WO2018051471A1 - Fat accumulation inhibitor, preadipocyte differentiation inhibitor, visceral-fat-reducing agent, and food or beverage for visceral-fat reduction - Google Patents

Fat accumulation inhibitor, preadipocyte differentiation inhibitor, visceral-fat-reducing agent, and food or beverage for visceral-fat reduction Download PDF

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WO2018051471A1
WO2018051471A1 PCT/JP2016/077315 JP2016077315W WO2018051471A1 WO 2018051471 A1 WO2018051471 A1 WO 2018051471A1 JP 2016077315 W JP2016077315 W JP 2016077315W WO 2018051471 A1 WO2018051471 A1 WO 2018051471A1
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fat
iodine
egg
visceral
inhibitor
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PCT/JP2016/077315
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French (fr)
Japanese (ja)
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次郎 横山
恵美 森岡
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日本農産工業株式会社
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Priority to KR1020197010469A priority Critical patent/KR102239331B1/en
Priority to JP2018539460A priority patent/JP6752285B2/en
Priority to PCT/JP2016/077315 priority patent/WO2018051471A1/en
Publication of WO2018051471A1 publication Critical patent/WO2018051471A1/en

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L15/00—Egg products; Preparation or treatment thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/18—Iodine; Compounds thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L15/00—Egg products; Preparation or treatment thereof
    • A23L15/30—Addition of substances other than those covered by A23L15/20 – A23L15/25
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • 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
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • 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
    • A23L33/16—Inorganic salts, minerals or trace elements
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/57—Birds; Materials from birds, e.g. eggs, feathers, egg white, egg yolk or endothelium corneum gigeriae galli
    • 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
    • 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
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/332—Promoters of weight control and weight loss

Definitions

  • the present disclosure relates to a fat accumulation inhibitor, an agent for inhibiting differentiation of preadipocytes, a visceral fat reducing agent, and a food and drink for reducing visceral fat.
  • Adipocytes are cells that originate from mesodermal stem cells and differentiate through fat precursor cells, etc., and are classified into white adipocytes that control fat synthesis, accumulation, and release, and brown adipocytes that control heat production.
  • Obesity is a condition where excessive fat is accumulated in white fat cells. Therefore, in order to prevent or improve obesity, it is effective to suppress fat accumulation in white adipocytes. In recent years, it has been clarified that the number of white adipocytes also increases after adulthood, and in order to prevent or ameliorate obesity, it is also possible to suppress the differentiation of preadipocytes into white adipocytes. It is valid.
  • visceral fat obesity is roughly classified into subcutaneous fat type obesity and visceral fat type obesity.
  • visceral fat obesity is known to increase the risk of diabetes, arteriosclerosis, hypertension, cerebral infarction, dyslipidemia and the like. For this reason, it is important to prevent or improve visceral fat type obesity among obesity.
  • Patent Document 1 describes an adipocyte fat accumulation inhibitor containing an aqueous ethanol extract of Kawaratake as an active ingredient.
  • Patent Document 2 describes a preadipocyte differentiation inhibitor containing lotus germ and yacon extracts, and an anti-obesity agent containing this differentiation inhibitor as an active ingredient.
  • Patent Document 3 describes a body fat accumulation inhibitor, visceral fat accumulation inhibitor and the like containing egg white as an active ingredient.
  • the body fat accumulation inhibitor and visceral fat accumulation inhibitor described in Patent Document 3 contain food materials as active ingredients, and are considered to be excellent in safety when continuously administered or ingested. However, the effect is not sufficient, and a search for a new active ingredient that is effective and excellent in safety has been desired.
  • the present disclosure provides a novel fat accumulation inhibitor, an adipose precursor cell differentiation inhibitor, a visceral fat reducing agent, and a food and drink for reducing visceral fat using an effective ingredient that is effective and excellent in safety. Is an issue.
  • a fat accumulation inhibitor comprising, as an active ingredient, an egg containing 4.2 mass ppm or more of iodine.
  • An agent for inhibiting differentiation of adipose precursor cells comprising as an active ingredient an egg containing 4.2 mass ppm or more of iodine.
  • a visceral fat reducing agent comprising, as an active ingredient, an egg containing 4.2 ppm by mass or more of iodine.
  • a food or drink for reducing visceral fat comprising an egg containing 4.2 ppm by mass or more of iodine as an active ingredient.
  • a visceral fat reducing agent that is used so that an egg yolk extract containing an iodinated peptide is an active ingredient and is administered in an amount of 300 ⁇ g or more per day.
  • a novel fat accumulation inhibitor an adipose precursor cell differentiation inhibitor, a visceral fat reducing agent, and a food and drink for reducing visceral fat using an effective ingredient that is effective and excellent in safety. Can do.
  • FIG. 5 is a graph showing the glycerol-3-phosphate dehydrogenase (GPDH) activity of adipocytes when an egg yolk extract (IY) containing high iodine content or an egg yolk extract (OY) of normal egg is added to the medium. is there.
  • GPDH glycerol-3-phosphate dehydrogenase
  • FIG. It is a figure which shows the expression level (relative value) of the adipogenin gene of an adipocyte when the egg yolk extract (IY) or egg yolk extract (OY) of a normal egg is added in a culture medium. It is a figure which shows the expression level (relative value) of the leptin gene of an adipocyte when the egg yolk extract (IY) or egg yolk extract (OY) of a normal egg is added in a culture medium. It is a figure which shows the expression level (relative value) of the adiponectin gene of an adipocyte when the egg yolk extract (IY) or egg yolk extract (OY) of a normal egg is added in a culture medium.
  • PPAR Peroxisome Proliferator Activated Receptor
  • a numerical range indicated by using “to” indicates a range including the numerical values described before and after “to” as the minimum value and the maximum value, respectively.
  • the fat accumulation inhibitor, the precursor of preadipocytes, the visceral fat reducing agent, and the food and drink for reducing visceral fat according to the first embodiment are all eggs containing 4.2 ppm by mass or more of iodine (hereinafter referred to as “bird eggs”). , Also referred to as “iodine-rich egg”) as an active ingredient.
  • Examples of avian eggs include chicken eggs such as chickens, rabbits, rib chickens and ducks, with chicken eggs being preferred. Eggs with high iodine content can be obtained by feeding birds with an increased iodine content by blending an iodine source and increasing the iodine content in the eggs.
  • iodine sources include iodine compounds such as calcium iodate, potassium iodate, potassium iodide, sodium iodate, thymol iodide, copper iodide, hypoiodosalicylic acid, calcium periodate, calcium iodobihemate; Examples include seaweeds containing a high content of iodine such as kelp or processed products thereof.
  • the rate of migration of iodine to eggs, etc. it is preferable to use at least one selected from the group consisting of calcium iodate, potassium iodate, and potassium iodide as the iodine source. Moreover, it is more preferable to use a seaweed together with at least one selected from the group consisting of calcium iodate, potassium iodate, and potassium iodide.
  • the amount of iodine given to birds can be adjusted as appropriate depending on the type of bird.
  • the iodine intake is preferably 5 mg to 250 mg per bird per day, and more preferably 5 mg to 15 mg iodine per bird per day.
  • the iodine content in the feed is preferably 50 mass ppm to 2500 mass ppm, more preferably 50 mass ppm to 150 mass ppm. It is more preferable.
  • the target high-iodine egg is produced after about one week.
  • a feed containing about 50 ppm by mass of iodine is given to a laying hen, eggs containing about 300 ⁇ g of iodine per piece are produced.
  • the iodine content of the high-iodine egg is not particularly limited as long as it is 4.2 mass ppm or more with respect to the total amount of the edible portion, and is preferably 4.2 mass ppm to 20.0 mass ppm, for example.
  • the iodine content of the high-iodine egg is not particularly limited as long as it is 4.2 mass ppm or more with respect to the total amount of the edible portion, and is preferably 4.2 mass ppm to 20.0 mass ppm, for example.
  • a decrease in the egg-laying rate tends to be suppressed.
  • the edible part of shell eggs circulated mainly in the market is about 45 to 66 g per piece
  • the iodine content of 4.2 to 20.0 ppm by weight is about 200 ⁇ g per piece.
  • the required amount of iodine in egg-laying hens is 0.2 mg per 1 kg of feed (according to Japanese feed standard poultry (2011 version)), and the actual iodine content in commercially available feed is 0.3 mg to 2.0 mg per 1 kg of feed. It has become.
  • the iodine content of normal eggs produced from laying hens bred using this commercial feed is about 9 ⁇ g per piece (according to the Japanese Food Standards Ingredients 2015 edition (7th edition)), at most one piece. About 30 ⁇ g per unit.
  • ⁇ ⁇ ⁇ Eggs with high iodine content are also available as commercial products.
  • “Iodo Egg Light” (“Iodo Egg” is a registered trademark) of Nippon Agricultural Industry Co., Ltd. can be mentioned.
