JP4448211B2 - Uncoupling protein expression inducer - Google Patents
Uncoupling protein expression inducer Download PDFInfo
- Publication number
- JP4448211B2 JP4448211B2 JP23997199A JP23997199A JP4448211B2 JP 4448211 B2 JP4448211 B2 JP 4448211B2 JP 23997199 A JP23997199 A JP 23997199A JP 23997199 A JP23997199 A JP 23997199A JP 4448211 B2 JP4448211 B2 JP 4448211B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- ucp
- diacylglycerol
- expression inducer
- protein expression
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Description
【0001】
【発明の属する技術分野】
本発明は、脱共役蛋白質の発現誘導剤に関する。
【0002】
【従来の技術及び発明が解決しようとする課題】
脱共役とは、生体内の酸化的リン酸化において、電子伝達で得られたエネルギーがATP合成反応に共役することを阻害することをいい、ATP合成に共役される化学エネルギーを熱エネルギーに変換する点で重要な生体機能の1つである。かかる脱共役機能の重要性から、多くの脱共役剤が見出されており、生体内に存在する物質としては、例えばミトコンドリアに存在する脱共役蛋白質(以下、「UCP」という)が知られている。
【0003】
かかるUCPの発現を誘導することができれば、 ATP合成に共役される化学エネルギーの熱エネルギーへの変換効率が向上すると考えられるが、これまでUCP発現誘導剤はほとんど知られておらず、その開発が求められていた。
【0004】
【課題を解決するための手段】
本発明者は、各種の脂質及び薬剤について、UCPの発現誘導効果について検討を行った結果、意外にも、ジアシルグリセロールが、優れたUCP発現誘導効果を有することを見出し、本発明を完成した。
【0005】
本発明は、ジアシルグリセロールを有効成分とする脱共役蛋白質発現誘導剤を提供する。
【0006】
【発明の実施の形態】
本発明においてジアシルグリセロールを構成するアシル基は、炭素数8〜24、特に16〜22の飽和又は不飽和のアシル基が好ましい。不飽和結合の位置、その数に特に制限はないが、モノエン長鎖アシル基、ω3系長鎖不飽和アシル基(不飽和結合の位置をω位から特定し、ω位から3番目の炭素原子に最初の不飽和結合が位置する長鎖不飽和アシル基)、 ω6系長鎖不飽和アシル基(不飽和結合の位置をω位から特定し、ω位から6番目の炭素原子に最初の不飽和結合が位置する長鎖不飽和アシル基)が好ましく、モノエン長鎖アシル基としては、ヘキサデカモノエノイル基、オクタデカモノエノイル基、エイコサデカモノエノイル基、ドコサデカモノエノイル基が特に好ましく、ω3系長鎖不飽和アシル基としては、α−リノレノイル基(allcis−9,12,15−オクタデカトリエノイル基)、エイコサペンタエノイル基、ドコサヘキサエノイル基が特に好ましく、ω6系長鎖不飽和アシル基としては、γ−リノレノイル基(allcis−6,9,12−オクタデカトリエノイル基)、リノレイル基(c,c−9,12−オクタデカジエノイル基)、アラキドイル基(allcis−5,8,11,14−エイコサテトラエノイル基)が特に好ましい。また不飽和のアシル基の量は、全アシル基の55重量%(以下、単に「%」で示す。)以上が好ましく、70%以上がより好ましく、90%以上が特に好ましい。
【0007】
かかるジアシルグリセロールは、グリセリンと、飽和又は不飽和脂肪酸との部分的エステル化反応、あるいは油脂と、グリセリンとのエステル交換反応等により得ることができる。反応方法は、アルカリ触媒等を用いた化学反応法、リパーゼ等の油脂加水分解酵素を用いた生化学反応法のいずれでもよい。
【0008】
本発明のUCP発現誘導剤は、かかるジアシルグリセロールを有効成分とするものである。本発明のUCP発現誘導剤は、医薬品又は飲食物とすることが好ましい。医薬品としては経口投与剤が好ましい。経口投与剤とする場合には、その形態に特に制限はなく、例えば散剤、顆粒剤、カプセル剤、丸剤、錠剤等の固形製剤、水剤、懸濁剤、乳剤等の液剤等が挙げられる。これらの医薬品は、ジアシルグリセロールの他に、必要に応じて医薬品の形態に応じて一般に用いられる、賦形剤、崩壊剤、結合剤、滑沢剤、界面活性剤、アルコール類、水、水溶性高分子、甘味料、矯味剤、酸味料等を添加し、常法に従って製造することができる。
【0009】
飲食物としては、例えば特定の機能を発揮して健康増進を図る健康食品が挙げられる。具体的には、ジアシルグリセロールを配合した調理油、錠剤、顆粒剤、ドレッシング類、マヨネーズ類、合成クリーム類、チョコレートやポテトチップス等の菓子類等が挙げられる。かかる飲食物は、上記ジアシルグリセロールの他に、飲食物の種類に応じて一般に用いられる食品原料を添加し、常法に従って製造することができる。
【0010】
本発明のUCP発現誘導剤中の、ジアシルグリセロールの配合量は、1〜100%であることが好ましい。医薬品として用いる場合は、30〜90%が好ましい。飲食物として用いる場合は、1〜80%が好ましい。投与量は、UCPを有効に発現させるために、ジアシルグリセロールとして、1〜25g、好ましくは5〜20gを1日1〜数回に分けて投与することが好ましい。
【0011】
