ”” mainly composed of mannose refers to a composition in which the ratio of mannose to the constituent monosaccharides of the entire composition is 50% or more among oligosaccharides. In the present invention and the present specification, the term “mannooligosaccharide” is used in the same meaning as the term “oligosaccharide mainly composed of mannose”.

  In the present invention and the present specification, “DP” may be used to indicate the degree of polymerization of the oligosaccharide. DP means the number of monosaccharides constituting the oligosaccharide. That is, mannose, which is a monosaccharide, is expressed as “DP1”, and a mannooligosaccharide composed of four mannoses is expressed as a degree of polymerization of 4, that is, “DP4”. From an academic point of view, sugars with a degree of polymerization of 1 (DP1) are monosaccharides, not oligosaccharides. However, since the oligosaccharide (composition) used in the present invention may contain a monosaccharide, in this specification, even in such a case, the term “oligosaccharide” is collectively referred to. To do. That is, in the case of “an oligosaccharide mainly composed of mannose having 1 to 10 molecules bonded with mannose-based monosaccharides”, this saccharide composition also includes monosaccharides having a degree of polymerization of 1. Please understand that there are cases.

  The DGAT inhibitor according to the present invention is an oligosaccharide in which 1 to 10 molecules of monosaccharides mainly composed of mannose are bonded, that is, among the “oligosaccharides mainly composed of mannose”, the number of constituent monosaccharides is 1 to 10 molecules. Is a composition. The active ingredient of the DGAT inhibitor according to the present invention includes a plurality of types of oligosaccharides in which 1 to 10 molecules of one or more monosaccharides selected from the group consisting of mannose, glucose, galactose and fructose are bonded. And an oligosaccharide (composition) in which the proportion of mannose in the whole constituent monosaccharide is 50% or more is preferable, and at least one monosaccharide selected from the group consisting of mannose and fructose as the constituent monosaccharide is More preferred are oligosaccharides (compositions) containing a plurality of types of oligosaccharides having 1 to 10 molecules bonded, and having a mannose ratio of 50% or more of the total constituent monosaccharides.

  The active ingredient of the DGAT inhibitor according to the present invention is preferably an oligosaccharide (composition) in which the ratio of mannose residues in the oligosaccharide (the ratio of mannose in the total constituent monosaccharides) is 70% by mass or more. More preferred is an oligosaccharide (composition) in which the ratio of mannose residues in the saccharide is 80% by mass or more. When the ratio of mannose residues is sufficiently high, the DGAT inhibitory action by mannooligosaccharides can be obtained more effectively, and the content of other monosaccharides such as glucose is relatively low, so Can be kept low, making it easy to apply widely to foods and drinks, supplements, pharmaceuticals, and the like.

  As an “oligosaccharide mainly composed of mannose” used as an active ingredient of the DGAT inhibitor according to the present invention, since the bitter taste derived from monosaccharide mannose can be suppressed, the free mannose content is suppressed to 50% by mass or less. Are preferred. The “oligosaccharide mainly composed of mannose” is preferably one having a high content of oligosaccharides bound with 2 to 9 molecules of monosaccharides, and has a content of oligosaccharides bound with 2 to 6 molecules of monosaccharides. Many are more preferable. In addition, the “oligosaccharide mainly composed of mannose” is preferably such that the content ratio of oligosaccharides in which each constituent monosaccharide is β-1,4-bonded is 50% by mass or more.

  The “oligosaccharide mainly composed of mannose” used in the present invention is a mannooligosaccharide composed of only mannose (only mannose is a structural unit), that is, an oligosaccharide in which 1 to 10 molecules of mannose are bonded. It is also preferable that there is. In this case, β-1,4-mannooligosaccharide having 1 to 10 molecules of mannose bonded thereto is more preferable.

  As the “oligosaccharide mainly composed of mannose” used in the present invention, those obtained by hydrolyzing mannan are preferable. In addition, in this invention and this-application specification, when only calling it "mannan", in addition to mannan which is a polysaccharide which only has D-mannose as a structural unit, galactomannan which is a polysaccharide which has mannose and galactose or glucose and a structural unit, Glucomannan shall be included in a broad sense. D-mannose is an aldohexose in which the configuration of the hydroxyl group bonded to the carbon adjacent to the carboxyl group in D-glucose is reversed.