  • the fat accumulation inhibitor, the preadipocyte differentiation inhibitor, the visceral fat reducing agent, and the food and drink for reducing visceral fat according to the first embodiment may contain the whole egg of an iodine-rich egg as an active ingredient. Further, since most of iodine in the egg containing high iodine is contained in the yolk as an iodide peptide bound to the peptide, the fat accumulation inhibitor, the precursor of fat precursor cells, the visceral fat reduction according to the first embodiment.
  • the agent and food and drink for reducing visceral fat may contain egg yolk of a high iodine content egg as an active ingredient, or may contain an egg yolk extract as an active ingredient.
  • the egg yolk extract is not particularly limited as long as it contains an iodide peptide in egg yolk.
  • the whole egg, egg yolk, and egg yolk extract of the egg with high iodine content may be subjected to treatments such as drying, concentration, powdering, and granulating as necessary.
  • the dosage form of the fat accumulation inhibitor, the adipocyte differentiation inhibitor, and the visceral fat reducing agent of the first embodiment is not particularly limited, and examples thereof include powders, granules, tablets, capsules, syrups, and emulsions. .
  • the fat accumulation inhibitor, the preadipocyte differentiation inhibitor, and the visceral fat-reducing agent of the first embodiment further contain various excipients, binders, disintegrants, solvents, and the like depending on the dosage form. May be.
  • the dose and administration period of the fat accumulation inhibitor of the first embodiment, the differentiation inhibitor of preadipocytes, and the visceral fat reducing agent, and the intake and intake period of the food and drink for reducing visceral fat of the first embodiment are: There is no particular limitation as long as the intended effect is achieved. As an example, it is preferable to continue the dose or intake amount for which the iodine amount per day is 300 ⁇ g or more for 1 month or more, and it is more preferable to continue for 3 months or more.
  • the upper limit of the dose or intake can be set based on the tolerable upper limit of iodine. As an example, the amount of iodine per day can be set to a dose or intake amount of 3000 ⁇ g or less.
  • the obesity is prevented or improved by administering the fat accumulation inhibitor of the first embodiment, the differentiation inhibitor of preadipocytes, or the visceral fat reducing agent, or taking the food or drink for reducing visceral fat of the first embodiment.
  • the following method is also provided. (1) A method for inhibiting fat accumulation, comprising administering an effective amount of a bird egg containing iodine of 4.2 mass ppm or more to a subject. (2) A method for inhibiting differentiation of preadipocytes, comprising administering to a subject an effective amount of an egg containing 4.2 mass ppm or more of iodine.
  • a visceral fat reduction method comprising administering to a subject an effective amount of an egg containing 4.2 ppm by mass or more of iodine.
  • a visceral fat reduction method comprising ingesting an effective amount of an egg containing 4.2 ppm by mass or more of iodine.
  • a method for preventing or improving obesity comprising administering to a subject an effective amount of a bird egg containing iodine of 4.2 mass ppm or more.
  • a method for preventing or improving obesity comprising ingesting an effective amount of a bird egg containing iodine of 4.2 mass ppm or more.
  • the visceral fat reducing agent according to the second embodiment is used so that egg yolk extract containing an iodinated peptide is an active ingredient and is administered in an amount of 300 ⁇ g or more per day.
  • the eggs include chicken eggs such as chickens, rabbits, rib chickens and ducks, and chicken eggs are preferred.
  • the bird egg may be a normal egg or the above-described high-iodine egg, and the above-described high-iodine egg is preferable in terms of high iodine content.
  • the egg yolk extract is not particularly limited as long as it contains an iodide peptide in egg yolk.
  • the egg yolk extract may be subjected to treatments such as drying, concentration, pulverization, and granulation as necessary.
  • the dosage form of the visceral fat reducing agent of the second embodiment is not particularly limited, and examples thereof include powders, granules, tablets, capsules, syrups, and emulsions.
  • the visceral fat reducing agent of the second embodiment may further contain various excipients, binders, disintegrants, solvents and the like depending on the dosage form.
  • the dose of the visceral fat reducing agent according to the second embodiment is not particularly limited as long as the dose per day is 300 ⁇ g or more.
  • the upper limit value of the dose can be set based on the tolerable upper limit amount of iodine. As an example, it can be set as the dosage which the iodine amount per day will be 3000 micrograms or less.
  • the administration period of the visceral fat reducing agent of the second embodiment is not particularly limited as long as the intended effect is exhibited. As an example, it is preferable to administer continuously for 1 month or more, and it is more preferable to administer continuously for 3 months or more.
  • a visceral fat reduction method comprising administering 300 ⁇ g or more of an egg yolk extract containing an iodinated peptide as an iodine amount per day.
  • a method for preventing or improving obesity comprising administering 300 ⁇ g or more of an egg yolk extract containing an iodinated peptide as iodine amount per day.
  • mice fat precursor cells 3T3-L1 were differentiated into adipocytes, and the amount of fat accumulated in the adipocytes was measured.
  • 3T3-L1 cells usually show fibroblast-like morphology under culture conditions, but form insulin granules and differentiate into adipocytes by applying insulin stimulation after confluence. .
  • 3T3-L1 cells were seeded in a 6-well plate and maintained by DMEM (Dulbecco's Modified Modified Eagle Medium) containing 10 v / v% FBS (Fetal Bovine Serum) until 2 days after confluence. The medium was changed every 48 hours. Next, the medium was changed to DMEM containing 10 v / v% FBS, 0.5 mM isobutylmethylxanthine, 1 ⁇ M dexamethasone, and 1.7 ⁇ M insulin, and differentiation into adipocytes was induced by culturing for 48 hours. Subsequently, the medium was replaced with DMEM containing 10 v / v% FBS.
  • DMEM Dulbecco's Modified Modified Eagle Medium
  • FBS Fetal Bovine Serum
  • egg yolk extract (IY) containing high iodine content or egg yolk extract (OY) of normal egg was added to a final concentration of 5 ⁇ g / mL, 10 ⁇ g / mL, or 50 ⁇ g / mL, and cultured for 10 days. .
  • the medium was changed every 48 hours.
  • adipocytes After 10 days of culture, the differentiated adipocytes were washed 3 times with PBS and fixed with 10 v / v% paraformaldehyde solution for 10 minutes or more. After fixation, adipocytes were washed twice with PBS and stained with 0.5 w / v% Oil Red O solution (Sigma-Aldrich) at 37 ° C. Thereafter, the amount of fat accumulated in the fat cells was evaluated by measuring the absorbance at a wavelength of 570 nm.
  • FIG. 1 shows the evaluation results of the amount of accumulated fat in fat cells.
  • IY egg yolk extract
  • OY egg yolk extract
  • Example 2 In Experimental Example 2, the amount of fat accumulated in fat cells was measured in the same manner as in Example 1 except that sodium iodide was used instead of the egg yolk extract. Sodium iodide was added to the medium so that the final concentration of iodide ions was 10 ⁇ 9 M, 10 ⁇ 8 M, 10 ⁇ 7 M, or 10 ⁇ 6 M.
  • Fig. 2 shows the evaluation results of the amount of accumulated fat in fat cells. As shown in FIG. 2, even when sodium iodide was added to the medium, the amount of fat accumulated in the fat cells did not change significantly. From the results of Experimental Examples 1 and 2, the fat accumulation suppression effect by the egg yolk extract (IY) of the high iodine content egg is not due to iodine in an ionic state, but due to the iodide peptide contained in the high iodine content egg. It is suggested that there is.
  • IY egg yolk extract
  • 3T3-L1 was prepared using a medium supplemented with egg yolk extract (IY) containing high iodine content or egg yolk extract (OY) of normal egg to a final concentration of 50 ⁇ g / mL.
  • the cells were cultured for 10 days to obtain adipocytes.
  • the adipocytes (Day 10) after 10 days of culturing were washed with PBS, the cells were crushed, and GPDH activity was measured for the cell lysate using a GPDH activity measurement kit (Cell Garage).
  • the obtained measurement results were corrected with the amount of protein in the cell disruption solution.
  • GPDH activity was also measured in the same manner for cells (Day 0) before 10 days of culture.
  • Fig. 3 shows the measurement results of GPDH activity.
  • the GPDH activity was compared to the case where the egg yolk extract (OY) of normal egg was added to the medium. Significantly decreased (p ⁇ 0.05).
  • 3T3-L1 was prepared using a medium supplemented with egg yolk extract (IY) containing high iodine content or egg yolk extract (OY) of normal egg to a final concentration of 50 ⁇ g / mL.
  • the cells were cultured for 10 days to obtain adipocytes.
  • Total RNA was extracted from adipocytes (Day 10) after 10 days of culture, and the expression level of each gene of PPAR- ⁇ 2, adipogenin, leptin, and adiponectin was measured by real-time reverse transcription PCR (Polymerase Chain ⁇ ⁇ ⁇ ⁇ Reaction) according to a conventional method. did.
  • the obtained measurement results were corrected with the expression level of ⁇ -actin gene as an internal standard. For comparison, the expression level of the gene was measured in the same manner for the cells (Day 0) before 10 days of culture.
  • FIGS. 4A to 4D show the measurement results (relative values) of the expression levels of each gene of PPAR- ⁇ 2, adipogenin, leptin, and adiponectin.
