WO2023063033A1 - サルコペニア肥満抑制組成物、及びこれを含有し糖尿病によって誘導されたサルコペニア肥満を改善するための予防及び／又は治療用組成物 - Google Patents

サルコペニア肥満抑制組成物、及びこれを含有し糖尿病によって誘導されたサルコペニア肥満を改善するための予防及び／又は治療用組成物 Download PDF

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WO2023063033A1
WO2023063033A1 PCT/JP2022/035034 JP2022035034W WO2023063033A1 WO 2023063033 A1 WO2023063033 A1 WO 2023063033A1 JP 2022035034 W JP2022035034 W JP 2022035034W WO 2023063033 A1 WO2023063033 A1 WO 2023063033A1
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composition
mass
obesity
guar gum
sarcopenic
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French (fr)
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真英 濱口
拓郎 岡村
かつら 三浦
裕二 内藤
道明 福井
綾 安部
誠 小関
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太陽化学株式会社
京都府公立大学法人
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Publication of WO2023063033A1 publication Critical patent/WO2023063033A1/ja

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K10/00—Animal feeding-stuffs
    • A23K10/30—Animal feeding-stuffs from material of plant origin, e.g. roots, seeds or hay; from material of fungal origin, e.g. mushrooms
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents

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  • the present invention relates to a composition for suppressing sarcopenia obesity, and a preventive and/or therapeutic composition containing the same for improving sarcopenia induced by diabetes.
  • sarcopenia a phenomenon in which skeletal muscle mass and muscle strength due to aging or disease. This phenomenon is called "sarcopenia”.
  • Sarcopenia is a portmanteau of the Greek words sarco, meaning muscle, and penia, meaning decrease.
  • Sarcopenia reduces resting energy expenditure and physical activity.
  • body fat increases, which induces obesity, resulting in insulin resistance and an increase in tumor necrosis factor. This further promotes sarcopenia, resulting in a negative link between sarcopenia and obesity.
  • sarcopenic obesity which is a combination of sarcopenia and obesity, further increases the risk of lifestyle-related diseases beyond simple "obesity”.
  • the present invention has been made in view of the above problems, and its object is to provide a novel composition for suppressing sarcopenic obesity, and a prophylactic and/or therapeutic composition containing the same for improving sarcopenic obesity induced by diabetes. It is to provide a composition.
  • the present inventor found that a composition containing a specific guar gum hydrolyzate and guar bean protein has sarcopenia obesity inhibitory activity, and basically completed the present invention.
  • the composition for suppressing sarcopenia obesity according to the present invention includes (A) a guar gum decomposition product having an average molecular weight of 1.8 ⁇ 10 3 to 2.0 ⁇ 10 5 and containing 70% by mass or more of those within the average molecular weight range. and (B) guar bean protein, and the viscosity of a 1% by mass aqueous solution when measured with a Brookfield viscometer at 25° C. and 60 rpm is 50 mPa s or less (more preferably 20 mPa s or less).
  • guar gum decomposition product is contained in guar-derived endosperm, and the content ratio of galactose and mannose (galactose:mannose) is in the range of 1:1.5 to 1:2.1. It is obtained by hydrolysis using the derived ⁇ -mannanase to reduce the molecular weight, and has a dietary fiber content of at least 70% by mass and an oligosaccharide content of the guar gum hydrolyzate as determined by the enzyme-HPLC method.
  • amino acids contained in the protein are 15% by mass or less, and among the amino acids contained in the protein (glutamic acid + glutamine + aspartic acid + asparagine) ⁇ 100 mg/100 g, (cystine + tyrosine + serine + threonine) ⁇ 40 mg/100 g, all It is characterized by amino acids ⁇ 150 mg/100 g and a ratio of (A)/(B) of 1000 or less.
  • a composition for preventing and/or treating sarcopenic obesity according to another invention is characterized in that it contains the sarcopenic obesity suppressing composition and is for improving sarcopenic obesity induced by diabetes. .
  • food, drink and feed according to another invention are characterized by containing the composition for suppressing sarcopenia obesity. By ingesting this food and drink, it is possible to improve sarcopenic obesity induced by diabetes, so it is good for diabetic patients.