  Here, the raw material mannan can be obtained by extraction from, for example, copra meal obtained from coconut coconut, fuchs, South African coconut plants Huacra Palm, tsukuneimo mannan, and yam mannan. Mannan thus obtained is treated by one or more methods selected from acid hydrolysis, high-temperature heat hydrolysis, enzyme hydrolysis, and microbial fermentation, preferably activated carbon treatment, adsorption resin treatment, A sugar mixture can be obtained by purification by an ion exchange resin treatment, an ion exchange membrane treatment or the like. This mixture contains the above-described “oligosaccharides mainly composed of mannose”. Therefore, the composition thus obtained is used as an active ingredient of the DGAT inhibitor according to the present invention. Furthermore, “oligosaccharides mainly composed of mannose” include glucomannan, locust bean gum, guar gum, etc. contained in cornflower, lily, daffodil, ganbana, etc., acid hydrolysis, high temperature heating hydrolysis, enzyme Treated by one or more methods selected from hydrolysis and microbial fermentation, separated and purified by activated carbon treatment, adsorption resin treatment, ion exchange resin treatment, ion exchange membrane treatment, etc., and mannose as a constituent sugar It may be produced by increasing the ratio.

  The “oligosaccharide mainly composed of mannose” used in the present invention is one kind selected from raw coffee beans or roasted coffee beans from acid hydrolysis, high-temperature heat hydrolysis, enzyme hydrolysis, and microbial fermentation. Or it can obtain by processing by 2 or more types of methods, and refine | purifying by methods, such as activated carbon processing, adsorption resin processing, ion-exchange resin processing, and ion-exchange membrane processing. Alternatively, the used coffee residue is treated by one or more methods selected from acid hydrolysis, high-temperature heat hydrolysis, enzyme hydrolysis, and microbial fermentation, and activated carbon treatment, adsorption resin treatment, ion exchange resin It can also be obtained by purification by a method such as treatment or ion exchange membrane treatment. In general, when roasted and ground coffee is extracted with a commercial extractor, galactose, which is a side chain of galactomannan contained in roasted coffee, is solubilized or arabinogalactan is solubilized by hydrolysis. . Therefore, it is presumed that the coffee residue is rich in mannan and has a linear structure. On the other hand, although cellulose is hardly decomposed and remains as a residue, an oligosaccharide mainly composed of mannose can be obtained by appropriately selecting conditions for specifically hydrolyzing mannan without decomposing cellulose.

  Particularly, the method for decomposing the coffee extraction residue includes, but is not limited to, a method of hydrolyzing with an acid and / or high temperature, a method of decomposing with an enzyme, and a method of decomposing by microbial fermentation. Methods for hydrolyzing with an acid and / or high temperature are disclosed in JP-A-61-96947, JP-A-2-200147, and the like. It is possible to hydrolyze spent coffee residue that comes out in a commercial coffee multistage extraction system by adding an acid catalyst in a reaction vessel and treating it at a high temperature for a short time without adding an acid catalyst. Can also be obtained. The method using a tubular plug flow reactor is convenient, but good results can be obtained using any reactor that is suitable for a method in which a reaction is performed at a relatively high temperature for a short time. It is done. Mannanoligosaccharides of DP10-40 are decomposed into DP1-10 manno-oligosaccharides by adjusting the reaction time and reaction temperature, solubilizing and hydrolyzing, and then separating from the coffee residue to obtain manno-oligosaccharides. Here, the coffee extraction residue means a so-called coffee extraction cake after the roasted and ground coffee is extracted with a solvent such as water in the air or under pressure.

  Used as “oligosaccharides mainly composed of mannose” when coffee beans (including roasted coffee beans and roasted and ground coffee beans) and / or those obtained by hydrolysis treatment of coffee extraction residue are used. There are no particular restrictions on the type and production area of the coffee beans, and any coffee bean such as Arabica, Robusta, and Riberica can be used, and coffee beans from any origin such as Brazil and Colombia can be used. Only beans may be used alone, or two or more kinds of blended beans may be used. Usually, even low-quality coffee beans or small-sized coffee beans that are discarded as having no commercial value can be used. Coffee beans roasted in a shallow roast, shallow roast, medium roast, deep roast by a roasting machine (direct fire, hot air, far red, charcoal fire type, etc.) generally used for the above coffee beans, and this roast Roasted and ground coffee (coarse ground, medium ground, medium ground, medium ground, fine ground, etc.) Can also be used.

