US20020015771A1 - Agent for increasing brown fat, comprising conjugated linoleic acid as active ingredient - Google Patents
Agent for increasing brown fat, comprising conjugated linoleic acid as active ingredient Download PDFInfo
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- US20020015771A1 US20020015771A1 US09/560,902 US56090200A US2002015771A1 US 20020015771 A1 US20020015771 A1 US 20020015771A1 US 56090200 A US56090200 A US 56090200A US 2002015771 A1 US2002015771 A1 US 2002015771A1
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- conjugated linoleic
- linoleic acid
- agent
- acid
- fat
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- 229940108924 conjugated linoleic acid Drugs 0.000 title claims abstract description 40
- 210000003486 adipose tissue brown Anatomy 0.000 title claims abstract description 31
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 title claims abstract description 25
- 230000001965 increasing effect Effects 0.000 title claims abstract description 18
- 239000003795 chemical substances by application Substances 0.000 title claims abstract description 15
- 239000004480 active ingredient Substances 0.000 title claims abstract description 8
- JBYXPOFIGCOSSB-GOJKSUSPSA-N 9-cis,11-trans-octadecadienoic acid Chemical compound CCCCCC\C=C\C=C/CCCCCCCC(O)=O JBYXPOFIGCOSSB-GOJKSUSPSA-N 0.000 title abstract 2
- JBYXPOFIGCOSSB-XBLVEGMJSA-N 9E,11E-octadecadienoic acid Chemical compound CCCCCC\C=C\C=C\CCCCCCCC(O)=O JBYXPOFIGCOSSB-XBLVEGMJSA-N 0.000 claims description 22
- 235000013305 food Nutrition 0.000 claims description 15
- 239000003921 oil Substances 0.000 claims description 10
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 8
- 239000000194 fatty acid Substances 0.000 claims description 8
- 229930195729 fatty acid Natural products 0.000 claims description 8
- 150000004665 fatty acids Chemical class 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 235000019485 Safflower oil Nutrition 0.000 claims description 6
- 239000003813 safflower oil Substances 0.000 claims description 6
- 235000005713 safflower oil Nutrition 0.000 claims description 6
- 239000003513 alkali Substances 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 230000021615 conjugation Effects 0.000 claims description 4
- 159000000007 calcium salts Chemical class 0.000 claims description 3
- GKJZMAHZJGSBKD-UHFFFAOYSA-N (10E,12E)-Octadeca-9,11-dienoic acid Natural products CCCCCC=CC=CCCCCCCCCC(O)=O GKJZMAHZJGSBKD-UHFFFAOYSA-N 0.000 claims description 2
- GKJZMAHZJGSBKD-BLHCBFLLSA-N (10e,12e)-octadeca-10,12-dienoic acid Chemical compound CCCCC\C=C\C=C\CCCCCCCCC(O)=O GKJZMAHZJGSBKD-BLHCBFLLSA-N 0.000 claims description 2
- GKJZMAHZJGSBKD-ANYPYVPJSA-N 10-trans-12-cis-linoleic acid Natural products CCCCCC=C\C=C\CCCCCCCCC(O)=O GKJZMAHZJGSBKD-ANYPYVPJSA-N 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims description 2
- 159000000000 sodium salts Chemical class 0.000 claims description 2
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 claims 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims 1
- 210000000577 adipose tissue Anatomy 0.000 description 10
- 208000008589 Obesity Diseases 0.000 description 9
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- 239000003925 fat Substances 0.000 description 6
- 235000019197 fats Nutrition 0.000 description 6
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 5
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 4
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- 235000020778 linoleic acid Nutrition 0.000 description 4
- 239000000825 pharmaceutical preparation Substances 0.000 description 4
- 230000004584 weight gain Effects 0.000 description 4
- 235000019786 weight gain Nutrition 0.000 description 4
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- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
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- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
- 102000002666 Carnitine O-palmitoyltransferase Human genes 0.000 description 2
- 108010018424 Carnitine O-palmitoyltransferase Proteins 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 239000005642 Oleic acid Substances 0.000 description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
- 235000021314 Palmitic acid Nutrition 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 229940099112 cornstarch Drugs 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
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- 230000002708 enhancing effect Effects 0.000 description 2
- 235000012631 food intake Nutrition 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 150000003626 triacylglycerols Chemical class 0.000 description 2
- QWJSAWXRUVVRLH-LREBCSMRSA-M 2-hydroxyethyl(trimethyl)azanium;(2r,3r)-2,3,4-trihydroxy-4-oxobutanoate Chemical compound C[N+](C)(C)CCO.OC(=O)[C@H](O)[C@@H](O)C([O-])=O QWJSAWXRUVVRLH-LREBCSMRSA-M 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 206010059245 Angiopathy Diseases 0.000 description 1
- 101710095342 Apolipoprotein B Proteins 0.000 description 1
