JP2008024647A - Adiponectin secretion promoting agent - Google Patents
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Abstract
Description
本発明はSUU型のトリグリセリドを有効成分とする、アディポネクチン分泌促進剤に関する。 The present invention relates to an adiponectin secretion promoter comprising SUU type triglyceride as an active ingredient.
わが国の食生活は近年大きく変化しており、肉類などの動物性食品の摂取が増加する一方で、日本食離れに伴う米類,野菜類,豆類等の植物性食品の摂取が減少している。このような背景において、糖尿病や動脈硬化疾患あるいは肥満症といった生活習慣病患者が増加してきている。 Japan's dietary habits have changed greatly in recent years, and the intake of animal foods such as meat has increased, while the intake of plant foods such as rice, vegetables, and beans accompanying the withdrawal from Japanese food has decreased. Against this background, patients with lifestyle-related diseases such as diabetes, arteriosclerosis and obesity are increasing.
ところで、生体の脂肪組織はエネルギーの単なる一時貯蔵庫ではなく、アディポサイトカイン(adipocytokines)と総称される種々の生理活性物質を分泌する「分泌組織」であると提唱されている(非特許文献1)。アディポサイトカインにはインスリン抵抗性に関与するTNF-αをはじめ、レプチン、高血圧との関連がうかがわれるアンジオテンシノーゲン、線溶系の重要な調節因子で血栓形成を促すPAI-1などがある。中でも近年最も注目されているのが「アディポネクチン」(adiponectin)である。アディポネクチンは、脂肪組織に特異的な分泌蛋白質であり、コラーゲン様の構造を有する。 By the way, it is proposed that the adipose tissue of a living body is not a mere temporary storage of energy but a “secretory tissue” that secretes various physiologically active substances collectively called adipocytokines (Non-patent Document 1). Adipocytokines include TNF-α, which is involved in insulin resistance, leptin, angiotensinogen, which is associated with hypertension, and PAI-1, which is an important regulator of the fibrinolytic system and promotes thrombus formation. Among them, “adiponectin” has attracted the most attention in recent years. Adiponectin is a secreted protein specific to adipose tissue and has a collagen-like structure.
アディポネクチンの生理作用の、重要な役割の一つとして、PAI-1、TNF-α、レジスチンや遊離脂肪酸の分泌を調節することによってインスリン抵抗性を改善することが示されている(非特許文献2,3)。マウスを用いた試験で、アディポネクチンはマクロファージを主体とする粥状動脈硬化巣局所に直接作用し、マクロファージの泡沫化および粥状動脈硬化を抑制することが報告されている(非特許文献4)。これらのことから、アディポネクチン濃度を積極的に高めることで、各疾病の予防が可能と想定される。 One of the important roles of adiponectin physiological action has been shown to improve insulin resistance by regulating the secretion of PAI-1, TNF-α, resistin and free fatty acids (Non-patent Document 2). , 3). In a test using mice, it has been reported that adiponectin acts directly on the area of the atherosclerotic lesion mainly composed of macrophages and suppresses foaming of macrophages and atherosclerosis (Non-patent Document 4). From these, it is assumed that each disease can be prevented by positively increasing the adiponectin concentration.
一方、長鎖飽和脂肪酸であるベヘン酸は、その高融点故に動物の消化管内での消化吸収率が低いことが知られている。この性質を用いた、ベヘン酸を構成脂肪酸として含有する、低吸収性のトリグリセリドが開示されている(特許文献1)。これらトリグリセリドは、通常の油脂の代替として使用することで、低カロリーな食品として用いることができるが、その効果についての認識はあくまで、摂取したベヘン酸が吸収されずに排泄される量に留まる上に、脂肪酸のグリセリンへの結合位置を特定したSUU型トリグリセリドについて、低濃度で用いた例は開示されていない。また、アディポネクチンの分泌については何ら示唆されていない。 On the other hand, behenic acid, which is a long-chain saturated fatty acid, is known to have a low digestive absorption rate in the digestive tract of animals due to its high melting point. A low-absorbency triglyceride containing behenic acid as a constituent fatty acid using this property has been disclosed (Patent Document 1). These triglycerides can be used as a low-calorie food when used as a substitute for normal fats and oils, but the recognition of the effect is limited to the amount of behenic acid ingested without being absorbed. In addition, there is no disclosure of an example of using SUU type triglycerides in which the binding position of fatty acid to glycerin is specified at a low concentration. There is no suggestion of adiponectin secretion.