  In addition, as the coffee extraction residue, after the roasted and ground coffee is extracted in a normal liquid coffee or instant coffee manufacturing process, it may be extracted under normal pressure or under pressure, and any origin and production method may be used. Even coffee extraction residues can be used.

Here, some of the hydrolysis treatments will be described in detail. As a method of decomposing with an enzyme, for example, a coffee extraction residue may be suspended in an aqueous medium, and commercially available cellulase, hemicellulase, etc. may be added thereto and suspended with stirring. There are no particular problems with the amount of enzyme, the temperature at which it acts, and other conditions as long as it is the amount, temperature, and conditions used in normal enzyme reactions, depending on the optimum amount of enzyme used, temperature, conditions and other factors. What is necessary is just to select suitably.
As a method for decomposing by microbial fermentation, for example, a microorganism that produces cellulase, hemicellulase, etc. may be inoculated and cultured in a coffee extraction residue suspended in an aqueous medium. The microorganism to be used may be any microorganism that produces an enzyme that decomposes mannan in the coffee extraction residue such as bacteria and basidiomycetes, and the culture conditions and the like may be appropriately selected depending on the microorganism to be used.

  The reaction solution containing “oligosaccharides mainly composed of mannose” obtained by the above method can be purified as necessary. As purification methods, bone charcoal, activated carbon, carbonic acid saturation method, adsorption resin, magnesia method, solvent extraction method, etc. are used for decolorization and deodorization, and ion exchange resin, ion exchange membrane, electrodialysis, etc. are used for desalting and deoxidation. Can be mentioned. The combination of the purification methods and the purification conditions may be appropriately selected according to the amount of pigment, salt, acid, etc. in the reaction solution containing the oligosaccharide mainly composed of mannose and other factors.

  “Oligosaccharides mainly composed of mannose” used in the present invention are subjected to purification treatment such as decolorization, deodorization, deoxidation, etc. with activated carbon, ion exchange resin, solvent, etc. as necessary before being used as active ingredients. You may keep it.

  The DGAT inhibitor according to the present invention contains the “oligosaccharide mainly composed of mannose” as an active ingredient. The “oligosaccharide mainly composed of mannose” has an action of suppressing the expression of DGAT1 and DGAT2 involved in the synthesis of neutral fat in the liver. Therefore, the DGAT inhibitor according to the present invention containing the “oligosaccharide mainly composed of mannose” as an active ingredient has an effect of reducing the amount of fat accumulated in the liver, and treatment and prevention of fatty liver. Is particularly preferably used.

  The DGAT inhibitor according to the present invention may consist only of the “oligosaccharide mainly composed of mannose” or may contain other components. The content of the “oligosaccharide mainly composed of mannose” in the DGAT inhibitor according to the present invention is preferably 60% by mass or more, and more preferably 80% by mass or more based on the total solid content.

  The other component may be any as long as it does not impair the DGAT suppressing action of the “oligosaccharide mainly composed of mannose”. For example, excipients, binders, fluidity improvers (anti-caking agents), Various substances used as stabilizers, preservatives, pH adjusters, solubilizers, suspending agents, emulsifiers, thickeners, corrigents, sweeteners, acidulants, fragrances, coloring agents, etc. You may make it contain suitably according to product quality.

  The dosage form of the DGAT inhibitor according to the present invention is not particularly limited, and various dosage forms can be applied. The DGAT inhibitor according to the present invention is preferably suitable for oral administration because it exerts an effect of reducing liver fat mass when taken orally. Examples of the dosage form include tablets, capsules, granules, powders, syrups and the like.

  The DGAT inhibitor according to the present invention contains an oligosaccharide as a main component, and can be orally inoculated very safely. Therefore, the DGAT inhibitor according to the present invention may be blended as a raw material in food and drink as well as as a pharmaceutical product. The effect of improving or preventing fatty liver can be expected by continuously ingesting the food and drink containing the DGAT inhibitor according to the present invention. In addition, it is also preferable to use it as a raw material for feed or cosmetics.