- 102100040202 Apolipoprotein B-100 Human genes 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 206010020710 Hyperphagia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 150000000996 L-ascorbic acids Chemical class 0.000 description 1
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 1
- 235000019393 L-cystine Nutrition 0.000 description 1
- 239000004158 L-cystine Substances 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical class C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- BGNXCDMCOKJUMV-UHFFFAOYSA-N Tert-Butylhydroquinone Chemical compound CC(C)(C)C1=CC(O)=CC=C1O BGNXCDMCOKJUMV-UHFFFAOYSA-N 0.000 description 1
- 241000030538 Thecla Species 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 235000020661 alpha-linolenic acid Nutrition 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 239000003005 anticarcinogenic agent Substances 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 210000001099 axilla Anatomy 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000001593 brown adipocyte Anatomy 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229960003067 cystine Drugs 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 201000010063 epididymitis Diseases 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229960004488 linolenic acid Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 235000021313 oleic acid Nutrition 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 210000002820 sympathetic nervous system Anatomy 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11C—FATTY ACIDS FROM FATS, OILS OR WAXES; CANDLES; FATS, OILS OR FATTY ACIDS BY CHEMICAL MODIFICATION OF FATS, OILS, OR FATTY ACIDS OBTAINED THEREFROM
- C11C3/00—Fats, oils, or fatty acids by chemical modification of fats, oils, or fatty acids obtained therefrom
- C11C3/14—Fats, oils, or fatty acids by chemical modification of fats, oils, or fatty acids obtained therefrom by isomerisation
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/158—Fatty acids; Fats; Products containing oils or fats
-
- 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
- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
- A23L33/12—Fatty acids or derivatives thereof
-
- 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
- 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
Definitions
- the present invention relates to an agent for increasing brown fat, comprising a conjugated linoleic acid as an active ingredient. More particularly, the present invention relates to an agent for increasing brown fat, comprising a conjugated linoleic acid as an active ingredient, which agent can increase brown fat cells capable of consuming extra energy and producing heat to prevent obesity, and use of the agent in the field of foods.
- Fat is stored in adipose tissues.
- Adipose tissues are classified into two types which are utterly different from each other in function.
- One of the adipose tissues is a white adipose tissue which occupies the major part of the adipose tissues and functions to accumulate extra energy
- the other adipose tissue is a brown adipose tissue which has a function opposite to that of the white adipose tissue, that is, functions to consume extra energy.
- the brown adipose tissue is significantly found in infancy, and the level thereof decreases with aging.
- the brown adipose tissue is present in the back of the neck, a portion around shoulder blade in the back, axilla, periphery of the heart, and periphery of the kidney, and the total weight thereof is as small as about 40 g.
- This brown adipose tissue is governed by a sympathetic nervous system, and functions to generate heat for body temperature retention purposes and, in addition, to burn extra energy, thereby preventing obesity.
- Increasing and developing this brown adipose tissue are a great aid in eliminating obesity and are expected to prevent or reduce obesity.
- conjugated linoleic acids are isolated from fried meats (Y. L. Ha et al., Carcinogenesis, 8, 1881-1887, 1987), and, up to now, the following reports have been made on various activities of the conjugated linoleic acids: ⁇ circle over (1) ⁇ anti-carcinogens (Cancer Research, 51, 6118-6124, 1991); ⁇ circle over (2) ⁇ method for enhancing animal feed efficiency (Japanese Patent No. 2745245); ⁇ circle over (3) ⁇ method for storing foods and a preservative for use therein (Japanese Patent No.
- an agent for increasing brown fat comprising a conjugated linoleic acid as an active ingredient.
- Conjugated linoleic acids (CLA) usable in the present invention include 9,11-octadecadienoic acid, 10,12-octadecadienoic acid, and mixtures of said compounds. Among others, 9c,11t/9t, 11c-octadecadienoic acid is preferred.
- Forms of the conjugated linoleic acid usable herein include fatty acids, mono-, di-, or triglycerides, sodium salts, potassium salts, calcium salts, phospholipids, and lysophospholipids, and a mixture of two or more of them. Among them, fatty acids, triglycerides, phospholipids, and calcium salts are preferred. Further, derivatives of conjugated linoleic acids, for example, ascorbic acid derivatives and mitomycin C derivatives, may also be used.