UCPには、UCP−1、UCP−2、UCP−3、UCP−4等があるが、本発明のUCP発現誘導剤は、これらのいずれにも有効である。
かかるUCP発現誘導剤を用いれば、ATP合成に共役される化学エネルギーを熱エネルギーに変換できることから、UCP発現誘導剤は、脂質や炭水化物の代謝改善剤として有用である。
【0012】
【実施例】
試験例1
7週齢のWister系雄ラット30匹を1群10匹ずつ3群に分け、第1群にはトリアシルグリセロール20%含有食、第2群には構成アシル基が大豆油脂肪酸由来のジアシルグリセロール20%含有食、第3群には構成アシル基の45%がDHA(ドコサヘキサエン酸)であるジアシルグリセロール20%含有食を、1日1回、午前9時から11時30分の間に給餌した。5日後の給餌後6時間後に、小腸上部及び肝臓を採取し、UCP−2のmRNA及びアクチン蛋白質のmRNAを常法に従って、RT−PCR法により解析した。小腸上部における各群の、アクチン蛋白質のmRNA量に対するUCP−2のmRNA量(mRNA比)の平均値及び標準偏差を表1に示す。
【0013】
【表1】
【0014】
mRNA比は、第3群、第2群、第1群の順に高く、ジアシルグリセロール、特にDHA高含有ジアシルグリセロールのUCP発現誘導効果が認められた。
【0015】
試験例2
ラット由来の小腸上皮細胞株IEC−6を、ウシ胎児血清(FCS)無添加ダルベッコ改変イーグル培地(DMEM培地)で24時間培養後、脂肪酸/ウシ血清アルブミン(BSA)錯体(500mM)を添加し、さらに24時間培養した。添加する脂肪酸は、第1群:脂肪酸無添加、第2群:オレイン酸、第3群:DHA、第4群:EPA(エイコサペンタエン酸)とし、IEC−6におけるUCP2のmRNA発現量を、試験例1と同様にして行った。結果を表2に示す。なお、数値は第1群の発現量を100としたときの相対値で示した。
【0016】
【表2】
【0017】
第2〜第4群では、第1群に比べてIEC−6におけるUCP2mRNAの発現上昇が認められ、その上昇は、第3群、第4群において特に顕著であった。
【0018】
試験例1及び2から、UCP−2の発現レベルは、ジアシルグリセロールの摂取により上昇することが確認された。その程度は、構成脂肪酸が高度不飽和脂肪酸の場合に、より顕著であることが示された。
【0019】
実施例1
表3の組成のソフトカプセル皮(オパール型、重さ150mg)に、ジアシルグリセロール300mgを常法により充填し、ソフトカプセルを製造した。得られたソフトカプセルは、UCP発現誘導作用を示した。
【0020】
【表3】
【0021】
【発明の効果】
本発明のUCP発現誘導剤を用いれば、UCPを有効に発現させることができる。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to an expression inducer for uncoupling protein.
[0002]
[Prior art and problems to be solved by the invention]
Uncoupling refers to inhibiting the energy obtained by electron transfer from coupling to the ATP synthesis reaction in oxidative phosphorylation in vivo, and converts chemical energy conjugated to ATP synthesis to thermal energy. This is one of the important biological functions. Due to the importance of such uncoupling function, many uncoupling agents have been found, and as a substance existing in the living body, for example, uncoupling protein (hereinafter referred to as “UCP”) existing in mitochondria is known. Yes.
[0003]
If the expression of such UCP can be induced, the conversion efficiency of chemical energy conjugated to ATP synthesis to thermal energy is considered to improve. However, until now, almost no UCP expression inducer has been known, It was sought after.
[0004]
[Means for Solving the Problems]
As a result of examining the effect of inducing UCP expression for various lipids and drugs, the present inventor unexpectedly found that diacylglycerol has an excellent effect of inducing UCP expression, and completed the present invention.
[0005]
The present invention provides an uncoupling protein expression inducer containing diacylglycerol as an active ingredient.
