WO2007049818A1 - Anti-fatty liver, anti-obesity or hypolipidemic composition - Google Patents

Abstract

Disclosed are: an anti-fatty liver or anti-steatohepatitis composition comprising lysine in an amount of not less than 5.0% and less than 65.0%, threonine in an amount of not less than 5.0% and less than 65.0%, leucine in an amount of not less than 1.0% and less than 35.0%, isoleucine in an amount of not less than 1.0% and less than 35.0% and valine in an amount of not less than 1.0% and less than 35.0% by mole relative to the total amount of the amino acids contained in the composition; and an anti-obesity or hypolipidemic composition which comprises lysine, threonine, leucine, isoleucine and valine in the same amounts as those mentioned above and does not contain at least one non-essential amino acid selected from the group consisting of proline, glycine, tyrosine and arginine.

Description

 Specification

 Anti-fatty liver, anti-obesity and anti-hyperlipidemia composition Technical Field

 The present invention relates to lysine, threonine, leucine, isoleucine and parin for the purpose of suppressing and improving the development of fatty liver (especially caused by ingestion of high fat diet, etc.), 'steatohepatitis, obesity and hyperlipidemia. The present invention relates to a composition for suppressing the onset of and improvement of fatty liver, steatohepatitis, obesity and hyperlipidemia. Background art

 At present, obesity and diabetes are rapidly increasing in Japan, but the underlying factors are increased obesity due to high fat diet and lack of exercise, and associated increase in insulin resistance. It is generally known that increased daily fat intake leads to obesity and various metabolic disorders associated therewith. Increased fat intake is the most important factor causing insulin resistance, and its mechanism is being elucidated at the molecular level. The pathophysiology that occurs on the basis of this insulin resistance includes so-called metabolic syndrome and diabetes, hyperlipidemia, hypertension, arteriosclerosis, fatty liver, hyperuricemia, and so on. Yes.

Among these pathologies, hyperlipidemia and fatty liver are extremely important risk factors. In particular, it has been known that fatty liver usually develops when alcohol is consumed on a daily basis. However, in recent years, the proportion of fatty liver caused by obesity due to ingestion of high-fat diet and lack of exercise has also risen rapidly, and this is not limited to alcohol consumption, but fatty liver results from lifestyle imbalances including dietary habits. Suggests that. It is known that fat is accumulated not only in the liver but also in the whole body when eating a diet that causes fatty liver. Accumulation of visceral fat is caused by arteriosclerotic diseases, hyperlipidemia, hypertension May increase the risk of diabetes. That is, fatty liver is a lifestyle-related disease It is one of the most important risk factors, and solutions that include dietary ingredients are required.

 Recently, many lifestyle-related diseases caused by westernization of eating habits and changes in lifestyle habits have become a problem. The causes of lifestyle-related diseases are obesity and hyperlipidemia, as well as the accumulation of visceral fat, especially fat As mentioned above, the liver is important. Fatty liver is a condition in which excess neutral fat in the liver cells of the liver has accumulated. The liver biosynthesizes fat for use as an energy source, some of which is stored in hepatocytes. However, when the amount of fat biosynthesized is relatively large compared to the fat consumed as energy in the hepatocytes, the fat accumulates in the hepatocytes, and when such a state progresses, it becomes fatty liver. Fatty liver is a pathological condition caused by lifestyle such as eating and drinking, and is one of the factors that cause serious lifestyle-related diseases. The treatment is: In the case of fatty liver associated with increased fat intake, Diet therapy and exercise therapy are the main methods, and in the case of alcoholic fatty liver, the amount of alcohol consumption is mainly reduced. As described above, in order to treat or prevent fatty liver, improvement of daily eating habits occupies a great weight, and a diet component having anti-fatty liver action is required.