  • Food and beverages include food and beverages, such as dietary supplements, health foods, foods for specified health uses, foods with function claims, diet therapy foods, general health foods, supplements, tea beverages, coffee beverages, and juices.
  • Feed in the present invention refers to food to be fed to organisms other than humans, and its form is not particularly limited.
  • Organisms to which the feed can be applied are not particularly limited, but examples include farmed animals and pet animals.
  • Farmed animals include livestock such as horses, cattle, pigs, sheep, goats, camels, and llamas, experimental animals such as mice, rats, guinea pigs, and rabbits, and poultry such as chickens, ducks, turkeys, and ostriches. be.
  • Pet animals include, for example, dogs and cats.
  • a novel composition for suppressing sarcopenic obesity and a sarcopenic obesity preventive and/or therapeutic composition containing the same for improving sarcopenic obesity induced by diabetes.
  • FIG. 10 is a graph showing body weight changes over time in Db/Db mice.
  • ⁇ indicates the ND group
  • ⁇ indicates the FFD group
  • ⁇ indicates the PHGG group (same in FIGS. 2 and 4).
  • It is a graph which shows a blood glucose level change after (A) iPGTT test (intraperitoneal glucose tolerance test) and (B) ITT test (insulin tolerance test).
  • FIG. 3 is a graph showing AUC (area under the curve) of blood glucose level graph after (A) iPGTT test and (B) ITT test.
  • “*" indicates p ⁇ 0.05
  • "**” indicates p ⁇ 0.01
  • *** indicates p ⁇ 0.001 (the same applies to other graphs).
  • 2 is a graph showing changes over time in (A) oxygen partial pressure (VO 2 ) and (B) carbon dioxide partial pressure (VCO 2 ).
  • 2 is a graph showing average values of (A) oxygen partial pressure (VO 2 ) and (B) carbon dioxide partial pressure (VCO 2 ) in each group in the light period (Light) and the dark period (Dark).
  • (A) a muscle tissue image of the soleus muscle and (B) a muscle tissue image of the plantar muscle are micrographs.
  • FIG. 1 It is a graph which shows the result of having calculated
  • A Hematoxylin-eosin staining
  • HE Hematoxylin-eosin stain staining
  • C Micrographs of liver tissue taken from each group. be.
  • FIG. 2 is a graph showing the results of examining (A) NAS (non-alcoholic fatty liver disease activity score) and (B) Oil Red O area. Graph showing the results of (A) ALT (alanine aminotransferase), (B) T-Chol (total cholesterol), (C) TG (triglycerides) and (D) NEFA (non-esterified fatty acids) in blood samples. is. 1 is a graph showing the results of examining the concentrations of (A) acetic acid, (B) propanoic acid, and (C) butanoic acid in feces.
  • Fig. 1 is a graph showing the results of examining the concentrations of (A) acetic acid, (B) propionic acid and (C) butyric acid in serum.
  • (F) 1 is a graph showing the results of examining the concentrations of phenylalanine, (G) lysine and (H) glutamic acid.
  • Fig. 2 is a graph showing the results of examination of palmitic acid concentration in (A) feces, (B) serum and (C) muscle.
  • FIG. 3 is a graph showing the results of expression analysis of each gene of (A) tnfa, (B) il6, (C) il1b, (D) cd36 and (E) il22 in the jejunum.
  • FIG. 2 is a graph showing the expression analysis results of (A) trim63, (B) fbxo32, (C) tnfa, (D) il6, (E) foxo1 and (F) hdac4 genes in muscle.
  • As inflammation-related cells in the small intestine (A) ILC1, (B) ILC3, (C) ex-ILC3, (D) M1/CD45, (E) M2/CD45, and (F) M1/M2 ratio were investigated. It is a graph showing.
  • Guar gum is a water-soluble natural polysaccharide obtained from the endosperm (more precisely, the cotyledons) of guar beans, and has two molecules of mannose linked in a straight chain and one molecule of galactose as a side chain. It is a polysaccharide and has an average molecular weight of about 2.0 ⁇ 10 5 to 3.0 ⁇ 10 5 . Guar gum is known to have physiological effects such as blood sugar level elevation inhibitory effect, cholesterol lowering effect, and bowel movement improving effect.