- the “agent for increasing brown fat, comprising a conjugated linoleic acid as an active ingredient” according to the present invention may be used as pharmaceutical preparations and, in addition, as antiobesitic foods.
- One of embodiments of the antiobesitic food is a conjugated linoleic acid-containing fat-and-oil product obtained by subjecting a linoleic acid-containing fat and oil (for example, a safflower oil) to an alkali conjugation reaction to convert linoleic acid in the fat and oil to conjugated linoleic acid.
- the “alkali conjugation reaction” is a reaction such that a fatty acid is converted to a conjugated fatty acid by isomerization of the fatty acid in an alkali-organic solvent solution.
- potassium hydroxide is used as the alkali
- ethylene glycol is used as the organic solvent (J. Am.
- the content of CLA in a conjugated linoleic acid-containing fat and oil obtained by the above alkali conjugation method is generally 10 to 95%, preferably 50 to 80%, with the balance comprising palmitic acid, stearic acid, oleic acid, unconjugated linoleic acids, etc.
- the conjugated linoleic acid may be used in combination with other ingredients, for example, medicinal diluents (lactose, starch, dextrin, gum arabic or the like).
- the agent for increasing brown fat may be used in the form of tablets, capsules, or liquids.
- the content of the conjugated linoleic acid in the food or feed is generally 0.001 to 100% by weight, preferably 0.01 to 80% by weight.
- the intake of the conjugated linoleic acid is generally 0.01 to 3% by weight, preferably 0.05 to 1% by weight, based on the weight of diet.
- Sprague-Dawley male rats of four weeks of age were pre-bred, and then divided into two groups (each group consisting of 8 rats), a 1.0% linoleic acid group (a control group) and a 1.0% CLA group.
- the experimental diet shown in Table 1 and water were then freely fed to these two groups of rats.
- the CLA used was composed mainly of two types, 9c,11t/9t,11c-18:2 and 10t,12c-18:2.
- the 8 rats constituting each group were sacrificed, and the organs were taken out.
- CPT carnitine palmitoyltransferase
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- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Polymers & Plastics (AREA)
- Health & Medical Sciences (AREA)
- Food Science & Technology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Nutrition Science (AREA)
- Wood Science & Technology (AREA)
- Mycology (AREA)
- Animal Husbandry (AREA)
- Obesity (AREA)
- Child & Adolescent Psychology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Diabetes (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Fodder In General (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Edible Oils And Fats (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Feed For Specific Animals (AREA)
Abstract
Description
- 1. Field of the Invention
- The present invention relates to an agent for increasing brown fat, comprising a conjugated linoleic acid as an active ingredient. More particularly, the present invention relates to an agent for increasing brown fat, comprising a conjugated linoleic acid as an active ingredient, which agent can increase brown fat cells capable of consuming extra energy and producing heat to prevent obesity, and use of the agent in the field of foods.
- 2. Background Art
- In recent years, patients suffering from obesity have been increased also in Japan, and this is becoming a serious social problem. Obesity derived from such factors as increased ingestion (hyperphagia), reduced excercise (lack of excercise), and a fluctuation in generation of body heat causes accumulation of a large amount of body fat. This is causative of arteriosclerosis, hypertension, diabetes, and cardiac diseases, and, in some cases, leads to complications, such as angiopathy, neuropathy, and aphylaxis.
- Fat is stored in adipose tissues. Adipose tissues are classified into two types which are utterly different from each other in function. One of the adipose tissues is a white adipose tissue which occupies the major part of the adipose tissues and functions to accumulate extra energy, and the other adipose tissue is a brown adipose tissue which has a function opposite to that of the white adipose tissue, that is, functions to consume extra energy. The brown adipose tissue is significantly found in infancy, and the level thereof decreases with aging. The brown adipose tissue is present in the back of the neck, a portion around shoulder blade in the back, axilla, periphery of the heart, and periphery of the kidney, and the total weight thereof is as small as about 40 g. This brown adipose tissue is governed by a sympathetic nervous system, and functions to generate heat for body temperature retention purposes and, in addition, to burn extra energy, thereby preventing obesity. Increasing and developing this brown adipose tissue are a great aid in eliminating obesity and are expected to prevent or reduce obesity.