かかる状況に鑑み、アディポネクチンの分泌をより強く促進しうる物質が解明できれば、アディポネクチンの血中濃度の上昇により、糖尿病や動脈硬化疾患の治療,予防薬剤や食品の開発が可能となる。すなわち、本発明は、アディポネクチンの分泌を促進しうる物質を見出し、このアディポネクチン分泌促進物質に基づく各種疾患の治療,予防に役立つ経口物を開発することを課題とする。 In view of this situation, if a substance capable of more strongly promoting the secretion of adiponectin can be elucidated, the increase in the blood concentration of adiponectin makes it possible to treat diabetes, arteriosclerotic diseases, develop preventive drugs and foods. That is, an object of the present invention is to find a substance capable of promoting the secretion of adiponectin and to develop an oral product useful for the treatment and prevention of various diseases based on this adiponectin secretion promoting substance.
本発明者らは上記課題を解決すべく、種々の成分の検討を行う中で、少量のSUU型のトリグリセリドの経口投与が血中アディポネクチン濃度を強く亢進することを初めて見出した。この知見に従ってSUU型のトリグリセリドをアディポネクチン分泌促進剤の有効成分として利用できることを見出し、本発明を完成させた。 In order to solve the above-mentioned problems, the present inventors have found for the first time that oral administration of a small amount of SUU type triglyceride strongly enhances blood adiponectin concentration. In accordance with this finding, it was found that SUU-type triglycerides can be used as an active ingredient of an adiponectin secretion promoter, and the present invention was completed.
すなわち、本発明は
(1)SUU型のトリグリセリドを有効成分とする、アディポネクチン分泌促進剤。但し式中、Sは炭素数20から24の飽和脂肪酸残基で、Uは炭素数16以上の不飽和脂肪酸残基である。
(2)Sがベヘン酸残基である(1)の分泌促進剤。
(3)Uがオレイン酸残基である(1)の分泌促進剤。
(4)SUU型のトリグリセリドを5から30重量%含有した油脂組成物である、(1)の分泌促進剤。
(5)アディポネクチン分泌促進効果に基づく健康表示を付した、(1)の分泌促進剤を含んだ食品。
である。
That is, the present invention is (1) an adiponectin secretion promoter comprising SUU type triglyceride as an active ingredient. In the formula, S is a saturated fatty acid residue having 20 to 24 carbon atoms, and U is an unsaturated fatty acid residue having 16 or more carbon atoms.
(2) The secretion promoter of (1), wherein S is a behenic acid residue.
(3) The secretion promoter of (1), wherein U is an oleic acid residue.
(4) The secretion promoter according to (1), which is an oil or fat composition containing 5 to 30% by weight of SUU type triglyceride.
(5) A food containing the secretion promoter of (1), with a health label based on the adiponectin secretion promoting effect.
It is.
本発明の提供する分泌促進剤は、アディポネクチンの分泌促進効果が高いため、それを利用した機能剤や飲食品を提供することができ、これらの経口摂取により血中アディポネクチン濃度を上昇させることができる。 Since the secretion enhancer provided by the present invention has a high secretion promoting effect of adiponectin, it can provide functional agents and foods and drinks using it, and can increase blood adiponectin concentration by oral intake of these. .
以下、本発明について詳細に説明する。本発明のアディポネクチン分泌促進剤は、SUU型のトリグリセリドを有効成分とすることが特徴である。本発明のSと示した脂肪酸残基は、炭素数20から24の飽和脂肪酸残基であるが、炭素数18以下の飽和脂肪酸では本効果が弱く、また炭素数26以上の飽和脂肪酸では、融点が上がり汎用性が減少する上に、脂肪酸の供給源も少なく実用性は高くない。効果と実現性から、炭素数22のベヘン酸が好ましい。 Hereinafter, the present invention will be described in detail. The adiponectin secretion promoter of the present invention is characterized by containing SUU-type triglyceride as an active ingredient. The fatty acid residue indicated as S in the present invention is a saturated fatty acid residue having 20 to 24 carbon atoms, but this effect is weak for saturated fatty acids having 18 or less carbon atoms, and for saturated fatty acids having 26 or more carbon atoms, the melting point In addition, the versatility is reduced, and there are few sources of fatty acids, so it is not practical. In view of the effect and feasibility, behenic acid having 22 carbon atoms is preferred.