  • “ND” in FIGS. 4A to 4C means no detection.
  • FIGS. 4A to 4D when the egg yolk extract (IY) containing high iodine content is added to the medium, it is compared with the case where the egg yolk extract (OY) of normal egg is added to the medium.
  • PPAR- ⁇ 2 adipogenin, leptin, and adiponectin genes were significantly reduced (PPAR- ⁇ 2, adipogenin, and leptin: p ⁇ 0.05, adiponectin: p ⁇ 0.1).
  • Example 5 In Experimental Example 5, the subjects were divided into two groups to continuously ingest iodine-rich eggs or normal eggs, and the effect on body fat was evaluated by the double blind method. Eggs containing about 1300 ⁇ g of iodine per 100 g of edible portion (Nippon Agricultural Industrial Co., Ltd., “Iodo Egg Light”) were used as eggs with high iodine content. In addition, commercially available eggs were used as normal eggs.
  • the subjects were 56 men and women who were between 40 and 65 years old and had a BMI (Body Mass Index) of 25 kg / m 2 or more and less than 30 kg / m 2 , and the test group (male: 14 and female: 14) and the control group ( The group was divided into two groups: 14 males and 14 females.
  • the test group one iodine-rich egg per day was continuously ingested as a boiled egg for 12 weeks.
  • the control group 1 normal egg per day was continuously ingested as a boiled egg over 12 weeks.
  • various tests such as a blood test and a urine test, were performed and compared before and after the test.
  • Table 1 shows changes in the total fat area, visceral fat area, and subcutaneous fat area before and after the test.
  • Table 1 also shows blood total cholesterol (T-cho), triglyceride (TG), LDL (Low Density Lipoprotein) cholesterol (LDL-cho), HDL (High Density Lipoprotein) cholesterol (HDL-cho), free
  • T-cho blood total cholesterol
  • TG triglyceride
  • LDL Low Density Lipoprotein
  • HDL High Density Lipoprotein cholesterol
  • Table 1 shows the average value ⁇ standard error for each group.
  • the amount of total cholesterol, triglyceride, LDL cholesterol, and HDL cholesterol in blood related to lipid metabolism did not change significantly in either the test group or the control group.
  • the amounts of free triiodothyronine (FT3) and free thyroxine (FT4) in blood related to thyroid function did not change significantly in either the test group or the control group, and remained within the normal range. From these results, the visceral fat reduction effect by the iodine-rich egg is not due to the improvement of lipid metabolism function or thyroid function, but to the iodide peptide contained in the iodine-rich egg. It is suggested.

Abstract

Provided are a fat accumulation inhibitor, a preadipocyte differentiation inhibitor, a visceral-fat-reducing agent, and a food or beverage for visceral-fat reduction which each contain, as an active ingredient, a bird's egg containing iodine in an amount of 4.2 mass ppm or larger. Also provided is a visceral-fat-reducing agent which contains, as an active ingredient, an extract of the yolk of a bird's egg containing an iodinated peptide and which is administered at a dose of 300 μg or larger per day in terms of iodine amount.

Description

脂肪蓄積抑制剤、脂肪前駆細胞の分化抑制剤、内臓脂肪低減剤、及び内臓脂肪低減用飲食品Fat accumulation inhibitor, preadipocyte differentiation inhibitor, visceral fat reducing agent, and food and drink for reducing visceral fat
　本開示は、脂肪蓄積抑制剤、脂肪前駆細胞の分化抑制剤、内臓脂肪低減剤、及び内臓脂肪低減用飲食品に関する。 The present disclosure relates to a fat accumulation inhibitor, an agent for inhibiting differentiation of preadipocytes, a visceral fat reducing agent, and a food and drink for reducing visceral fat.
　脂肪細胞は、中胚葉系幹細胞から発生し、脂肪前駆細胞等を経て分化した細胞であり、脂肪の合成、蓄積、及び放出を司る白色脂肪細胞と、熱産生を司る褐色脂肪細胞とに分類される。 Adipocytes are cells that originate from mesodermal stem cells and differentiate through fat precursor cells, etc., and are classified into white adipocytes that control fat synthesis, accumulation, and release, and brown adipocytes that control heat production. The
　肥満とは、白色脂肪細胞に脂肪が過剰に蓄積された状態である。したがって、肥満を防止又は改善するためには、白色脂肪細胞への脂肪の蓄積を抑制することが有効である。また、近年、成人期以降においても白色脂肪細胞数が増加することが明らかとなっており、肥満を防止又は改善するには、脂肪前駆細胞等から白色脂肪細胞への分化を抑制することもまた有効である。 Obesity is a condition where excessive fat is accumulated in white fat cells. Therefore, in order to prevent or improve obesity, it is effective to suppress fat accumulation in white adipocytes. In recent years, it has been clarified that the number of white adipocytes also increases after adulthood, and in order to prevent or ameliorate obesity, it is also possible to suppress the differentiation of preadipocytes into white adipocytes. It is valid.
　一般に肥満は、皮下脂肪型肥満と内臓脂肪型肥満とに大別される。特に内臓脂肪型肥満は、糖尿病、動脈硬化、高血圧、脳梗塞、脂質異常症等のリスクを高めることが知られている。このため、肥満の中でも内臓脂肪型肥満を予防又は改善することが重要である。 Generally, obesity is roughly classified into subcutaneous fat type obesity and visceral fat type obesity. In particular, visceral fat obesity is known to increase the risk of diabetes, arteriosclerosis, hypertension, cerebral infarction, dyslipidemia and the like. For this reason, it is important to prevent or improve visceral fat type obesity among obesity.
　従来、肥満を防止又は改善する種々の技術が提案されている。
　例えば、特許文献１には、カワラタケのエタノール水抽出物を有効成分とする脂肪細胞の脂肪蓄積阻害剤が記載されている。
　特許文献２には、ハス胚芽及びヤーコンの抽出物を含有する前駆脂肪細胞の分化抑制剤、及びこの分化抑制剤を有効成分として含有する抗肥満剤が記載されている。
　特許文献３には、卵白を有効成分として含有する体脂肪蓄積抑制剤、内臓脂肪蓄積抑制剤等が記載されている。 Conventionally, various techniques for preventing or improving obesity have been proposed.
For example, Patent Document 1 describes an adipocyte fat accumulation inhibitor containing an aqueous ethanol extract of Kawaratake as an active ingredient.
Patent Document 2 describes a preadipocyte differentiation inhibitor containing lotus germ and yacon extracts, and an anti-obesity agent containing this differentiation inhibitor as an active ingredient.
Patent Document 3 describes a body fat accumulation inhibitor, visceral fat accumulation inhibitor and the like containing egg white as an active ingredient.
特許第４３６３８２５号公報Japanese Patent No. 4363825 特許第４６７５７８１号公報Japanese Patent No. 46575781 特開２０１１－２２５４９６号公報JP 2011-225496 A
　特許文献３に記載の体脂肪蓄積抑制剤及び内臓脂肪蓄積抑制剤は、食品素材を有効成分とするものであり、継続的に投与又は摂取する上での安全性に優れると考えられる。しかし、その効果は十分ではなく、効果的で且つ安全性に優れる新規な有効成分の探索が望まれていた。 The body fat accumulation inhibitor and visceral fat accumulation inhibitor described in Patent Document 3 contain food materials as active ingredients, and are considered to be excellent in safety when continuously administered or ingested. However, the effect is not sufficient, and a search for a new active ingredient that is effective and excellent in safety has been desired.
　そこで、本開示は、効果的で且つ安全性に優れる有効成分を用いた新規な脂肪蓄積抑制剤、脂肪前駆細胞の分化抑制剤、内臓脂肪低減剤、及び内臓脂肪低減用飲食品を提供することを課題とする。 Therefore, the present disclosure provides a novel fat accumulation inhibitor, an adipose precursor cell differentiation inhibitor, a visceral fat reducing agent, and a food and drink for reducing visceral fat using an effective ingredient that is effective and excellent in safety. Is an issue.
　上記課題を解決するための具体的な手段には、以下の実施態様が含まれる。
＜１＞　４．２質量ｐｐｍ以上のヨウ素を含有する鳥卵を有効成分とする脂肪蓄積抑制剤。
＜２＞　４．２質量ｐｐｍ以上のヨウ素を含有する鳥卵を有効成分とする脂肪前駆細胞の分化抑制剤。
＜３＞　４．２質量ｐｐｍ以上のヨウ素を含有する鳥卵を有効成分とする内臓脂肪低減剤。
＜４＞　４．２質量ｐｐｍ以上のヨウ素を含有する鳥卵を有効成分とする内臓脂肪低減用飲食品。
＜５＞　ヨウ化ペプチドを含有する鳥卵の卵黄抽出物を有効成分とし、１日当たりのヨウ素量として３００μｇ以上投与されるように用いられる内臓脂肪低減剤。 Specific means for solving the above problems include the following embodiments.
<1> A fat accumulation inhibitor comprising, as an active ingredient, an egg containing 4.2 mass ppm or more of iodine.