[0006]
DETAILED DESCRIPTION OF THE INVENTION
In the present invention, the acyl group constituting diacylglycerol is preferably a saturated or unsaturated acyl group having 8 to 24 carbon atoms, particularly 16 to 22 carbon atoms. There are no particular restrictions on the position or number of unsaturated bonds, but monoene long chain acyl group, ω3 long chain unsaturated acyl group A long-chain unsaturated acyl group in which the first unsaturated bond is located), ω6 long-chain unsaturated acyl group (the position of the unsaturated bond is specified from the ω-position, and the first A long-chain unsaturated acyl group in which a saturated bond is located), and the monoene long-chain acyl group is particularly preferably a hexadecamonoenoyl group, an octadecamonoenoyl group, an eicosadecamonoenoyl group, or a docosadecamonoenoyl group. As the ω3 long-chain unsaturated acyl group, an α-linolenoyl group (allcis-9,12,15-octadecatrienoyl group), an eicosapentaenoyl group, and a docosahexaenoyl group are particularly preferable. Examples of the 6-series long-chain unsaturated acyl group include γ-linolenoyl group (allcis-6,9,12-octadecatrienoyl group), linoleyl group (c, c-9,12-octadecadienoyl group), and arachidoyl. The group (allcis-5,8,11,14-eicosatetraenoyl group) is particularly preferred. The amount of unsaturated acyl groups is preferably 55% by weight (hereinafter simply referred to as “%”) or more of the total acyl groups, more preferably 70% or more, and particularly preferably 90% or more.
[0007]
Such diacylglycerol can be obtained by a partial esterification reaction between glycerin and a saturated or unsaturated fatty acid, or an ester exchange reaction between an oil and fat and glycerin. The reaction method may be either a chemical reaction method using an alkali catalyst or the like, or a biochemical reaction method using an oil and fat hydrolase such as lipase.
[0008]
The UCP expression inducer of the present invention comprises such diacylglycerol as an active ingredient. The UCP expression inducer of the present invention is preferably a pharmaceutical or a food or drink. Oral administration is preferred as the pharmaceutical. In the case of an oral administration agent, the form is not particularly limited, and examples thereof include solid preparations such as powders, granules, capsules, pills and tablets, liquids such as liquids, suspensions and emulsions. . In addition to diacylglycerol, these pharmaceuticals are generally used according to the form of the pharmaceutical as necessary. Excipients, disintegrants, binders, lubricants, surfactants, alcohols, water, water-soluble Polymers, sweeteners, flavoring agents, acidulants and the like can be added and produced according to conventional methods.
[0009]
Examples of foods and drinks include health foods that provide specific functions to promote health. Specific examples include cooking oils, tablets, granules, dressings, mayonnaises, synthetic creams, and confectionery products such as chocolate and potato chips. Such food and drink can be produced according to a conventional method by adding food materials generally used according to the type of food and drink in addition to the diacylglycerol.
[0010]
The blending amount of diacylglycerol in the UCP expression inducer of the present invention is preferably 1 to 100%. When using as a pharmaceutical, 30 to 90% is preferable. When using as food and drink, 1 to 80% is preferable. In order to effectively express UCP, it is preferable to administer 1 to 25 g, preferably 5 to 20 g, as diacylglycerol divided into 1 to several times a day.
[0011]
UCP includes UCP-1, UCP-2, UCP-3, UCP-4, etc. The UCP expression inducer of the present invention is effective for any of these.
If such a UCP expression inducer is used, chemical energy coupled to ATP synthesis can be converted into thermal energy, and thus the UCP expression inducer is useful as an agent for improving lipid or carbohydrate metabolism.
[0012]
【Example】
Test example 1
30 Wister male rats aged 7 weeks were divided into 3 groups of 10 rats per group, the first group containing 20% triacylglycerol, and the second group containing diacylglycerol derived from soybean oil fatty acid. A diet containing 20%, and the third group was fed a diet containing 20% diacylglycerol whose DHA (docosahexaenoic acid) is 45% of the constituent acyl groups once a day between 9 am and 11:30 am . Six hours after feeding 5 days later, the upper small intestine and liver were collected, and UCP-2 mRNA and actin protein mRNA were analyzed by RT-PCR according to a conventional method. Table 1 shows the average value and standard deviation of UCP-2 mRNA amount (mRNA ratio) relative to the amount of actin protein mRNA in each group in the upper small intestine.
[0013]
[Table 1]
[0014]
The mRNA ratio was higher in the order of the third group, the second group, and the first group, and an effect of inducing UCP expression of diacylglycerol, particularly DHA-rich diacylglycerol was observed.