Uと示した脂肪酸残基は、炭素数16以上の不飽和脂肪酸残基であるが、炭素数14以下の不飽和脂肪酸は、その供給源が少なく実用性は高くない。Uの炭素数の上限は特に設けないが、供給源を考えれば炭素数22以下が好ましく、炭素数18以下が最も好ましい。また不飽和度は特に制限は設けないが、脂肪酸の酸化安定性を考えれば、極端な多価不飽和脂肪酸は使用しにくく、ジエン酸以下の不飽和が好ましく、モノ不飽和酸が更に好ましく、オレイン酸が最も好ましい。 The fatty acid residue indicated as U is an unsaturated fatty acid residue having 16 or more carbon atoms, but unsaturated fatty acids having 14 or less carbon atoms are not highly practical because they have few sources. The upper limit of the carbon number of U is not particularly set, but considering the supply source, it is preferably 22 or less and most preferably 18 or less. The degree of unsaturation is not particularly limited, but considering the oxidative stability of fatty acids, extremely polyunsaturated fatty acids are difficult to use, preferably unsaturated below dienoic acid, more preferably monounsaturated acids, Oleic acid is most preferred.
そして本発明の有効成分は、Sで示した脂肪酸残基がグリセリンの1位または3位の水酸基、Uで示した脂肪酸残基がグリセリンの残り2つの水酸基にエステル結合した、SUU型で示される1長鎖飽和-2長鎖不飽和トリグリセリドである。尚、本発明明細書の表記では、脂肪酸のグリセリンへの結合位置について、その1位と3位とを区別しない。 The active ingredient of the present invention is represented by the SUU type in which the fatty acid residue represented by S is ester-bonded to the hydroxyl group at the 1- or 3-position of glycerol, and the fatty acid residue represented by U is ester-bonded to the remaining two hydroxyl groups of glycerol. 1 long chain saturated-2 long chain unsaturated triglyceride. In addition, in the notation of this invention specification, the 1st position and the 3rd position are not distinguished about the coupling | bonding position to the glycerol of a fatty acid.
本発明は、SUU型トリグリセリドを油脂中に少量含むことが特徴である。そしてこの経口摂取により、消化吸収性に大きな影響を及ぼすことなく、アディポネクチン分泌を促し、血中アディポネクチン濃度を上昇させることができる。アディポネクチン分泌促進剤としての有効摂取量は使用目的,使用対象,形態により異なるが、ベース油脂中に5から30重量%、好ましくは10から20重量%含むことで、血中アディポネクチン濃度を上昇させることができる。 The present invention is characterized by containing a small amount of SUU-type triglyceride in fats and oils. And by this ingestion, adiponectin secretion can be promoted and the blood adiponectin concentration can be increased without greatly affecting the digestibility. The effective intake as an adiponectin secretion enhancer varies depending on the purpose of use, the target of use, and the form, but by increasing the adiponectin concentration in the blood by containing 5 to 30% by weight, preferably 10 to 20% by weight in the base oil or fat Can do.
SUU型トリグリセリドが油脂中に30重量%を超えて存在すると、摂取カロリーの低下等の低消化吸収に起因する他の効果が表われる上に、脂溶性ビタミン類の吸収性阻害等の問題が発生し、更にSUU型トリグリセリドを含む油脂組成物の融点が上昇し汎用性に欠けるために、好ましくない。また油脂中に5重量%以下であると、血中アディポネクチン濃度上昇に関わる効果が明確に示されないため、不適切である。 When SUU-type triglycerides are present in oils and fats in excess of 30% by weight, other effects due to low digestion and absorption such as a decrease in calorie intake are exhibited, and problems such as absorption inhibition of fat-soluble vitamins occur. Furthermore, the melting point of the oil and fat composition containing SUU-type triglyceride is increased, and the versatility is lacking. Further, if it is 5% by weight or less in fats and oils, the effect relating to the increase in blood adiponectin concentration is not clearly shown, so that it is inappropriate.