<2> An agent for inhibiting differentiation of adipose precursor cells, comprising as an active ingredient an egg containing 4.2 mass ppm or more of iodine.
<3> A visceral fat reducing agent comprising, as an active ingredient, an egg containing 4.2 ppm by mass or more of iodine.
<4> A food or drink for reducing visceral fat, comprising an egg containing 4.2 ppm by mass or more of iodine as an active ingredient.
<5> A visceral fat reducing agent that is used so that an egg yolk extract containing an iodinated peptide is an active ingredient and is administered in an amount of 300 μg or more per day.
　本開示によれば、効果的で且つ安全性に優れる有効成分を用いた新規な脂肪蓄積抑制剤、脂肪前駆細胞の分化抑制剤、内臓脂肪低減剤、及び内臓脂肪低減用飲食品を提供することができる。 According to the present disclosure, it is possible to provide a novel fat accumulation inhibitor, an adipose precursor cell differentiation inhibitor, a visceral fat reducing agent, and a food and drink for reducing visceral fat using an effective ingredient that is effective and excellent in safety. Can do.
ヨウ素高含有卵の卵黄抽出物（ＩＹ）又は普通卵の卵黄抽出物（ＯＹ）を培地中に添加した場合における、脂肪細胞への脂肪蓄積量（相対値）を示す図である。It is a figure which shows the fat accumulation amount (relative value) to an adipocyte when the egg yolk extract (IY) or the egg yolk extract (OY) of a normal egg is added in a culture medium. ヨウ化ナトリウムを培地中に添加した場合における、脂肪細胞への脂肪蓄積量（相対値）を示す図である。It is a figure which shows the fat accumulation amount (relative value) to a fat cell at the time of adding sodium iodide in a culture medium. ヨウ素高含有卵の卵黄抽出物（ＩＹ）又は普通卵の卵黄抽出物（ＯＹ）を培地中に添加した場合における、脂肪細胞のグリセロール－３－リン酸脱水素酵素（ＧＰＤＨ）活性を示す図である。FIG. 5 is a graph showing the glycerol-3-phosphate dehydrogenase (GPDH) activity of adipocytes when an egg yolk extract (IY) containing high iodine content or an egg yolk extract (OY) of normal egg is added to the medium. is there. ヨウ素高含有卵の卵黄抽出物（ＩＹ）又は普通卵の卵黄抽出物（ＯＹ）を培地中に添加した場合における、脂肪細胞のＰＰＡＲ（Peroxisome Proliferator Activated Receptor）－γ２遺伝子の発現量（相対値）を示す図である。Expression level of PPAR (Peroxisome Proliferator Activated Receptor) -γ2 gene in adipocytes when egg yolk extract (IY) containing high iodine content or egg yolk extract (OY) of normal egg is added to the medium (relative value) FIG. ヨウ素高含有卵の卵黄抽出物（ＩＹ）又は普通卵の卵黄抽出物（ＯＹ）を培地中に添加した場合における、脂肪細胞のアディポゲニン遺伝子の発現量（相対値）を示す図である。It is a figure which shows the expression level (relative value) of the adipogenin gene of an adipocyte when the egg yolk extract (IY) or egg yolk extract (OY) of a normal egg is added in a culture medium. ヨウ素高含有卵の卵黄抽出物（ＩＹ）又は普通卵の卵黄抽出物（ＯＹ）を培地中に添加した場合における、脂肪細胞のレプチン遺伝子の発現量（相対値）を示す図である。It is a figure which shows the expression level (relative value) of the leptin gene of an adipocyte when the egg yolk extract (IY) or egg yolk extract (OY) of a normal egg is added in a culture medium. ヨウ素高含有卵の卵黄抽出物（ＩＹ）又は普通卵の卵黄抽出物（ＯＹ）を培地中に添加した場合における、脂肪細胞のアディポネクチン遺伝子の発現量（相対値）を示す図である。It is a figure which shows the expression level (relative value) of the adiponectin gene of an adipocyte when the egg yolk extract (IY) or egg yolk extract (OY) of a normal egg is added in a culture medium.
　以下、本発明の実施形態について詳細に説明する。ただし、本発明は以下の実施形態に限定されるものではない。
　本明細書において「～」を用いて示された数値範囲は、「～」の前後に記載される数値をそれぞれ最小値及び最大値として含む範囲を示す。 Hereinafter, embodiments of the present invention will be described in detail. However, the present invention is not limited to the following embodiments.
In the present specification, a numerical range indicated by using “to” indicates a range including the numerical values described before and after “to” as the minimum value and the maximum value, respectively.
＜脂肪蓄積抑制剤、脂肪前駆細胞の分化抑制剤、内臓脂肪低減剤、及び内臓脂肪低減用飲食品＞
　第１実施形態の脂肪蓄積抑制剤、脂肪前駆細胞の分化抑制剤、内臓脂肪低減剤、及び内臓脂肪低減用飲食品は、いずれも、４．２質量ｐｐｍ以上のヨウ素を含有する鳥卵（以下、「ヨウ素高含有卵」ともいう。）を有効成分として含有する。 <Fat accumulation inhibitor, preadipocyte differentiation inhibitor, visceral fat reducing agent, and food and drink for reducing visceral fat>
The fat accumulation inhibitor, the precursor of preadipocytes, the visceral fat reducing agent, and the food and drink for reducing visceral fat according to the first embodiment are all eggs containing 4.2 ppm by mass or more of iodine (hereinafter referred to as “bird eggs”). , Also referred to as “iodine-rich egg”) as an active ingredient.
　鳥卵としては、鶏、鶉、烏骨鶏、アヒル等の鳥類の卵が挙げられ、鶏卵が好ましい。
　ヨウ素高含有卵は、ヨウ素源の配合によりヨウ素含有率を高めた飼料を鳥類に与え、卵中のヨウ素含有率を増加させることにより得ることができる。
　ヨウ素源としては、ヨウ素酸カルシウム、ヨウ素酸カリウム、ヨウ化カリウム、ヨウ素酸ナトリウム、ヨウ化チモール、ヨウ化銅、次ヨードサリチル酸、過ヨウ素酸カルシウム、カルシウムヨードビヘメイト等のヨウ素化合物；昆布、ケルプ等のヨウ素を高含有する海藻類又はその処理物などが挙げられる。鳥類の健康、ヨウ素の卵への移行率等の観点から、ヨウ素源としては、ヨウ素酸カルシウム、ヨウ素酸カリウム、及びヨウ化カリウムからなる群より選択される少なくとも１種を用いることが好ましい。また、ヨウ素酸カルシウム、ヨウ素酸カリウム、及びヨウ化カリウムからなる群より選択される少なくとも１種とともに、海藻類を併用することがより好ましい。 Examples of avian eggs include chicken eggs such as chickens, rabbits, rib chickens and ducks, with chicken eggs being preferred.
Eggs with high iodine content can be obtained by feeding birds with an increased iodine content by blending an iodine source and increasing the iodine content in the eggs.
Examples of iodine sources include iodine compounds such as calcium iodate, potassium iodate, potassium iodide, sodium iodate, thymol iodide, copper iodide, hypoiodosalicylic acid, calcium periodate, calcium iodobihemate; Examples include seaweeds containing a high content of iodine such as kelp or processed products thereof. From the viewpoint of bird health, the rate of migration of iodine to eggs, etc., it is preferable to use at least one selected from the group consisting of calcium iodate, potassium iodate, and potassium iodide as the iodine source. Moreover, it is more preferable to use a seaweed together with at least one selected from the group consisting of calcium iodate, potassium iodate, and potassium iodide.
　鳥類に与えるヨウ素量は、鳥類の種類によって適宜調整することができる。産卵鶏の場合には、例えば、１日につき１羽当たり５ｍｇ～２５０ｍｇのヨウ素摂取量とすることが好ましく、１日につき１羽当たり５ｍｇ～１５ｍｇのヨウ素摂取量とすることがより好ましい。産卵鶏が１日につき１羽当たり約１００ｇの飼料を摂取すると仮定した場合、飼料中のヨウ素含有率は、５０質量ｐｐｍ～２５００質量ｐｐｍとすることが好ましく、５０質量ｐｐｍ～１５０質量ｐｐｍとすることがより好ましい。 The amount of iodine given to birds can be adjusted as appropriate depending on the type of bird. In the case of laying hens, for example, the iodine intake is preferably 5 mg to 250 mg per bird per day, and more preferably 5 mg to 15 mg iodine per bird per day. Assuming that the laying hen ingests about 100 g of feed per bird per day, the iodine content in the feed is preferably 50 mass ppm to 2500 mass ppm, more preferably 50 mass ppm to 150 mass ppm. It is more preferable.
　ヨウ素を高含有する飼料を鳥類に与えると、約１週間後には目的とするヨウ素高含有卵が産出される。例えば、５０質量ｐｐｍ程度のヨウ素を含有する飼料を産卵鶏に与えると、１個当たり約３００μｇのヨウ素を含有する卵が産出される。 When a high-iodine feed is given to birds, the target high-iodine egg is produced after about one week. For example, when a feed containing about 50 ppm by mass of iodine is given to a laying hen, eggs containing about 300 μg of iodine per piece are produced.