- On the other hand, conjugated linoleic acids are isolated from fried meats (Y. L. Ha et al., Carcinogenesis, 8, 1881-1887, 1987), and, up to now, the following reports have been made on various activities of the conjugated linoleic acids: {circle over (1)} anti-carcinogens (Cancer Research, 51, 6118-6124, 1991); {circle over (2)} method for enhancing animal feed efficiency (Japanese Patent No. 2745245); {circle over (3)} method for storing foods and a preservative for use therein (Japanese Patent No. 1935402); {circle over (4)} methods for preventing weight loss, reduction in weight gain, and anorexia due to immune stimulation (U.S. Pat. No. 5,430,066); {circle over (5)}0 method for reducing body fat (U.S. Pat. No. 5,554,646); {circle over (6)} methods for maintaining and enhancing bone mineral content (U.S. Pat. No. 5,804,210); and {circle over (7)} method for reducing secretion of apolipoprotein B (U.S. Pat. No. 5,837,733). So far as the present inventors know, however, there is no report such that the conjugated linoleic acids act to increase brown fat.
- Accordingly, it is an object of the present invention to provide pharmaceutical preparations, foods, and feed which can increase and develop brown adipose tissues to prevent and remedy obesity.
- The present inventors have repeated extensive and intensive studies using brown adipose tissues as an index of the usefulness in prophylaxis and therapy of obesity and, as a result, have found that conjugated linoleic acids have high activity to increase brown fat and thus are useful for the prophylaxis of obesity. This has led to the completion of the present invention.
- Thus, according to the present invention, there is provided an agent for increasing brown fat, comprising a conjugated linoleic acid as an active ingredient.
- Conjugated linoleic acids (CLA) usable in the present invention include 9,11-octadecadienoic acid, 10,12-octadecadienoic acid, and mixtures of said compounds. Among others, 9c,11t/9t, 11c-octadecadienoic acid is preferred.
- Forms of the conjugated linoleic acid usable herein include fatty acids, mono-, di-, or triglycerides, sodium salts, potassium salts, calcium salts, phospholipids, and lysophospholipids, and a mixture of two or more of them. Among them, fatty acids, triglycerides, phospholipids, and calcium salts are preferred. Further, derivatives of conjugated linoleic acids, for example, ascorbic acid derivatives and mitomycin C derivatives, may also be used.
- The “agent for increasing brown fat, comprising a conjugated linoleic acid as an active ingredient” according to the present invention may be used as pharmaceutical preparations and, in addition, as antiobesitic foods.
- One of embodiments of the antiobesitic food is a conjugated linoleic acid-containing fat-and-oil product obtained by subjecting a linoleic acid-containing fat and oil (for example, a safflower oil) to an alkali conjugation reaction to convert linoleic acid in the fat and oil to conjugated linoleic acid. The “alkali conjugation reaction” is a reaction such that a fatty acid is converted to a conjugated fatty acid by isomerization of the fatty acid in an alkali-organic solvent solution. In a conventional representative method used to this end, potassium hydroxide is used as the alkali, and ethylene glycol is used as the organic solvent (J. Am. Oil Chem. Soc., 36, 631, (1959) and Standard Methods for the Analysis of Oils, Fats and Derivatives 2.4.16-17, Abstract of the 34th Annual Meeting of Japan Oil Chemists' Society, p. 171 (1995)). Further, the present inventors have previously proposed a process for producing conjugated linoleic acid with improved conversion wherein propylene glycol is used as an organic solvent (Japanese Patent Application No. 288094/1996). When the starting fat and oil is a safflower oil, the content of CLA in a conjugated linoleic acid-containing fat and oil obtained by the above alkali conjugation method is generally 10 to 95%, preferably 50 to 80%, with the balance comprising palmitic acid, stearic acid, oleic acid, unconjugated linoleic acids, etc.
- When the “agent for increasing brown fat, comprising a conjugated linoleic acid as an active ingredient” according to the present invention is used as pharmaceutical preparations, the conjugated linoleic acid may be used in combination with other ingredients, for example, medicinal diluents (lactose, starch, dextrin, gum arabic or the like). The agent for increasing brown fat may be used in the form of tablets, capsules, or liquids.
- When the agent for increasing brown fat according to the present invention is used as foods or feeds, the content of the conjugated linoleic acid in the food or feed is generally 0.001 to 100% by weight, preferably 0.01 to 80% by weight.
- In any of the use of the agent for increasing brown fat according to the present invention in foods, pharmaceutical preparations, feeds, and pet foods, the intake of the conjugated linoleic acid is generally 0.01 to 3% by weight, preferably 0.05 to 1% by weight, based on the weight of diet.
- The following experimental example demonstrates that conjugated linoleic acid can increase the weight of brown adipose tissues.
- Sprague-Dawley male rats of four weeks of age were pre-bred, and then divided into two groups (each group consisting of 8 rats), a 1.0% linoleic acid group (a control group) and a 1.0% CLA group. The experimental diet shown in Table 1 and water were then freely fed to these two groups of rats. As shown in Table 2, the CLA used was composed mainly of two types, 9c,11t/9t,11c-18:2 and 10t,12c-18:2. Four weeks after the initiation of feeding, the 8 rats constituting each group were sacrificed, and the organs were taken out.