本発明は、SUU型トリグリセリドを油脂中に少量含むことが特徴であるが、ベースとなる油脂は食用の動植物油脂、例えば、大豆油,ヒマワリ油,菜種油,キャノラ油,米糠油,紅花油,パーム油,パーム核油,ヤシ油,魚油,乳脂,カカオバター等であれば制限はない。多くの医薬品は、その適正量以上の摂取は安全性に問題を生じさせる可能性があるのに対し、本発明の有効成分は、天然の植物由来の含有物を使用したトリグリセリドであることから、安全性の観点からは摂取量の上限はほとんど問題にはされない。 The present invention is characterized by containing a small amount of SUU type triglyceride in fats and oils, but the base fats and oils are edible animal and vegetable fats and oils such as soybean oil, sunflower oil, rapeseed oil, canola oil, rice bran oil, safflower oil, palm Oil, palm kernel oil, coconut oil, fish oil, milk fat, cocoa butter, etc. are not limited. In many drugs, ingestion in excess of the proper amount may cause safety problems, whereas the active ingredient of the present invention is a triglyceride using natural plant-derived ingredients. From the viewpoint of safety, the upper limit of intake is hardly a problem.
本発明の有効成分であるSUU型のトリグリセリドは、ハイエルシン菜種油や魚油の極度硬化油を脂肪酸もしくはエステルにしたもの、または、更に蒸留により精製したものをS脂肪酸源として、一般的な不飽和脂肪酸を多く含む油脂、例えば、菜種油,キャノーラ油,大豆油,ひまわり油,サフラワー油,ハイオレインひまわり油,ハイオレインサフラワー油等をU脂肪酸源として、1,3位に特異性のあるリパーゼにより、エステル交換させることで得られる。得られた有効成分は溶剤分別により濃縮することも可能であり、好ましい。 The SUU type triglyceride which is an active ingredient of the present invention is a fatty acid or ester of a highly hardened oil of Hyelin rapeseed oil or fish oil, or further purified by distillation, using a general unsaturated fatty acid as a source of S fatty acid. By using a lipase having a specificity at positions 1 and 3 as a fatty acid source such as rapeseed oil, canola oil, soybean oil, sunflower oil, safflower oil, hyolein sunflower oil, hyolein safflower oil, etc. Obtained by transesterification. The obtained active ingredient can be concentrated by solvent fractionation, which is preferable.
本発明の分泌促進剤は、食品,薬剤又は飼料の、種々の用途に用いることができる。その際の形態は、ベースとなる油脂の融点や本発明のSUU型トリグリセリドの添加量によって異なるが、液油をそのまま用いる形態や、エマルジョンもしくはサスペンジョンなどの液剤の形態、クリーム,マーガリン,ショートニング,ハードバターなどの一般的な食品素材の形態などを採ることができる。この分泌促進剤を用いた食品には、油脂含量の比較的高い食品が好ましく、例えばマヨネーズ,ドレッシング類,各種のクリーム類,チョコレート等に配合できる。他には、焼き菓子等の菓子類、パン類などに配合することができるし、カプセル剤として用いることもできる。 The secretagogue of the present invention can be used for various uses of foods, drugs or feeds. The form at that time varies depending on the melting point of the base oil and fat and the addition amount of the SUU type triglyceride of the present invention, but the form in which the liquid oil is used as it is, the form of a liquid such as emulsion or suspension, cream, margarine, shortening, hard It can take the form of common food ingredients such as butter. The food using this secretagogue is preferably a food with a relatively high fat content, for example, mayonnaise, dressings, various creams, chocolate and the like. In addition, it can mix | blend with confectionery, such as baked confectionery, bread, etc., and can also be used as a capsule.