  For example, the “oligosaccharides mainly composed of mannose” prepared by hydrolyzing the coffee extraction residue with acid and / or heat to contain oligosaccharides in high purity as it is or as necessary, activated carbon, ion exchange resin, solvent It can also be used after being subjected to purification treatment such as decolorization, deodorization, deoxidation, etc. and then added to liquid coffee, instant coffee and the like. Here, as liquid coffee, the coffee drink (or what is called a drink containing coffee) put into a can or what is called a PET bottle container and marketed is mentioned. Moreover, as instant coffee, what is called soluble powder coffee which removed the water | moisture content by spraying or freeze-drying the extract which extracted the roasting ground coffee with hot water is mentioned. Examples of the coffee mix beverage include beverages obtained by adding and mixing soluble powdered coffee with sugar, creaming powder, and the like.

  EXAMPLES Next, although an Example is shown and this invention is demonstrated further in detail, this invention is not limited to a following example etc.

[Example 1]
The effects of ingestion of manno-oligosaccharide on the amount of neutral fat in the liver and the expression level of DGAT were examined.

<Preparation of mannooligosaccharide>
A coffee extraction residue having a particle size of about 1 mm after pulverization was prepared as a slurry comprising water and a pulverized product having a total solid concentration of about 14% by mass, and then heat-treated in a 4 m hot plug flow reactor. In the heat treatment, the slurry was pumped to the plug flow reactor with high pressure steam at a rate corresponding to a residence time of 8 minutes and maintained at about 210 ° C. using a 6.35 mmφ orifice. Then, the reaction was stopped rapidly by ejecting the slurry under atmospheric pressure. The resulting slurry was filtered to separate a liquid containing soluble solids from insoluble solids. This soluble solid content-containing liquid is decolorized with activated carbon and then with an adsorption resin, further desalted with an ion exchange resin, concentrated and dried, and thereby an oligosaccharide in which 1 to 10 molecules of monosaccharides mainly composed of mannose are bonded. A composition containing was obtained.

  The polymerization degree (DP) distribution of the composition thus obtained (mannooligosaccharide) was as follows: DP1; 2.4%, DP2; 26.6%, DP3; 20.2%, DP4; 17.8%, DP5; 10.9%, DP6; 8.9%, DP7; 6.0%, DP8; 3.6%, DP9; 1.9%, DP10; 1.7%, and the mannose residue in the sugar chain The group content was 90%. However, the DP distribution and the content of mannose residues in the sugar chain can take various values depending on the hydrolysis conditions. Oligosaccharide DP1 as mannose, DP2 as mannobiose, DP3 as mannotriose, DP4 as mannotetraose, DP5 as mannopentaose, DP6 as mannohexaose, etc. DP7 is mannoheptaose, etc., DP8 is mannooctaose, etc., DP9 is mannononaose, etc., DP10 is mannodekaose, etc., and the binding mode is β-1,4 bond.

<Ingestion to rats>
The obtained mannooligosaccharide was orally administered to rats, and the influence on the amount of fat in the liver and the expression level of DGAT was examined.
SD rats were used for the experiment. After 14 days of preliminary breeding for quarantine and acclimatization period, 16 individuals with no change in body weight and general condition were divided into 2 groups (8 per group) and subjected to the experiment. Animals were housed in controlled environments of temperature, humidity, ventilation rate, and lighting time. The experimental feed was a high-fat feed containing 40% by weight beef tallow as a base (control feed), and a feed prepared by blending mannooligosaccharide prepared above to 1% by weight was used as a test feed. One group of rats had free access to the test diet and the other group of rats had free access to the control diet for 56 days. At the end of the experimental period, the liver was collected.

<Measurement of the amount of neutral fat in the liver>
To about 0.5 g of the collected liver tissue, 4.5 mL of 0.1 M PBS was added and homogenized, and then centrifuged at 3000 rpm for 10 minutes in a cooling centrifuge, and the supernatant was collected. Using the obtained supernatant as a sample, measurement was performed using a commercially available triglyceride measurement kit (manufactured by Wako Pure Chemical Industries, Ltd.).
The measurement results (average value) of the neutral fat in the liver of each group are shown in FIG. It was confirmed that the group to which the test feed containing mannooligosaccharide was administered had less neutral fat in the liver than the group to which the control feed was administered. That is, it is clear that by ingesting mannooligosaccharide, fat accumulated in the liver is reduced and fatty liver is suppressed.