　ヨウ素高含有卵のヨウ素含有率は、可食部全量に対して４．２質量ｐｐｍ以上であれば特に制限されず、例えば、４．２質量ｐｐｍ～２０．０質量ｐｐｍであることが好ましい。ヨウ素高含有卵のヨウ素含有率を２０．０質量ｐｐｍ以下とすることで、産卵率の低下が抑えられる傾向にある。市場で主に流通している殻付き鶏卵の可食部は１個当たり約４５ｇ～６６ｇであることから、４．２質量ｐｐｍ～２０．０質量ｐｐｍのヨウ素含有率は、１個当たり約２００μｇ～１４００μｇのヨウ素含有量に相当する。 The iodine content of the high-iodine egg is not particularly limited as long as it is 4.2 mass ppm or more with respect to the total amount of the edible portion, and is preferably 4.2 mass ppm to 20.0 mass ppm, for example. By setting the iodine content of the high-iodine egg to 20.0 mass ppm or less, a decrease in the egg-laying rate tends to be suppressed. Since the edible part of shell eggs circulated mainly in the market is about 45 to 66 g per piece, the iodine content of 4.2 to 20.0 ppm by weight is about 200 μg per piece. Corresponds to an iodine content of ˜1400 μg.
　なお、産卵鶏におけるヨウ素の要求量は飼料１ｋｇ当たり０．２ｍｇ（日本飼料標準家禽（２０１１年版）による）であり、実際の市販飼料中のヨウ素含有量は飼料１ｋｇ当たり０．３ｍｇ～２．０ｍｇとなっている。この市販飼料を用いて飼育された産卵鶏から産出される普通卵のヨウ素含有量は、１個当たり約９μｇ程度（日本食品標準成分表２０１５年版（七訂）による）であり、多くとも１個当たり約３０μｇ程度である。 The required amount of iodine in egg-laying hens is 0.2 mg per 1 kg of feed (according to Japanese feed standard poultry (2011 version)), and the actual iodine content in commercially available feed is 0.3 mg to 2.0 mg per 1 kg of feed. It has become. The iodine content of normal eggs produced from laying hens bred using this commercial feed is about 9 μg per piece (according to the Japanese Food Standards Ingredients 2015 edition (7th edition)), at most one piece. About 30 μg per unit.
　ヨウ素高含有卵は、市販品としても入手可能である。例えば、４．２質量ｐｐｍ以上のヨウ素を含有する鶏卵の市販品としては、日本農産工業（株）の「ヨード卵光」（「ヨード卵」は登録商標）が挙げられる。 ヨ ウ 素 Eggs with high iodine content are also available as commercial products. For example, as a commercial product of chicken eggs containing iodine of 4.2 mass ppm or more, “Iodo Egg Light” (“Iodo Egg” is a registered trademark) of Nippon Agricultural Industry Co., Ltd. can be mentioned.
　第１実施形態の脂肪蓄積抑制剤、脂肪前駆細胞の分化抑制剤、内臓脂肪低減剤、及び内臓脂肪低減用飲食品は、ヨウ素高含有卵の全卵を有効成分として含有していてもよい。また、ヨウ素高含有卵中のヨウ素の多くは、ペプチドと結合したヨウ化ペプチドとして卵黄中に含有されるため、第１実施形態の脂肪蓄積抑制剤、脂肪前駆細胞の分化抑制剤、内臓脂肪低減剤、及び内臓脂肪低減用飲食品は、ヨウ素高含有卵の卵黄を有効成分として含有していてもよく、卵黄抽出物を有効成分として含有していてもよい。卵黄抽出物は、卵黄中のヨウ化ペプチドを含有するものであれば特に制限されない。
　また、ヨウ素高含有卵の全卵、卵黄、及び卵黄抽出物は、必要に応じて、乾燥、濃縮、粉末化、顆粒化等の処理を施してもよい。 The fat accumulation inhibitor, the preadipocyte differentiation inhibitor, the visceral fat reducing agent, and the food and drink for reducing visceral fat according to the first embodiment may contain the whole egg of an iodine-rich egg as an active ingredient. Further, since most of iodine in the egg containing high iodine is contained in the yolk as an iodide peptide bound to the peptide, the fat accumulation inhibitor, the precursor of fat precursor cells, the visceral fat reduction according to the first embodiment. The agent and food and drink for reducing visceral fat may contain egg yolk of a high iodine content egg as an active ingredient, or may contain an egg yolk extract as an active ingredient. The egg yolk extract is not particularly limited as long as it contains an iodide peptide in egg yolk.
In addition, the whole egg, egg yolk, and egg yolk extract of the egg with high iodine content may be subjected to treatments such as drying, concentration, powdering, and granulating as necessary.
　第１実施形態の脂肪蓄積抑制剤、脂肪前駆細胞の分化抑制剤、及び内臓脂肪低減剤の剤形は特に制限されず、散剤、顆粒剤、錠剤、カプセル剤、シロップ剤、乳剤等が挙げられる。第１実施形態の脂肪蓄積抑制剤、脂肪前駆細胞の分化抑制剤、及び内臓脂肪低減剤は、剤形に応じて、各種の賦形剤、結合剤、崩壊剤、溶剤等をさらに含有していてもよい。 The dosage form of the fat accumulation inhibitor, the adipocyte differentiation inhibitor, and the visceral fat reducing agent of the first embodiment is not particularly limited, and examples thereof include powders, granules, tablets, capsules, syrups, and emulsions. . The fat accumulation inhibitor, the preadipocyte differentiation inhibitor, and the visceral fat-reducing agent of the first embodiment further contain various excipients, binders, disintegrants, solvents, and the like depending on the dosage form. May be.
　第１実施形態の脂肪蓄積抑制剤、脂肪前駆細胞の分化抑制剤、及び内臓脂肪低減剤の投与量及び投与期間、並びに第１実施形態の内臓脂肪低減用飲食品の摂取量及び摂取期間は、目的とする効果が奏される範囲であれば特に制限されない。一例としては、１日当たりのヨウ素量が３００μｇ以上となる投与量又は摂取量を１ヵ月間以上継続することが好ましく、３ヵ月間以上継続することがより好ましい。投与量又は摂取量の上限値は、ヨウ素の耐容上限量に基づいて設定することができる。一例としては、１日当たりのヨウ素量が３０００μｇ以下となる投与量又は摂取量とすることができる。 The dose and administration period of the fat accumulation inhibitor of the first embodiment, the differentiation inhibitor of preadipocytes, and the visceral fat reducing agent, and the intake and intake period of the food and drink for reducing visceral fat of the first embodiment are: There is no particular limitation as long as the intended effect is achieved. As an example, it is preferable to continue the dose or intake amount for which the iodine amount per day is 300 μg or more for 1 month or more, and it is more preferable to continue for 3 months or more. The upper limit of the dose or intake can be set based on the tolerable upper limit of iodine. As an example, the amount of iodine per day can be set to a dose or intake amount of 3000 μg or less.
　第１実施形態の脂肪蓄積抑制剤、脂肪前駆細胞の分化抑制剤、若しくは内臓脂肪低減剤を投与し、又は第１実施形態の内臓脂肪低減用飲食品を摂取することにより、肥満を予防又は改善することが可能である。すなわち、第１実施形態によれば、以下の方法もまた提供される。
（１）４．２質量ｐｐｍ以上のヨウ素を含有する鳥卵の有効量を対象者に投与することを含む脂肪蓄積抑制方法。
（２）４．２質量ｐｐｍ以上のヨウ素を含有する鳥卵の有効量を対象者に投与することを含む脂肪前駆細胞の分化抑制方法。
（３）４．２質量ｐｐｍ以上のヨウ素を含有する鳥卵の有効量を対象者に投与することを含む内臓脂肪低減方法。
（４）４．２質量ｐｐｍ以上のヨウ素を含有する鳥卵の有効量を摂取することを含む内臓脂肪低減方法。
（５）４．２質量ｐｐｍ以上のヨウ素を含有する鳥卵の有効量を対象者に投与することを含む肥満の予防又は改善方法。
（６）４．２質量ｐｐｍ以上のヨウ素を含有する鳥卵の有効量を摂取することを含む肥満の予防又は改善方法。 The obesity is prevented or improved by administering the fat accumulation inhibitor of the first embodiment, the differentiation inhibitor of preadipocytes, or the visceral fat reducing agent, or taking the food or drink for reducing visceral fat of the first embodiment. Is possible. That is, according to the first embodiment, the following method is also provided.
(1) A method for inhibiting fat accumulation, comprising administering an effective amount of a bird egg containing iodine of 4.2 mass ppm or more to a subject.
(2) A method for inhibiting differentiation of preadipocytes, comprising administering to a subject an effective amount of an egg containing 4.2 mass ppm or more of iodine.
(3) A visceral fat reduction method comprising administering to a subject an effective amount of an egg containing 4.2 ppm by mass or more of iodine.
(4) A visceral fat reduction method comprising ingesting an effective amount of an egg containing 4.2 ppm by mass or more of iodine.