本発明の分泌促進剤およびこれを含む食品の摂取量の基準は特に設けるに及ばず、通常の食品や食品中の油脂組成物に代替して用いることで、アディポネクチン分泌促進効果を得ることができる。目標とすべき分泌促進剤の摂取量として、1日に5gから100g、好ましくは10gから50g程度が例示できる。 The standard for intake of the secretion promoter of the present invention and foods containing the same is not particularly set, and an adiponectin secretion promoting effect can be obtained by using it instead of normal foods and oil and fat compositions in foods. . Examples of the intake of the secretagogue to be targeted are 5 to 100 g, preferably 10 to 50 g per day.
以下、この発明の実施例を示すが、本発明がこれらによってその技術的範囲が限定されるものではない。なお、以下%は特に断りがない限り、重量%を示す。 Examples of the present invention will be described below, but the technical scope of the present invention is not limited by these examples. In the following, “%” means “% by weight” unless otherwise specified.
[製造例1]
炭素数22の不飽和脂肪酸を45%含む高エルシン菜種油の極度硬化油を加水分解し、エステル化して脂肪酸エチルエステルを得た。この脂肪酸エステルを精留し、アシル基の炭素原子数20から24の飽和脂肪酸エステルを97.9%含む留分を得た。この脂肪酸エステル留分70部を高オレイン酸ヒマワリ油30部と混合し、1,3位特異的な酵素剤を用いてエステル交換し、その後に脂肪酸エステルを留去することにより、沃素価45の反応油を得た。さらに分別して、低融点画分を収率42.4%で分取し、常法により精製した(試験油脂)。本試験油脂の融点は24℃、沃素価は55.8であり、その脂肪酸組成およびトリグリセリド(TG)組成を表1に示す。
[Production Example 1]
A highly hardened oil of high erucin rapeseed oil containing 45% of unsaturated fatty acids having 22 carbon atoms was hydrolyzed and esterified to obtain fatty acid ethyl ester. This fatty acid ester was rectified to obtain a fraction containing 97.9% of a saturated fatty acid ester having 20 to 24 carbon atoms in the acyl group. 70 parts of this fatty acid ester fraction was mixed with 30 parts of high oleic sunflower oil, transesterified using a 1,3-position specific enzyme agent, and then the fatty acid ester was distilled off to give an iodine value of 45. A reaction oil was obtained. Further fractionation was performed, and the low melting point fraction was collected at a yield of 42.4% and purified by a conventional method (test fat and oil). The test fats and oils have a melting point of 24 ° C. and an iodine value of 55.8. The fatty acid composition and triglyceride (TG) composition are shown in Table 1.
(表1)試験油脂の脂肪酸およびトリグリセリド組成
(Table 1) Fatty acid and triglyceride composition of test fats and oils
[試験例1]
試験油脂が血中アディポネクチン濃度に及ぼす影響について、動物実験により調査した。モデル動物は7週齢のSD系雄ラット(日本SLC(株)販売)を12匹を使用した。1週間の予備飼育後、群間の平均体重がほぼ同等になるように比較油脂群(6匹)と試験油脂群(6匹)に群分けを行った。食餌飼料はAIN-93G組成に基づき、油脂含量を28%とした。これらを6週間自由摂取させた。食餌配合は以下表2に示した。
[Test Example 1]
The effect of the test fats and oils on blood adiponectin concentration was investigated by animal experiments. Twelve 7-week-old SD male rats (sold by Japan SLC Co., Ltd.) were used as model animals. After one week of preliminary breeding, the group was divided into a comparative oil and fat group (6 animals) and a test oil and fat group (6 animals) so that the average body weights between groups were almost equal. The dietary feed was 28% fat based on the AIN-93G composition. These were ad libitum for 6 weeks. The diet composition is shown in Table 2 below.