  • the guar gum hydrolyzate is made from beans derived from the annual leguminous plant guar (scientific name: Cyanopsis tetragoloba), which is used for food in India, Pakistan, etc., and hydrolyzes the galactomannan polysaccharide contained in the endosperm. and water-soluble dietary fiber obtained by reducing the molecular weight.
  • the method for hydrolyzing guar gum is not particularly limited and may be an enzymatic decomposition method, an acid decomposition method, or the like.
  • the enzyme used in the enzymatic decomposition method is not particularly limited as long as it is an enzyme that hydrolyzes linear mannose chains, but it is preferable to use ⁇ -mannanase derived from bacteria belonging to the genus Aspergillus or Rhizopus.
  • the upper limit of the average molecular weight distribution of the guar gum decomposition product is 2 ⁇ 10 5 or less, preferably 1.0 ⁇ 10 5 or less, more preferably 2.5 ⁇ 10 4 or less.
  • the lower limit of the average molecular weight distribution of the guar gum decomposition product is 1.8 ⁇ 10 2 or more, preferably 3.0 ⁇ 10 3 or more.
  • the method for measuring the molecular weight distribution is not particularly limited . There is a method using a filtration chromatography method and the like.
  • the guar gum decomposition product of the present invention contains 70% by mass or more, preferably 80% by mass or more of those having the average molecular weight within the above range.
  • Galactose is a type of monosaccharide classified as aldohexose, and has a molecular formula of C 6 H 12 O 6 and a molecular weight of 180 (both of which are the same as glucose).
  • the configuration is 2-position (second from the top in the Fisher projection formula), -OH at 5-position is in the same direction, 3-position and 4-position are in the opposite direction, and the configuration at 5-position of D-galactose is D-glycerol Same as aldehyde.
  • Mannose is a type of monosaccharide classified as aldohexose, and has a molecular formula of C 6 H 12 O 6 and a molecular weight of 180 (both of which are the same as glucose).
  • the steric configuration is such that the --OH at the 2- and 3-positions are in the same direction and the 4- and 5-positions are in the opposite direction, and the steric configuration at the 5-position of D-mannose is the same as that of D-glyceraldehyde.
  • Mannose is poorly metabolized in humans and hardly enters the glycolysis system when orally ingested.
  • the oligosaccharide content was 6 to 15% by mass (15% by mass or less) according to the gel filtration chromatograph analysis chart.
  • Amino acid composition in proteins can be measured by a known method using, for example, HPLC.
  • Asparagine and glutamine are converted to aspartic acid and glutamic acid, respectively, during protein hydrolysis in pretreatment for amino acid analysis, and asparagine and aspartic acid, and glutamic acid and glutamine cannot be distinguished during measurement. Therefore, these are collectively quantified as aspartic acid and glutamic acid.
  • “Sarcopenia” means a condition (disease) in which muscles are reduced due to aging, lack of exercise, disease, or the like. If you don't use your muscles due to lack of exercise, your muscles will weaken and become thin, which not only invites further lack of exercise, but also causes bedridden. Sarcopenia increases the risk of diabetes (especially type 2 diabetes) and hypertension, and has other effects such as decreased walking speed, increased risk of falls, and increased mortality. . “Sarcopenic obesity” means a state in which obesity occurs due to an increase in fat when calorie consumption is low relative to calorie intake in sarcopenia.
  • the present invention has an improvement effect on sarcopenic obesity induced by diabetes (particularly elderly type 2 diabetes) among various diseases.
  • the composition for suppressing sarcopenia obesity of the present invention can be orally ingested as it is or mixed with foods, beverages, and the like.
  • the dose of the composition for suppressing sarcopenia obesity when taken orally is not particularly limited, but is 0.5 g to 70 g (preferably 3 g to 30 g, more preferably 6 g to 18 g) per adult per day.
  • guar gum degradation product (PHGG)>
  • Example 1 After adjusting the pH to 4.5 by adding 0.1N hydrochloric acid to 900 g of water, 0.2 g of commercially available ⁇ -mannanase derived from bacteria belonging to the genus Aspergillus and 100 g of guar gum powder were added and mixed. The mixture was reacted at 40° C.-45° C. for 24 hours. After the reaction, the enzyme was deactivated by heating at 90°C for 15 minutes. The reaction solution was separated by suction filtration, and the clear solution obtained by removing insoluble matter was concentrated under reduced pressure (Yamato evaporator). A solid content of 20% by mass was obtained.