[0015]
Test example 2
Rat-derived small intestinal epithelial cell line IEC-6 was cultured in Dulbecco's modified Eagle medium (DMEM medium) without fetal bovine serum (FCS) for 24 hours, and then a fatty acid / bovine serum albumin (BSA) complex (500 mM) was added. The culture was further continued for 24 hours. Fatty acids to be added are group 1: no fatty acid added, group 2: oleic acid, group 3: DHA, group 4: EPA (eicosapentaenoic acid), and UCP2 mRNA expression level in IEC-6 was tested. Performed as in Example 1. The results are shown in Table 2. In addition, the numerical value was shown by the relative value when the expression level of the first group is 100.
[0016]
[Table 2]
[0017]
In the second to fourth groups, an increase in the expression of UCP2 mRNA in IEC-6 was observed compared to the first group, and the increase was particularly remarkable in the third and fourth groups.
[0018]
From Test Examples 1 and 2, it was confirmed that the expression level of UCP-2 was increased by ingestion of diacylglycerol. The degree has been shown to be more pronounced when the constituent fatty acid is a highly unsaturated fatty acid.
[0019]
Example 1
Soft capsule skins (opal type, weight 150 mg) having the composition shown in Table 3 were filled with 300 mg of diacylglycerol by a conventional method to produce soft capsules. The obtained soft capsule exhibited UCP expression inducing action.
[0020]
[Table 3]
[0021]
【The invention's effect】
If the UCP expression inducer of the present invention is used, UCP can be effectively expressed.
Claims (1)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP23997199A JP4448211B2 (en) | 1999-08-26 | 1999-08-26 | Uncoupling protein expression inducer |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP23997199A JP4448211B2 (en) | 1999-08-26 | 1999-08-26 | Uncoupling protein expression inducer |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2001064171A JP2001064171A (en) | 2001-03-13 |
JP4448211B2 true JP4448211B2 (en) | 2010-04-07 |
Family
ID=17052568
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP23997199A Expired - Fee Related JP4448211B2 (en) | 1999-08-26 | 1999-08-26 | Uncoupling protein expression inducer |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP4448211B2 (en) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6956058B2 (en) | 2001-04-26 | 2005-10-18 | Kao Corporation | Method for improving insulin resistance |
AU2003211635A1 (en) * | 2002-03-04 | 2003-09-16 | The Nisshin Oillio Group, Ltd | Uncoupling protein expression promoter |
AU2003211636A1 (en) * | 2002-03-04 | 2003-09-16 | The Nisshin Oillio Group, Ltd | Body temperature elevating agents |
-
1999
- 1999-08-26 JP JP23997199A patent/JP4448211B2/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
JP2001064171A (en) | 2001-03-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US9962455B2 (en) | Glycerophospholipids for the improvement of cognitive functions | |
JP2704922B2 (en) | Fatty acid composition | |
US6248909B1 (en) | Triglyceride and composition comprising the same | |
JP4391673B2 (en) | Oil composition | |
US5059622A (en) | Method for reducing blood pressure levels in hypertensive persons | |
US20090182050A1 (en) | Salts of Fatty Acids and Methods of Making and Using thereof | |
CA2355341A1 (en) | The use of ara as a supplement for a lactating woman | |
CN101321477A (en) | Salts of fatty acids and methods of making and using thereof | |
JP4448211B2 (en) | Uncoupling protein expression inducer | |
JP2006306813A (en) | Mast cell increase inhibitor | |
US20120184760A1 (en) | Removal of monoglycerides from fatty acid concentrates | |
JP2002302441A (en) | Composition and food and drink for obtunding symptom of premenstrual syndrome | |
JP2001354556A (en) | Prophylactic or therapeutic agent for hypertension | |
JP5759663B2 (en) | Skin barrier function improver, etc. | |
JP3947322B2 (en) | Pharmaceutical composition and health food containing polyunsaturated fatty acid | |
CN106232113B (en) | Absorption enhancer for unsaturated fatty acid | |
JPH11116473A (en) | Medicinal composition containing polyvalent unsaturated fatty acid and health food | |
WO2004087119A2 (en) | Compositions containing superoxide dismutase and a selected et 5-lipoxygenase inhibitor and uses thereof | |
JPH0753410A (en) | Method for reducing bitter taste and composition reduced in bitter taste | |
CN107249581A (en) | Phospholipid preparations for improving communication skill |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20050801 |
|
RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20050801 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090203 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20090609 |
|
A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090909 |
|
A911 | Transfer of reconsideration by examiner before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20091110 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20100119 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20100122 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130129 Year of fee payment: 3 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130129 Year of fee payment: 3 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20140129 Year of fee payment: 4 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
LAPS | Cancellation because of no payment of annual fees |