- As a result, there was no significant difference in intake and weight gain between the two groups.
- Further, as shown in Table 3, there was no difference in the weight of tissues of liver, kidney, heart, lungs, spleen, and brain between the two groups. On the other hand, for the CLA-supplemented group, as compared with the control group, the weight of adipose tissues around the kidney, which are white adipose tissues, was significantly decreased, and the weight of brown adipose tissues in the back was significantly increased.
- Further, the activity of carnitine palmitoyltransferase (CPT) as a rate-determining enzyme in β-oxidation of fatty acids was measured in brown adipose tissues. As shown in Table 4, the activity for the CLA-supplemented group was higher than that for the control group.
- The above results show that feeding of CLA to rats can increase brown adipose tissues and can enhance carnitine palmitoyltransferase (CPT) activity without affecting the food intake and weight gain of rats. Therefore, CLA can be expected to consume extra energy and to generate heat, thereby exhibiting antiobesitic effect which is free from side effect and harmless to the human body.
TABLE 1 Composition of feed (AIN-93G) Experimental groups Control group CLA Ingredients (g/100 g) Casein 20.0 20.0 Soybean oil 6.0 6.0 α-Cornstarch 13.2 13.2 Sucrose 10.0 10.0 Mineral mix (AIN-93G) 3.5 3.5 Vitamin mix (AIN-93VX) 1.0 1.0 L-Cystine 0.3 0.3 Choline tartrate 0.25 0.25 Cellulose 5.0 5.0 t-Butylhydroquinone 0.0014 0.0014 Cornstarch 39.7 39.7 LA (safflower oil) 1.0 — CLA — 1.0 -
TABLE 2 CLA and fatty acid composition of safflower oil CLA Safflower oil C16: 0 (palmitic acid ) 6.9 6.7 C18: 0 (stearic acid) 2.4 2.4 C18: 1 (oleic acid) 15.3 15.1 C18: 2 (linoleic acid) 0.7 74.1 CLA (conjugated linoleic acid) 74.1 n.d. c9, t11/t9, c11-18:2 (34.1) — t10, c12-18:2 (35.9) — c9, c11/c10, c12-18:2 (2.5) — t9, t11/c10, t12-18:2 (1.6) — C18: 3 (α-linolenic acid) — 0.5 Others 0.6 1.2 -
TABLE 3 Growth and weight of organs of rats Experimental groups Parameter Control group CLA Weight gain, g/4 weeks 217 227 Food intake, g/day 21.0 21.0 Weight of organs, g/100 g body weight Liver 4.36 4.40 Kidney 0.75 0.78 Heart 0.39 0.36 Lung 0.42 0.40 Spleen 0.22 0.22 Brain 0.40 0.38 Peri-renal adipose tissue 1.72 1.16 Epididymal adipose tissue 1.13 1.17 Brown adipose tissue 0.15 0.21 -
TABLE 4 Activity of carnitine-palmitin transferase (CPT) in brown adipose tissue Experimental groups Parameter Control group CLA CPT activity, 192.5 239.1 μmol/min/total BAT (brown adipose tissue)
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EP1174416A1 (en) * | 1999-04-27 | 2002-01-23 | Kabushiki Kaisha Yakult Honsha | Conjugated fatty acid esters |
WO2002094027A1 (en) * | 2001-05-21 | 2002-11-28 | Nestec, Ltd. | Inhibition of $i(tyrophagus putrescentiae) in pet food products |
US20100150885A1 (en) * | 2005-06-01 | 2010-06-17 | Joslin Diabetes Center, Inc. | Methods and compositions for inducing brown adipogenesis |
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Cited By (8)
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EP1174416A1 (en) * | 1999-04-27 | 2002-01-23 | Kabushiki Kaisha Yakult Honsha | Conjugated fatty acid esters |
EP1174416A4 (en) * | 1999-04-27 | 2002-09-25 | Yakult Honsha Kk | Conjugated fatty acid esters |
WO2002094027A1 (en) * | 2001-05-21 | 2002-11-28 | Nestec, Ltd. | Inhibition of $i(tyrophagus putrescentiae) in pet food products |
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US20100150885A1 (en) * | 2005-06-01 | 2010-06-17 | Joslin Diabetes Center, Inc. | Methods and compositions for inducing brown adipogenesis |
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CN115245510A (en) * | 2021-04-28 | 2022-10-28 | 扬州大学 | Application of trans-10, cis-12 conjugated linoleic acid |
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