Under such circumstances, intake of polyunsaturated fatty acids (hereinafter referred to as PUFA) such as eicosapentaenoic acid (hereinafter referred to as EPA) and docosahexaenoic acid (hereinafter referred to as DHA), which are abundant in fish oil, liver oil, etc. It has become clear that it has been shown to improve fats and suppress fat accumulation in the liver. The mechanism of action is also becoming clear at the molecular level. Specifically, PUFA is a series of fatty acid biosynthetic enzymes such as ATP citrate lyase (hereinafter ACL), fatty acid syntha se (hereinafter FAS), stearoyl CoA desaturase 1 (hereinafter S CD 1), etc. Increases the gene expression level of sterol regulatory element binding protein 1 c (hereinafter referred to as SREBP lc) Decreases the gene expression level, and increases the gene expression of the three oxidase groups responsible for fatty acid degradation peroxisome It is known to increase the gene expression level of proliferators-activated receptor-H (PPAR a). In addition, prevention and improvement of fatty liver or hyperlipidemia by PUFA This is described in Japanese Patent Application Laid-Open No. Hei 8-023881 or Japanese Patent Application Laid-Open No. 91-194362.

 It has also been reported that plant fibers obtained from various cereals are effective in suppressing fatty liver. JP-A-1-242530 describes that an extract obtained by removing starchy protein or the like from corn bran or wheat bran suppresses alcoholic fatty liver.

 Other than that, an alcoholic fatty liver inhibitory composition containing at least one of amino acids such as arginine and the like and a thiamine compound that has a glucagon secretion activity has been reported (JP-A-10-158). 1 See No. 70).

 As described above, there are reports on the inhibitory components of alcoholic fatty liver, and dietary components that reduce liver fat by ingesting a high-fat diet and further suppress fatty liver are sufficient except for PUFA. It is not clear.

 There have been few reports on compositions consisting of amino acids or amino acids having anti-obesity, anti-hyperlipidemia, anti-fatty liver and anti-fatty hepatitis effects. Japanese Patent Application Laid-Open No. 6-24977 is an example, including nine essential amino acids consisting of threonine, proline, valine, isoleucine, leucine, tyrosine, phenylalanine, lysine, methionine, tryptophan, histidine, and arginine and 3 A composition comprising two types of non-essential amino acids (total of 12 types) as an active ingredient has anti-obesity and anti-hyperlipidemic effects on obesity and hyperlipidemia caused by a high sucrose or high fructose diet. Show. However, this document does not actually show an effect on obesity or hyperlipidemia caused by a high fat diet, which is a problem in chicken. In addition, there is no description or disclosure of anti-fatty liver action.

On the other hand, it has been reported that visceral fat increases and especially fatty liver is induced when protein nutrition disorders such as intake of a low protein diet (JP n JP harma co 1. Mar; 1 9 (1) : 74-88 (1 969)). In addition, it has been reported that experimental animals such as rats fed diets deficient or low in essential amino acids such as lysine and threonine have fatty liver (JL ipid Res. J ul; 7 (4): 473-8 (1 966)). However, the effects of ingestion of these proteins and amino acids on visceral fat accumulation and fatty liver have been clarified in the absence of sufficient protein that can be ingested with normal diet. In addition, regarding the onset of obesity, hyperlipidemia and fatty liver associated with the increase in fat intake due to intake of high fat diet, etc., the effects of ingestion of these proteins and amino acids have not been clarified as described above. . Disclosure of the invention

 An object of the present invention is to provide a composition that significantly suppresses and ameliorates fatty liver (especially caused by intake of a high fat diet), steatohepatitis, manure, and hyperlipidemia. '

 As a result of intensive studies to achieve the above-mentioned object, the present inventors have found that a composition containing lysine, threonine, leucine, isoleucine and parin has an excellent anti-fatty liver 'anti-fatty hepatitis action, A composition containing lysine, threonine, leucine, isoorcin, and valine, and not containing at least one non-essential amino acid selected from the group consisting of proline, glycine, tyrosine, and arginine And the present invention was completed.

 Therefore, the present invention is as follows.

 (1) Lysine, threonine, leucine, isoleucine, and valine are each included in a molar ratio of lysine 5.0% to 65.

Less than 0%, Threonine 5.0% or more ~ 65.0% or less, Leucine 1.0% or more ~

Less than 35.0%, isoleucine 1. 0% to less than 35.0% and parin 1.