(5) A method for preventing or improving obesity, comprising administering to a subject an effective amount of a bird egg containing iodine of 4.2 mass ppm or more.
(6) A method for preventing or improving obesity comprising ingesting an effective amount of a bird egg containing iodine of 4.2 mass ppm or more.
＜内臓脂肪低減剤＞
　第２実施形態の内臓脂肪低減剤は、ヨウ化ペプチドを含有する鳥卵の卵黄抽出物を有効成分とし、１日当たりのヨウ素量として３００μｇ以上投与されるように用いられる。 <Visceral fat reducing agent>
The visceral fat reducing agent according to the second embodiment is used so that egg yolk extract containing an iodinated peptide is an active ingredient and is administered in an amount of 300 μg or more per day.
　鳥卵としては、鶏、鶉、烏骨鶏、アヒル等の鳥類の卵が挙げられ、鶏卵が好ましい。鳥卵は、普通卵であっても上述したヨウ素高含有卵であってもよく、ヨウ素を高含有している点で上述したヨウ素高含有卵が好ましい。 Examples of the eggs include chicken eggs such as chickens, rabbits, rib chickens and ducks, and chicken eggs are preferred. The bird egg may be a normal egg or the above-described high-iodine egg, and the above-described high-iodine egg is preferable in terms of high iodine content.
　卵黄抽出物は、卵黄中のヨウ化ペプチドを含有するものであれば特に制限されない。卵黄抽出物は、必要に応じて、乾燥、濃縮、粉末化、顆粒化等の処理を施してもよい。 The egg yolk extract is not particularly limited as long as it contains an iodide peptide in egg yolk. The egg yolk extract may be subjected to treatments such as drying, concentration, pulverization, and granulation as necessary.
　第２実施形態の内臓脂肪低減剤の剤形は特に制限されず、散剤、顆粒剤、錠剤、カプセル剤、シロップ剤、乳剤等が挙げられる。第２実施形態の内臓脂肪低減剤は、剤形に応じて、各種の賦形剤、結合剤、崩壊剤、溶剤等をさらに含有していてもよい。 The dosage form of the visceral fat reducing agent of the second embodiment is not particularly limited, and examples thereof include powders, granules, tablets, capsules, syrups, and emulsions. The visceral fat reducing agent of the second embodiment may further contain various excipients, binders, disintegrants, solvents and the like depending on the dosage form.
　第２実施形態の内臓脂肪低減剤の投与量は、１日当たりのヨウ素量が３００μｇ以上となる投与量であれば特に制限されない。投与量の上限値は、ヨウ素の耐容上限量に基づいて設定することができる。一例としては、１日当たりのヨウ素量が３０００μｇ以下となる投与量とすることができる。
　第２実施形態の内臓脂肪低減剤の投与期間は、目的とする効果が奏される範囲であれば特に制限されない。一例としては、１ヵ月間以上継続して投与することが好ましく、３ヵ月間以上継続して投与することがより好ましい。 The dose of the visceral fat reducing agent according to the second embodiment is not particularly limited as long as the dose per day is 300 μg or more. The upper limit value of the dose can be set based on the tolerable upper limit amount of iodine. As an example, it can be set as the dosage which the iodine amount per day will be 3000 micrograms or less.
The administration period of the visceral fat reducing agent of the second embodiment is not particularly limited as long as the intended effect is exhibited. As an example, it is preferable to administer continuously for 1 month or more, and it is more preferable to administer continuously for 3 months or more.
　第２実施形態の内臓脂肪低減剤を投与することにより、肥満を予防又は改善することが可能である。すなわち、第２実施形態によれば、以下の方法もまた提供される。
（１）ヨウ化ペプチドを含有する鳥卵の卵黄抽出物を、１日当たりのヨウ素量として３００μｇ以上投与することを含む内臓脂肪低減方法。
（２）ヨウ化ペプチドを含有する鳥卵の卵黄抽出物を、１日当たりのヨウ素量として３００μｇ以上投与することを含む肥満の予防又は改善方法。 By administering the visceral fat reducing agent of the second embodiment, obesity can be prevented or ameliorated. That is, according to the second embodiment, the following method is also provided.
(1) A visceral fat reduction method comprising administering 300 μg or more of an egg yolk extract containing an iodinated peptide as an iodine amount per day.
(2) A method for preventing or improving obesity comprising administering 300 μg or more of an egg yolk extract containing an iodinated peptide as iodine amount per day.
　以下、実施例により本発明を具体的に説明するが、本発明は実施例に限定されるものではない。 Hereinafter, the present invention will be specifically described by way of examples, but the present invention is not limited to the examples.
［調製例１］
　可食部１００ｇ当たり約１３００μｇのヨウ素を含有する鶏卵（日本農産工業（株）、「ヨード卵光」）をヨウ素高含有卵として用い、卵黄のみを無菌状態で凍結乾燥（－１０℃、１８０分間）して卵粉を得た。得られた卵粉１ｇに対して５ｍＬの溶解バッファ（２０ｍＭ　Ｔｒｉｓ－ＨＣｌ（ｐＨ７．６）、５ｍＭ　ＤＴＴ（Dithiothreitol）、０．１ｗ／ｖ％　ＳＤＳ（Sodium Dodecyl Sulfate）、１ｖ／ｖ％　プロテアーゼ阻害剤カクテル）を加えて懸濁した後、１７０００Ｇで１５分間遠心分離を行った。得られた上清にＰＢＳ（Phosphate Buffered Saline）を加えてタンパク質濃度を１０μｇ／μＬに調整し、ヨウ素高含有卵の卵黄抽出物（ＩＹ）として用いた。なお、タンパク質濃度はＢｒａｄｆｏｒｄ法にて測定した。
　また、ヨウ素高含有卵の代わりに市販の鶏卵を用いたこと以外は上記と同様にして、普通卵の卵黄抽出物（ＯＹ）を調製した。 [Preparation Example 1]
Eggs containing about 1300 μg of iodine per 100 g of edible portion (Nippon Agricultural Industrial Co., Ltd., “Iodine egg light”) were used as eggs with high iodine content, and only egg yolk was lyophilized in a sterile condition (−10 ° C., 180 minutes) ) To obtain egg powder. 5 g of lysis buffer (20 mM Tris-HCl (pH 7.6), 5 mM DTT (Dithiothreitol), 0.1 w / v% SDS (Sodium Dodecyl Sulfate), 1 v / v% protease inhibitor) per 1 g of the obtained egg powder (Cocktail) was added and suspended, followed by centrifugation at 17000 G for 15 minutes. PBS (Phosphate Buffered Saline) was added to the obtained supernatant to adjust the protein concentration to 10 μg / μL, and the resulting mixture was used as an egg yolk extract (IY) of an iodine-rich egg. The protein concentration was measured by the Bradford method.
Moreover, the egg yolk extract (OY) of a normal egg was prepared like the above except having used the commercially available egg instead of the high iodine content egg.
［実験例１］
　実験例１では、マウス脂肪前駆細胞３Ｔ３－Ｌ１を脂肪細胞へと分化させ、脂肪細胞への脂肪蓄積量を測定した。３Ｔ３－Ｌ１細胞は、通常培養条件下においては線維芽細胞様の形態を示すが、コンフルエントな状態にした後にインスリン刺激を与えることによって、細胞内に脂肪粒を形成し、脂肪細胞へと分化する。 [Experimental Example 1]
In Experimental Example 1, mouse fat precursor cells 3T3-L1 were differentiated into adipocytes, and the amount of fat accumulated in the adipocytes was measured. 3T3-L1 cells usually show fibroblast-like morphology under culture conditions, but form insulin granules and differentiate into adipocytes by applying insulin stimulation after confluence. .
　まず、３Ｔ３－Ｌ１細胞を６ウェルプレートに播種し、コンフルエント２日後まで１０ｖ／ｖ％　ＦＢＳ（Fetal Bovine Serum）を含有するＤＭＥＭ（Dulbecco's Modified Eagle Medium）によって維持した。培地は４８時間毎に交換した。次いで、１０ｖ／ｖ％　ＦＢＳ、０．５ｍＭ　イソブチルメチルキサンチン、１μＭ　デキサメタゾン、及び１．７μＭ　インスリンを含有するＤＭＥＭに培地交換し、４８時間培養することにより、脂肪細胞への分化を誘導した。次いで、１０ｖ／ｖ％　ＦＢＳを含有するＤＭＥＭに培地交換した。さらに、ヨウ素高含有卵の卵黄抽出物（ＩＹ）又は普通卵の卵黄抽出物（ＯＹ）を５μｇ／ｍＬ、１０μｇ／ｍＬ、又は５０μｇ／ｍＬの終濃度となるように添加し、１０日間培養した。培地は４８時間毎に交換した。 First, 3T3-L1 cells were seeded in a 6-well plate and maintained by DMEM (Dulbecco's Modified Modified Eagle Medium) containing 10 v / v% FBS (Fetal Bovine Serum) until 2 days after confluence. The medium was changed every 48 hours. Next, the medium was changed to DMEM containing 10 v / v% FBS, 0.5 mM isobutylmethylxanthine, 1 μM dexamethasone, and 1.7 μM insulin, and differentiation into adipocytes was induced by culturing for 48 hours. Subsequently, the medium was replaced with DMEM containing 10 v / v% FBS. Furthermore, egg yolk extract (IY) containing high iodine content or egg yolk extract (OY) of normal egg was added to a final concentration of 5 μg / mL, 10 μg / mL, or 50 μg / mL, and cultured for 10 days. . The medium was changed every 48 hours.