(表2)試験食組成
(Table 2) Test meal composition
6週間後に腹部大動脈から採血を行った。常法に従って血漿を調製し、血液中のアディポネクチン量をELISA法キット(大塚製薬(株)製)にて測定した。結果を表3に示したように、SUU型のトリグリセリドの置き換えによって血中アディポネクチン濃度の上昇が認められた。一方、ラットの糞生成率は、8.0%(比較試験群)が9.4%(試験群)と微増したに過ぎず、本効果がベヘン酸の低吸収に起因するものではないと推定された。以上の結果より、SUU型のトリグリセリドがアディポネクチンの分泌促進作用を有していることが示された。 Six weeks later, blood was collected from the abdominal aorta. Plasma was prepared according to a conventional method, and the amount of adiponectin in the blood was measured with an ELISA method kit (manufactured by Otsuka Pharmaceutical Co., Ltd.). As shown in Table 3, an increase in blood adiponectin concentration was observed by replacement of SUU type triglyceride. On the other hand, the fecal production rate of rats was only slightly increased from 8.0% (comparison test group) to 9.4% (test group), and it was estimated that this effect was not caused by low absorption of behenic acid. From the above results, it was shown that SUU type triglyceride has an adiponectin secretion promoting action.
(表3)血中アディポネクチン濃度および糞生成率
(Table 3) Blood adiponectin concentration and fecal production rate
[実施例1]マヨネーズの製造
卵黄30部に食酢25部,食塩4部,グルタミン酸ナトリウム1部を加えて撹拌している中に、別途、製造例1で調製した試験油28部に菜種油112部を混合した混合油を徐々に加えることで、アディポネクチン分泌促進効果を持つマヨネーズが調製できる。
[Example 1] Production of mayonnaise While mixing 30 parts of egg yolk with 25 parts of vinegar, 4 parts of salt and 1 part of sodium glutamate, and separately stirring 28 parts of test oil prepared in Production Example 1, 112 parts of rapeseed oil The mayonnaise which has an adiponectin secretion promoting effect can be prepared by gradually adding the mixed oil mixed with.
[実施例2]クリームの製造
水51部に、脱脂粉乳4部,製造例1で調製した試験油9部,乳脂36部,シュガーエステル0.2部,レシチン0.2部,ヘキサメタリン酸ナトリウム0.1部から成る混合液を70℃に加温し、ホモミキサー(特殊機化工業株式会社製)で10,000回転で1分間撹拌し、予備乳化させる。次にこの液を高圧ホモゲナイザーを用い10kgf/cm2力下で均質化した後、144℃で4秒の加熱殺菌を行う。この溶液を急速に5℃まで冷却した後、5℃で一晩エージングすることでアディポネクチン分泌促進効果を持つクリームが調製できる。
[Example 2] Production of cream In 51 parts of water, 4 parts of skim milk powder, 9 parts of test oil prepared in Production Example 1, 36 parts of milk fat, 0.2 part of sugar ester, 0.2 part of lecithin, sodium hexametaphosphate 0 .1 part of the mixed solution is heated to 70 ° C., stirred with a homomixer (manufactured by Tokushu Kika Kogyo Co., Ltd.) at 10,000 rpm for 1 minute, and pre-emulsified. Next, this solution is homogenized using a high-pressure homogenizer under a force of 10 kgf / cm 2 and then sterilized by heating at 144 ° C. for 4 seconds. This solution is rapidly cooled to 5 ° C. and then aged at 5 ° C. overnight to prepare a cream having an adiponectin secretion promoting effect.
Claims (5)
A food comprising the secretion enhancer according to claim 1 with a health label based on an adiponectin secretion promoting effect.
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EP1983382A2 (en) | 2007-04-20 | 2008-10-22 | Ricoh Company, Ltd. | Image forming apparatus |
US9181561B2 (en) | 2009-01-29 | 2015-11-10 | Hokusan Co., Ltd. | Adiponectin-containing eating behavior control agent for oral administration |
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JP2008024648A (en) * | 2006-07-21 | 2008-02-07 | Fuji Oil Co Ltd | Hepatic lipid reducing agent |
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JP2006151875A (en) * | 2004-11-30 | 2006-06-15 | Fuji Oil Co Ltd | Lipase inhibitor |
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JP2008024648A (en) * | 2006-07-21 | 2008-02-07 | Fuji Oil Co Ltd | Hepatic lipid reducing agent |
EP1983382A2 (en) | 2007-04-20 | 2008-10-22 | Ricoh Company, Ltd. | Image forming apparatus |
US9181561B2 (en) | 2009-01-29 | 2015-11-10 | Hokusan Co., Ltd. | Adiponectin-containing eating behavior control agent for oral administration |
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