  • Example 2 After adjusting the pH to 3 by adding 0.1N hydrochloric acid to 900 g of water, 0.15 g of commercially available ⁇ -mannanase derived from bacteria belonging to the genus Aspergillus and 100 g of guar gum powder were added and mixed. The mixture was reacted at 40° C.-45° C. for 24 hours. After the reaction, the enzyme was deactivated by heating at 90°C for 15 minutes. The reaction solution was separated by suction filtration, and the clear solution obtained by removing insoluble matter was concentrated under reduced pressure (Yamato evaporator). A solid content of 20% by mass was obtained.
  • the content ratio of galactose and mannose was measured to be 1:1.8.
  • the dietary fiber content was measured by enzyme-HPLC method and found to be 89% by weight.
  • the oligosaccharide content was 10% by mass.
  • Example 3 After adjusting the pH to 4 by adding 0.1N hydrochloric acid to 900 g of water, 0.25 g of commercially available ⁇ -mannanase derived from bacteria belonging to the genus Aspergillus and 100 g of guar gum powder were added and mixed. The mixture was reacted at 50° C.-55° C. for 12 hours. After the reaction, the enzyme was deactivated by heating at 90°C for 15 minutes. The reaction solution was separated by suction filtration, and the clear solution obtained by removing insoluble matter was concentrated under reduced pressure (Yamato evaporator). A solid content of 20% by mass was obtained.
  • Example 4 A guar gum hydrolyzate was prepared according to the examples of JP-A-5-117156 (page 4, line 3 to page 4, line 10). When the average molecular weight was determined according to Example 1, it was 5.5 ⁇ 10 3 .
  • ND group normal diet group
  • FFD group fiber-free diet group
  • PHGG group PHGG-added diet group
  • Glucose and Insulin Tolerance Tests Weekly mice were fasted overnight for 14 hours and weighed. At 15 weeks of age, an intraperitoneal glucose tolerance test (iPGTT: 2 g/kg body weight) and an insulin tolerance test (ITT: 0.75 U/kg body weight) were performed after fasting for 14 hours and 5 hours, respectively. (manufactured by Sanwa Hong Kong Kenko Co., Ltd.)) was used to measure blood glucose. The area under the curve (AUC) of the iPGTT and ITT results were analyzed respectively.
  • iPGTT 2 g/kg body weight
  • ITT insulin tolerance test
  • Weight Measurement of Soleus and Plantar Muscles The weights of the soleus (Soleus) and plantar (Planaris) muscles of each individual were measured. Each muscle weight was normalized to body weight. 6. Muscle Histology Soleus and plantar muscles were obtained, fixed in 10% buffered formaldehyde, and embedded in paraffin. Muscle sections were prepared and stained with hematoxylin and eosin staining. Images were taken with a BZ-X710 fluorescence microscope (manufactured by Keyence Corporation). Cross-sectional areas were measured with Image J (NIH). 7. Liver weight and visceral fat weight Liver weight and visceral fat weight (Epididymal Fat Weight) were measured. All were normalized to body weight. 8.
  • Liver histology Livers were harvested, fixed in 10% buffered formaldehyde, and embedded in paraffin. Liver sections were prepared and stained with hematoxylin-eosin (HE), Masson's trichrome stain (MT) and Oil-red O. Images were taken with a BZ-X710 fluorescence microscope (manufactured by Keyence Corporation). In addition, the non-alcoholic fatty liver disease (NAFLD) activity score (NAS) was used to assess the severity of NAFLD.
  • HE hematoxylin-eosin
  • MT Masson's trichrome stain
  • Oil-red O Images were taken with a BZ-X710 fluorescence microscope (manufactured by Keyence Corporation).
  • NAFLD activity score was used to assess the severity of NAFLD.
  • a sample of rectal feces (20 mg), serum (50 ⁇ L), and plantar muscle (20 mg) was added to 500 ⁇ L of acetonitrile and 500 ⁇ L of diluted water, ground in a ball mill at 4000 rpm for 2 minutes, and then shaken at 37° C. at 1000 rpm for 30 minutes. and centrifuged at 14000 rpm for 3 minutes at room temperature.