　１０日間の培養後、分化した脂肪細胞をＰＢＳで３回洗浄し、１０ｖ／ｖ％　パラホルムアルデヒド溶液を用いて１０分間以上固定した。固定後、脂肪細胞をＰＢＳで２回洗浄し、３７℃条件下で０．５ｗ／ｖ％　Ｏｉｌ　Ｒｅｄ　Ｏ溶液（Sigma Aldrich社）を用いて染色した。その後、波長５７０ｎｍにおける吸光度を測定することにより、脂肪細胞への脂肪蓄積量を評価した。 After 10 days of culture, the differentiated adipocytes were washed 3 times with PBS and fixed with 10 v / v% paraformaldehyde solution for 10 minutes or more. After fixation, adipocytes were washed twice with PBS and stained with 0.5 w / v% Oil Red O solution (Sigma-Aldrich) at 37 ° C. Thereafter, the amount of fat accumulated in the fat cells was evaluated by measuring the absorbance at a wavelength of 570 nm.
　脂肪細胞への脂肪蓄積量の評価結果を図１に示す。図１は、脂肪細胞への脂肪蓄積量（相対値）を平均値±標準誤差で示したものである（いずれもｎ＝６）。図１に示すとおり、ヨウ素高含有卵の卵黄抽出物（ＩＹ）を５０μｇ／ｍＬの終濃度となるように培地中に添加した場合には、普通卵の卵黄抽出物（ＯＹ）を培地中に添加した場合と比較して、脂肪細胞への脂肪蓄積量が有意に低下した（ｐ＜０．０５）。 Fig. 1 shows the evaluation results of the amount of accumulated fat in fat cells. FIG. 1 shows the amount of accumulated fat (relative value) in fat cells as an average value ± standard error (n = 6 in all cases). As shown in FIG. 1, when egg yolk extract (IY) containing high iodine content is added to the medium so as to have a final concentration of 50 μg / mL, egg yolk extract (OY) of normal egg is added to the medium. Compared with the case where it added, the amount of fat accumulation in adipocytes was significantly reduced (p <0.05).
［実験例２］
　実験例２では、卵黄抽出物の代わりにヨウ化ナトリウムを用いること以外は実施例１と同様にして、脂肪細胞への脂肪蓄積量を測定した。なお、ヨウ化ナトリウムは、ヨウ化物イオンの終濃度が１０－９Ｍ、１０－８Ｍ、１０－７Ｍ、又は１０－６Ｍとなるように培地中に添加した。 [Experiment 2]
In Experimental Example 2, the amount of fat accumulated in fat cells was measured in the same manner as in Example 1 except that sodium iodide was used instead of the egg yolk extract. Sodium iodide was added to the medium so that the final concentration of iodide ions was 10 −9 M, 10 −8 M, 10 −7 M, or 10 −6 M.
　脂肪細胞への脂肪蓄積量の評価結果を図２に示す。図２に示すとおり、ヨウ化ナトリウムを培地中に添加しても、脂肪細胞への脂肪蓄積量は有意な変化を示さなかった。実験例１及び２の結果から、ヨウ素高含有卵の卵黄抽出物（ＩＹ）による脂肪蓄積抑制効果は、イオン状態のヨウ素ではなく、ヨウ素高含有卵に含有されるヨウ化ペプチドに起因するものであることが示唆される。 Fig. 2 shows the evaluation results of the amount of accumulated fat in fat cells. As shown in FIG. 2, even when sodium iodide was added to the medium, the amount of fat accumulated in the fat cells did not change significantly. From the results of Experimental Examples 1 and 2, the fat accumulation suppression effect by the egg yolk extract (IY) of the high iodine content egg is not due to iodine in an ionic state, but due to the iodide peptide contained in the high iodine content egg. It is suggested that there is.
［実験例３］
　実験例３では、３Ｔ３－Ｌ１細胞を脂肪細胞へと分化させ、ＧＰＤＨ活性を測定した。ＧＰＤＨは、脂肪合成に関与する酵素であり、また、脂肪前駆細胞から脂肪細胞への分化の指標ともなる。 [Experiment 3]
In Experimental Example 3, 3T3-L1 cells were differentiated into adipocytes, and GPDH activity was measured. GPDH is an enzyme involved in fat synthesis and also serves as an index of differentiation from preadipocytes into adipocytes.
　まず、実施例１と同様に、ヨウ素高含有卵の卵黄抽出物（ＩＹ）又は普通卵の卵黄抽出物（ＯＹ）を終濃度５０μｇ／ｍＬとなるように添加した培地を用いて、３Ｔ３－Ｌ１細胞を１０日間培養し、脂肪細胞を得た。１０日間の培養後の脂肪細胞（Ｄａｙ１０）をＰＢＳで洗浄し、細胞を破砕し、細胞破砕液についてＧＰＤＨ活性測定キット（（株）セルガレージ)を用いてＧＰＤＨ活性を測定した。得られた測定結果は、細胞破砕液中のタンパク質量で補正した。比較のため、１０日間の培養前の細胞（Ｄａｙ０）についても同様にしてＧＰＤＨ活性を測定した。 First, in the same manner as in Example 1, 3T3-L1 was prepared using a medium supplemented with egg yolk extract (IY) containing high iodine content or egg yolk extract (OY) of normal egg to a final concentration of 50 μg / mL. The cells were cultured for 10 days to obtain adipocytes. The adipocytes (Day 10) after 10 days of culturing were washed with PBS, the cells were crushed, and GPDH activity was measured for the cell lysate using a GPDH activity measurement kit (Cell Garage). The obtained measurement results were corrected with the amount of protein in the cell disruption solution. For comparison, GPDH activity was also measured in the same manner for cells (Day 0) before 10 days of culture.
　ＧＰＤＨ活性の測定結果を図３に示す。図３に示すとおり、ヨウ素高含有卵の卵黄抽出物（ＩＹ）を培地中に添加した場合には、普通卵の卵黄抽出物（ＯＹ）を培地中に添加した場合と比較して、ＧＰＤＨ活性が有意に低下した（ｐ＜０．０５）。 Fig. 3 shows the measurement results of GPDH activity. As shown in FIG. 3, when the egg yolk extract (IY) containing high iodine content was added to the medium, the GPDH activity was compared to the case where the egg yolk extract (OY) of normal egg was added to the medium. Significantly decreased (p <0.05).
［実験例４］
　実験例４では、３Ｔ３－Ｌ１細胞を脂肪細胞へと分化させ、脂肪前駆細胞から脂肪細胞への分化の指標となる遺伝子の発現量を測定した。 [Experimental Example 4]
In Experimental Example 4, 3T3-L1 cells were differentiated into adipocytes, and the expression level of a gene serving as an index for differentiation from preadipocytes into adipocytes was measured.
　まず、実施例１と同様に、ヨウ素高含有卵の卵黄抽出物（ＩＹ）又は普通卵の卵黄抽出物（ＯＹ）を終濃度５０μｇ／ｍＬとなるように添加した培地を用いて、３Ｔ３－Ｌ１細胞を１０日間培養し、脂肪細胞を得た。１０日間の培養後の脂肪細胞（Ｄａｙ１０）から全ＲＮＡを抽出し、常法に従ってリアルタイム逆転写ＰＣＲ（Polymerase Chain Reaction）により、ＰＰＡＲ－γ２、アディポゲニン、レプチン、及びアディポネクチンの各遺伝子の発現量を測定した。得られた測定結果は、内部標準であるβ－アクチン遺伝子の発現量で補正した。比較のため、１０日間の培養前の細胞（Ｄａｙ０）についても同様にして遺伝子の発現量を測定した。 First, in the same manner as in Example 1, 3T3-L1 was prepared using a medium supplemented with egg yolk extract (IY) containing high iodine content or egg yolk extract (OY) of normal egg to a final concentration of 50 μg / mL. The cells were cultured for 10 days to obtain adipocytes. Total RNA was extracted from adipocytes (Day 10) after 10 days of culture, and the expression level of each gene of PPAR-γ2, adipogenin, leptin, and adiponectin was measured by real-time reverse transcription PCR (Polymerase Chain に 従 っ て Reaction) according to a conventional method. did. The obtained measurement results were corrected with the expression level of β-actin gene as an internal standard. For comparison, the expression level of the gene was measured in the same manner for the cells (Day 0) before 10 days of culture.