A composition for anti-fatty liver or anti-fatty hepatitis, comprising 0% or more and less than 35.0%.

(2) The composition according to (1), wherein the fatty liver is fatty liver induced by intake of a high fat diet. (3) Lysine, threonine, ώisin, isoleucine, and parin as molar constituent ratios with respect to all amino acids in the composition, lysine 5.0% to less than 65.0%, threonine 5.0% to 65% Less than 0%, leucine 1. 0% to less than 35.0%, isoleucine 1. 0% to less than 35.0% and parin 1. 0% to less than 35.0%, and An anti-obesity composition comprising no at least one non-essential amino acid selected from the group consisting of proline, glycine, tyrosine and arginine.

 (4) Lysine, threonine, leucine, isoleucine and valine as molar constituent ratios with respect to all amino acids in the composition, respectively, lysine 5.0% to less than 65.0%, threonine 5.0% to 65%. Less than 0%, leucine 1., 0% or more

Less than 35.0%, Isoleucine 1. 0% to less than 35.0% and Palin 1 ,.

A composition for anti-obesity, characterized by being contained in a range of 0% or more and less than 35.0% and not containing at least one non-essential amino acid selected from the group consisting of proline, glycine and arginine .

 (5) Lysine, threonine, leucine, isoleucine and valine are each included in a molar ratio of lysine of 5.0% to 65.

Less than 0%, Threonine 5.0% or more ~ 65.0% or less, Leucine 1.0% or more ~

35. below 0%, isoleucine _1.0>% or more to 35. Less than 0% and Palin 1.

Anti-high fat, characterized by containing in the range of 0% to less than 35.0% and not containing at least one non-essential amino acid selected from the group consisting of proline, glycine, tyrosine and arginine A composition for blood pressure.

 (6) Lysine, threonine, leucine, isoleucine, and valine are each included in a molar ratio of lysine 5.0% to 65.

Less than 0%, Threonine 5.0% or more to less than 65.0%, Leucine 1.0% or more to less than 35.0%, Isoleucine 1.0% or more to less than 35.0% or Palin 1.

0% to less than 35.0%, and proline, glycine and arginium An antihyperlipidemic composition characterized by not containing at least one non-essential amino acid selected from the group consisting of nin. '

 (7) Add lysine, threonine, leucine, isoleucine and parin so that the essential amino acid non-essential amino acid ratio in the composition (hereinafter referred to as EAA / NEAA ratio) is 0.50-3.50 in molar ratio. The composition according to any one of (1) to (6), which is contained.

 (8) Lysine, threonine, leucine, isoleucine, and valine are each included in a molar ratio of lysine 5.0% to 65.

0% unprecedented, threonine 5.0% or more to less than 65.0%, leucine 1.0% or more to less than 35.0%, isoleucine 1.0. / ^/ ₀ or more to 35. Less than 0% and Palin 1.

A drug for anti-fatty liver or anti-fatty hepatitis containing in the range of 0% or more to less than 35.0%.

(9) Lysine ', threonine, leucine, isoleucine and valine as molar constituent ratios with respect to all amino acids in food and drink, lysine 5.0% to less than 65.0%, threonine 5.0% to 65%. , Less than 0%, Loisin 1.0% or more to 35.0% less, Isoleucine 1. 0% or more to less than 35.0% and Palin 1.

A food or drink for preventing or improving fatty liver or steatohepatitis, which is contained in the range of 0% or more to less than 35.0%.

 (10) The food or drink according to (9), which is labeled as being used for the prevention or improvement of fatty liver or steatohepatitis.

(1 1) Lysine, threonine, leucine, isoleucine and valine as molar constituent ratios with respect to all amino acids in the drug, respectively, lysine 5.0% to less than 65.0%, threonine 5.0% to 65.0% Less than%, leucine 1. 0% to less than 35.0%, isoleucine 1. 0% to less than 35.0%, and parin 1. 0% to less than 35.0%, and proline. An anti-obesity medicament characterized by not containing at least one non-essential amino acid selected from the group consisting of glycine, tyrosine and arginine. (1 2) Lysine, threonine, 'leucine, isoleucine, and valine as molar constituent ratios with respect to all amino acids in the drug, respectively, lysine 5.0% to less than 65.0%, threonine 5.0% to 65%. Less than 0%, leucine 1. 0% to less than 35.0%, isoleucine 1. 0% to less than 35.0% and valine 1. 0% to less than 35.0%, and proline An anti-obesity medicament characterized by not containing at least one non-essential amino acid selected from the group consisting of glycine and arginine.