  • Supernatant (500 ⁇ L) was added to 500 ⁇ L of acetonitrile and shaken at 1000 rpm at 37° C. for 3 minutes. Then, it was centrifuged at 14000 rpm for 3 minutes at room temperature, and the pH was adjusted to 8 with 0.1 mol/L NaOH to extract SCFA.
  • SCFA and amino acid concentrations were automatically measured by an online solid phase extraction (SPE) method using an SPE-GC system SGI-M100 (manufactured by Icety Science).
  • a CP-Sil88 for FAME 100 m ⁇ 0.25 mm inner diameter ⁇ 0.20 ⁇ m film thickness (manufactured by Agilent Technologies) capillary column was used for the separation of fatty acids. The temperature of the column was maintained at 100° C. for 4 minutes, then increased at 3° C./min to 240° C. and held for 7 minutes. Samples were injected in split mode with a split ratio of 5:1. Each fatty acid methyl ester was detected with the selected ion monitoring mode. All results were normalized to the peak height of the C17:0 internal standard.
  • RNA expression analysis in jejunum and soleus muscle The jejunum and soleus muscle samples obtained by dissection were homogenized in an ice-cold QIAzol Lysis reagent (manufactured by Qiagen) to isolate total RNA.
  • Total RNA 0.5 ⁇ g was reverse transcribed using a high-capacity cDNA reverse transcription kit (manufactured by Applied Biosystems). The reverse transcription reaction was carried out at 37°C for 120 minutes and reverse transcription inactivation was carried out at 85°C for 5 minutes.
  • RT-PCT Real-time reverse transcription-polymerase chain reaction
  • RT-PCT was used to determine the mRNA expression levels of Trim63, Fbxo32, Tnfa, Il6, Foxo1 and Hdac4 for soleus muscle and Tnfa, Il6, Il1B, Cd36 and Il22 for jejunum. Expression levels were quantified.
  • RT-PCT was performed using TaqMan Fast Advanced Master Mix (manufactured by Applied Biosystems). The following method was used as PCT conditions. One cycle consisted of synthesis reaction at 50°C for 2 minutes and denaturation at 95°C for 20 seconds. Relative expression levels of each target gene were normalized to Gapdh threshold cycle (CT) values and quantified using the comparative threshold cycle 2- ⁇ CT method. Relative values were calculated with the signal of ND mouse set to 1.0.
  • CT Gapdh threshold cycle
  • APCT-CD45.2 (17045482; clone: 104, 1/50)
  • PE-F4/80 (12480182; clone: BM8, 1/50)
  • APC-Cy7-CD11b (47011282; clone: M1/70, 1/50)
  • FITC-CD206 MA516870; clone: MR5D3, 1/50
  • PE-CY7-CD11c 25011482; clone: N418, 1/50
  • FIG. 1 shows changes in body weight of the ND group, FFD group and PHGG group.
  • Fig. 2 shows changes in blood glucose level after each test of iPGTT and ITT performed at 15 weeks of age, and AUC is shown in Fig. 3, respectively.
  • the blood glucose level increased in all tests, and it was considered that diabetes, which is characteristic of Db/Db mice, was developed (or was developing).
  • the PHGG group the blood glucose level was significantly (p ⁇ 0.01) lower than the ND group in all tests, and impaired glucose tolerance was improved. 2.
  • FIG. 1 shows changes in body weight of the ND group, FFD group and PHGG group.
  • Fig. 2 shows changes in blood glucose level after each test of iPGTT and ITT performed at 15 weeks of age, and AUC is shown in Fig. 3, respectively.
  • the blood glucose level increased in all tests, and it was considered that diabetes, which is characteristic of Db/Db mice, was developed (or was developing).
  • the PHGG group the blood glucose level was significantly (
  • FIG. 4 shows changes in oxygen partial pressure (VO 2 ) and carbon dioxide partial pressure (VCO 2 ) for each group over time.
  • FIG. 5 shows the average values of VO2 and VCO2 during the light period (12 hours) and the dark period (12 hours).
  • the PHGG group showed a significant (p ⁇ 0.05) increase in basal metabolism compared to the ND and FFD groups.
  • Grip Strength Measurement FIG. 6(A) shows the grip strength measurement results, and FIG. 6(B) shows the results normalized to the body weight. The PHGG group had significantly stronger grip strength than the ND and FFD groups.