　ＰＰＡＲ－γ２、アディポゲニン、レプチン、及びアディポネクチンの各遺伝子の発現量の測定結果（相対値）を図４Ａ～図４Ｄに示す。図４Ａ～図４Ｃにおける「ＮＤ」は不検出を意味する。図４Ａ～図４Ｄから分かるように、ヨウ素高含有卵の卵黄抽出物（ＩＹ）を培地中に添加した場合には、普通卵の卵黄抽出物（ＯＹ）を培地中に添加した場合と比較して、ＰＰＡＲ－γ２、アディポゲニン、レプチン、及びアディポネクチンの各遺伝子の発現量が有意に低下した（ＰＰＡＲ－γ２、アディポゲニン、及びレプチン：ｐ＜０．０５、アディポネクチン：ｐ＜０．１）。 4A to 4D show the measurement results (relative values) of the expression levels of each gene of PPAR-γ2, adipogenin, leptin, and adiponectin. “ND” in FIGS. 4A to 4C means no detection. As can be seen from FIGS. 4A to 4D, when the egg yolk extract (IY) containing high iodine content is added to the medium, it is compared with the case where the egg yolk extract (OY) of normal egg is added to the medium. Thus, the expression levels of the PPAR-γ2, adipogenin, leptin, and adiponectin genes were significantly reduced (PPAR-γ2, adipogenin, and leptin: p <0.05, adiponectin: p <0.1).
［実験例５］
　実験例５では、被験者を２群に分けてヨウ素高含有卵又は普通卵を継続的に摂取させ、体脂肪に対する影響をダブルブラインド法にて評価した。ヨウ素高含有卵としては、可食部１００ｇ当たり約１３００μｇのヨウ素を含有する鶏卵（日本農産工業（株）、「ヨード卵光」）を用いた。また、普通卵としては市販の鶏卵を用いた。 [Experimental Example 5]
In Experimental Example 5, the subjects were divided into two groups to continuously ingest iodine-rich eggs or normal eggs, and the effect on body fat was evaluated by the double blind method. Eggs containing about 1300 μg of iodine per 100 g of edible portion (Nippon Agricultural Industrial Co., Ltd., “Iodo Egg Light”) were used as eggs with high iodine content. In addition, commercially available eggs were used as normal eggs.
　４０歳以上６５歳未満かつＢＭＩ（Body Mass Index）が２５ｋｇ／ｍ２以上３０ｋｇ／ｍ２未満である男女５６名を被験者とし、試験群（男性：１４名、女性：１４名）と対照群（男性：１４名、女性：１４名）との２群に分けた。試験群については、１日当たり１個のヨウ素高含有卵をゆで卵として１２週間に亘って継続的に摂取させた。また、対照群については、１日当たり１個の普通卵をゆで卵として１２週間に亘って継続的に摂取させた。そして、腹部ＣＴ（Computed Tomography）画像を用いて体脂肪面積を測定するとともに、血液検査、尿検査等の各種検査を行い、試験前後で比較した。 The subjects were 56 men and women who were between 40 and 65 years old and had a BMI (Body Mass Index) of 25 kg / m 2 or more and less than 30 kg / m 2 , and the test group (male: 14 and female: 14) and the control group ( The group was divided into two groups: 14 males and 14 females. For the test group, one iodine-rich egg per day was continuously ingested as a boiled egg for 12 weeks. Moreover, about the control group, 1 normal egg per day was continuously ingested as a boiled egg over 12 weeks. And while measuring a body fat area using the abdominal CT (Computed Tomography) image, various tests, such as a blood test and a urine test, were performed and compared before and after the test.
　全体脂肪面積、内臓脂肪面積、及び皮下脂肪面積の試験前後における推移を表１に示す。また、表１には、血中の総コレステロール（Ｔ－ｃｈｏ）、トリグリセライド（ＴＧ）、ＬＤＬ（Low Density Lipoprotein）コレステロール（ＬＤＬ－ｃｈｏ）、ＨＤＬ（High Density Lipoprotein）コレステロール（ＨＤＬ－ｃｈｏ）、遊離トリヨードサイロニン（ＦＴ３）、及び遊離サイロキシン（ＦＴ４）の量の試験前後における推移についても併せて示す。表１は、各群について平均値±標準誤差で示したものである。 Table 1 shows changes in the total fat area, visceral fat area, and subcutaneous fat area before and after the test. Table 1 also shows blood total cholesterol (T-cho), triglyceride (TG), LDL (Low Density Lipoprotein) cholesterol (LDL-cho), HDL (High Density Lipoprotein) cholesterol (HDL-cho), free The transition of the amount of triiodothyronine (FT3) and free thyroxine (FT4) before and after the test is also shown. Table 1 shows the average value ± standard error for each group.
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
　表１に示すとおり、試験群では、全体脂肪面積及び内臓脂肪面積が試験前後で有意に低下したが（全体脂肪面積：ｐ＝０．０３７、内臓脂肪面積：ｐ＝０．００１）、皮下脂肪面積については有意な変化を示さなかった。一方、対照群では、全体脂肪面積、内臓脂肪面積、及び皮下脂肪面積のいずれも有意な変化を示さなかった。
　群間比較では、内臓脂肪面積の変化量及び変化率について試験群が有意に大きく（変化量：ｐ＝０．０４９、変化率：ｐ＝０．０３１）、群間差が認められた。 As shown in Table 1, in the test group, the total fat area and visceral fat area decreased significantly before and after the test (total fat area: p = 0.037, visceral fat area: p = 0.001), but subcutaneous fat. There was no significant change in area. On the other hand, in the control group, there was no significant change in any of the total fat area, visceral fat area, and subcutaneous fat area.
In comparison between groups, the test group was significantly larger in the amount of change and rate of change in visceral fat area (change amount: p = 0.049, change rate: p = 0.031), and differences between groups were observed.
　なお、脂質代謝に関連する血中の総コレステロール、トリグリセライド、ＬＤＬコレステロール、及びＨＤＬコレステロールの量は、試験群及び対照群のいずれも有意な変化を示さなかった。
　また、甲状腺機能に関連する血中の遊離トリヨードサイロニン（ＦＴ３）及び遊離サイロキシン（ＦＴ４）の量は、試験群及び対照群のいずれも有意な変化を示さず、正常範囲内で推移した。
　これらの結果から、ヨウ素高含有卵による内臓脂肪低減効果は、脂質代謝機能の向上又は甲状腺機能の向上に起因するものではなく、ヨウ素高含有卵に含有されるヨウ化ペプチドに起因するものであることが示唆される。 In addition, the amount of total cholesterol, triglyceride, LDL cholesterol, and HDL cholesterol in blood related to lipid metabolism did not change significantly in either the test group or the control group.
In addition, the amounts of free triiodothyronine (FT3) and free thyroxine (FT4) in blood related to thyroid function did not change significantly in either the test group or the control group, and remained within the normal range.
From these results, the visceral fat reduction effect by the iodine-rich egg is not due to the improvement of lipid metabolism function or thyroid function, but to the iodide peptide contained in the iodine-rich egg. It is suggested.
　本明細書に記載された全ての文献、特許出願、及び技術規格は、個々の文献、特許出願、及び技術規格が参照により取り込まれることが具体的かつ個々に記された場合と同程度に、本明細書中に参照により取り込まれる。 All documents, patent applications, and technical standards mentioned in this specification are to the same extent as if each individual document, patent application, and technical standard were specifically and individually stated to be incorporated by reference, Incorporated herein by reference.

Claims (5)

  1. 　４．２質量ｐｐｍ以上のヨウ素を含有する鳥卵を有効成分とする脂肪蓄積抑制剤。 A fat accumulation inhibitor comprising an egg containing 4.2 mass ppm or more of iodine as an active ingredient.
  2. 　４．２質量ｐｐｍ以上のヨウ素を含有する鳥卵を有効成分とする脂肪前駆細胞の分化抑制剤。 An agent for inhibiting differentiation of preadipocytes, which contains an egg containing an egg containing 4.2 mass ppm or more of iodine as an active ingredient.
  3. 　４．２質量ｐｐｍ以上のヨウ素を含有する鳥卵を有効成分とする内臓脂肪低減剤。 A visceral fat reducing agent containing as an active ingredient an egg containing 4.2 mass ppm or more of iodine.
  4. 　４．２質量ｐｐｍ以上のヨウ素を含有する鳥卵を有効成分とする内臓脂肪低減用飲食品。 4. Food and drink for reducing visceral fat, comprising as an active ingredient an egg containing iodine of 4.2 mass ppm or more.
  5. 　ヨウ化ペプチドを含有する鳥卵の卵黄抽出物を有効成分とし、１日当たりのヨウ素量として３００μｇ以上投与されるように用いられる内臓脂肪低減剤。 A visceral fat reducing agent used as an active ingredient an egg yolk extract containing an iodinated peptide and administered in an amount of iodine of 300 μg or more per day.
PCT/JP2016/077315 2016-09-15 2016-09-15 Fat accumulation inhibitor, preadipocyte differentiation inhibitor, visceral-fat-reducing agent, and food or beverage for visceral-fat reduction WO2018051471A1 (en)

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KR20230077612A (en) 2021-11-25 2023-06-01 (주)네오크레마 A new peptide that inhibits preadipocytes proliferation and differentiation into adipocyte and uses thereof
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