<Measurement of DGAT expression level>
In order to observe the gene expression of the lipid metabolism system in the liver tissue, a section of about 50 mg was prepared immediately after collecting the liver, immediately immersed in RNA later (registered trademark) (manufactured by Funakoshi), and stored at −80 ° C. in a cold storage. . A section of the preserved liver tissue was extracted with total RNA using RNeasy Mini Kit (manufactured by QIAGEN), and then about 100 ng was reverse-transcribed using Quantect Reverse Transfer Kit (manufactured by QIAGEN) to obtain cDNA. Was prepared. Using the obtained cDNA as a template, the expression levels of DGAT1 and DGAT2, which are enzymes related to the triglyceride synthesis system in the liver, were measured using quantitative PCR. Table 1 shows the base sequences of the primers used.

  Regarding the expression levels of DGAT1 and DGAT2 obtained by quantitative PCR, the results of relative expression levels with the expression level of the control feed group being 1 are shown in FIG. It was confirmed that the expression of DGAT1 and DGAT2 was suppressed in the group to which the test diet containing mannooligosaccharide was administered, compared to the group to which the control diet was administered.

[Example 2]
The effect of ingesting the coffee beverage containing the manno-oligosaccharide prepared in Example 1 on fat in the liver was examined.

<Preparation of liquid coffee for human testing>
A test beverage was prepared by mixing the coffee extract, mannooligosaccharide (prepared in Example 1), milk, sugar, high-intensity sweetener and water with the composition shown in Table 2. The test beverage was sterilized according to a conventional method after filling a 275 g bottle can.

<Intake of test beverage and CT value measurement>
The human test was performed on BMI 25 to 30 and 4 adult males whose fatty liver ([liver CT value] / [spleen CT value] value was 0.9 or less) by image diagnosis. Subjects ingested one test drink per day for 12 weeks. Before and after ingestion of the test drink, a CT (Computed tomography) apparatus was used to photograph from the lower right part of the liver to the upper part every 10 mm. CT values were obtained by photographing the liver and spleen under the condition of window level + 20 window width 250 as the Hounsfield unit. Thereafter, the liver CT value and the ratio of the liver CT value to the spleen CT value ([liver CT value] / [spleen CT value]) were compared.

  FIG. 3 shows the results of liver CT values (average values of 4 subjects) before and after the test beverage intake, and FIG. 4 shows the results of [liver CT values] / [spleen CT values] values (average values of 4 subjects). Show. It was confirmed that the CT value in the liver significantly increased after ingestion of the test drink compared to before ingestion. Similarly, it was confirmed that the [liver CT value] / [spleen CT value] value was significantly increased by ingestion of the test beverage compared to before ingestion. From the above results, it was confirmed that the intake of the test beverage containing mannooligosaccharide has an effect of improving fatty liver.

Claims (10)

  It is characterized by suppressing the expression of one or more diacylglycerol acyltransferases selected from the group consisting of DGAT1 and DGAT2, comprising as an active ingredient an oligosaccharide in which 1 to 10 molecules of monosaccharides mainly composed of mannose are bound. A diacylglycerol acyltransferase inhibitor.   2. The diacylglycerol acyltransferase inhibitor according to claim 1, wherein the oligosaccharide is a combination of 1 to 10 molecules of one or more monosaccharides selected from the group consisting of mannose, glucose, galactose and fructose. .   The diacylglycerol acyltransferase inhibitor according to claim 1 or 2, wherein a ratio of mannose residues in the oligosaccharide is 70% by mass or more.   The diacylglycerol acyltransferase inhibitor according to any one of claims 1 to 3, wherein the oligosaccharide is obtained by hydrolyzing mannan.   The diacylglycerol acyltransferase inhibitor according to claim 4, wherein the mannan is obtained from coffee beans and / or a coffee extraction residue.   The diacylglycerol acyltransferase inhibitor according to claim 1, wherein the oligosaccharide is an oligosaccharide having 1 to 10 molecules of mannose bonded thereto.   The diacylglycerol acyltransferase inhibitor according to claim 1, wherein the oligosaccharide is a β-1,4-mannooligosaccharide having 1 to 10 molecules of mannose bonded thereto.   The diacylglycerol acyltransferase inhibitor as described in any one of Claims 1-7 whose content rate of the said oligosaccharide is 60 mass% or more with respect to a total solid.   The diacylglycerol acyltransferase inhibitor according to any one of claims 1 to 8, which is taken for treatment or prevention of fatty liver.   An inhibitor of fatty liver, comprising as an active ingredient an oligosaccharide in which 1 to 10 molecules of monosaccharides mainly composed of mannose are bonded.

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