  • FIG. 7(A) shows the weight of the soleus muscle in each group, and FIG. 7(B) shows the results normalized to body weight.
  • FIG. 8(A) shows the plantar muscle weight of each group, and FIG. 8(B) shows the results normalized to body weight.
  • the PHGG group had significantly heavier soleus and plantar muscle weights than the ND and FFD groups.
  • Muscle histology FIG. 9 shows histology of the soleus and plantar muscles in each group (representative micrographs).
  • FIG. 10 shows the results of examining the cross-sectional area of each muscle.
  • the PHGG group had a significantly larger muscle cross-sectional area than the ND and FFD groups. 6.
  • FIG. 11(A) shows liver weight
  • Fig. 11(B) shows liver weight normalized to body weight
  • FIG. 12(A) shows visceral fat mass
  • FIG. 12(B) shows visceral fat mass normalized to body weight.
  • the PHGG group had significantly larger liver weights than the ND and FFD groups.
  • the PHGG group significantly decreased the normalized visceral fat mass compared to the ND group and the FFD group.
  • FIG. 13 shows representative micrographs of liver tissues taken from each group stained with hematoxylin-eosin (HE), Masson's trichrome staining (MT) and Oil-red O. showed that.
  • FIG. 14 shows the results of examining the NAS and Oil Red O areas for the three groups. The PHGG group significantly improved fatty liver compared to the ND group and FFD group.
  • FIG. 15 shows the results of examining ALT, T-Chol, TG and NEFA in blood samples. For all test items, the PHGG group showed significantly lower values than the ND group or the FFD group. Thus, the PHGG group significantly improved lipid metabolism disorders. 9.
  • FIG. 16 shows acetic acid, propanoic acid and butanoic acid concentrations in feces.
  • FIG. 17 shows the concentration of each short-chain fatty acid in serum. All short-chain fatty acids were significantly elevated in feces and serum in the PHGG group compared to the ND group or the FFD group.
  • FIG. 18 shows the concentrations of valine, leucine, isoleucine, threonine, methionine, phenylalanine, lysine and glutamic acid among amino acids in muscle. These amino acids are involved in muscle protein synthesis and inhibition of degradation. All amino acids were significantly increased in the PHGG group compared to the ND group and the FFD group.
  • FIG. 19 shows palmitic acid concentrations in feces, serum, and muscles.
  • the PHGG group showed a significant increase in feces and a significant decrease in serum and muscle compared to the ND and FFD groups.
  • FIG. 20 shows the results of gene expression analysis in jejunum
  • FIG. 21 shows the results of gene expression analysis in muscle. In the jejunum, the expression of inflammation-related genes (tnfa, il6, il1b, cd36) was significantly reduced in the PHGG group compared to the ND group or FFD group.
  • FIG. 22 shows the results of measuring ILC1, ILC3, ex-ILC3, M1/CD45, M2/CD45 and the M1/M2 ratio. Inflammatory cells and factors related thereto (ILC1, ex-ILC3, M1/CD45) were significantly decreased in the PHGG group compared to the ND group and FFD group. In addition, the PHGG group significantly increased factors (IL22, IL3, M2 macrophages) that resolve inflammation.
  • PHGG PHGG was effective against both sarcopenia, diabetes and obesity. That is, improvement of impaired glucose tolerance, increased basal metabolism, improved grip strength/decreased muscle mass, decreased visceral fat content, improved liver fat, and improved lipid metabolism disorders were observed.
  • the mechanism is increased short-chain fatty acids in feces and blood, increased branched-chain amino acids in muscles, decreased saturated fatty acids in blood, increased excretion of saturated fatty acids, and expression of muscle atrophy-related genes in skeletal muscle. decreased expression of inflammation-related genes in the small intestine, and decreased inflammatory cells in the lamina intestinal of the small intestine.
  • a novel composition for suppressing sarcopenic obesity and a sarcopenic obesity preventive and/or therapeutic composition containing the same for improving sarcopenic obesity induced by diabetes could be provided. .

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PCT/JP2022/035034 2021-10-12 2022-09-20 サルコペニア肥満抑制組成物、及びこれを含有し糖尿病によって誘導されたサルコペニア肥満を改善するための予防及び／又は治療用組成物 WO2023063033A1 (ja)

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