 (1 3) Lysine, threonine, leucine, isoleucine and valine as molar constituent ratios with respect to all amino acids in food and drink, respectively, lysine 5.0% to less than 65.0%, threonine 5.0% to 65%. Less than 0%, leucine 1. 0% to less than 35.0%, isoleucine 1. 0% to less than 35.0% and parin 1. 0% to less than 35.0%, and proline A product for preventing or ameliorating obesity, characterized by not containing at least one non-essential amino acid selected from the group consisting of glycine, tyrosine and arginine.

 (14) Lysine, threonine, leucine, isoleucine and valine as molar constituent ratios with respect to all amino acids in food and drink, respectively, lysine 5.0% to less than 65.0%, threonine 5.0% to 65.0% Less than%, Leucine 1. 0% or more to less than 35.0%, Isoleucine 1. (^. /. Or more to less than .0-% and Palin from 1.0% or more to 35.0 or less. And at least one non-essential amino acid selected from the group consisting of proline, glycine and arginine.

 (1 5) The food or drink according to (1 3) or (14), which is labeled for use in preventing or improving obesity.

 (16) Lysine, threonine, leucine, isoleucine, and valine are each included in a molar ratio of lysine 5.0% to 65.

Less than 0%, Threonine 5.0% or more to less than 65.0%, Leucine 1.0% or more to less than 35.0%, Isoleucine 1.0% or more to less than 35.0% or Palin 1. Antihyperlipidemic, characterized by containing in the range of 0% to less than 35.0% and not containing at least one non-essential amino acid selected from the group consisting of proline, glycine, tyrosine and arginine Medicinal drugs.

 (1 7) Lysine, threonine, leu, cin, isoleucine and valine as molar constituent ratios with respect to all amino acids in pharmaceuticals, respectively, lysine 5.

Less than 0%, Threonine 5.0% or more to less than 65.0%, Leucine 1.0% or more to less than 35.0%, Isoleucine 1.0% or more to less than 35.0% or Palin 1.0% or more 35. An antihyperlipidemic drug characterized by containing less than 0% and not containing at least one non-essential amino acid selected from the group consisting of proline, glycine and arginine.

(1 8) lysine, threonine, leucine, isoleucine and valine, as the molar component ratio to total amino acids in each in food or drink, lysine 5. 0% or more to 65. Less than 0%, threonine 5.0 ⁰ / shed more ~ 6.5. Less than 0%, Leucine 1. 0% or more to less than 35.0%, Isoleucine 1. 0% or more to less than 35.0% and Parin 1. 0% or more to less than 35.0%, A food or drink for preventing or ameliorating hyperlipidemia, characterized by not containing at least one non-essential amino acid selected from the group consisting of proline, glycine, tyrosine and arginine.

 (1 9) Lysine, threonine, leu, n, isoleucine and valine as molar constituent ratios with respect to all amino acids in food and drink, respectively, lysine 5.0% to less than 65.0%, threonine 5.0% or more ~ 65.0%, leucine 1. 0% to less than 35.0%, isoleucine 1. 0% to 35.0% and valine 1. 0% to 35.0% And a food or drink for the prevention or amelioration of hyperlipidemia, characterized by not containing at least one non-essential amino acid selected from the group consisting of proline, glycine and arginine.

(20) The food or drink according to (1 8) or (19), which is labeled as being used for the prevention or improvement of hyperlipidemia. (2 1) Lysine, threonine, 'leucine, isoleucine and parin as molar constituent ratios to all amino acids, lysine 5.0% to less than 65.0%, threonine 5.0% to 65.0% Less than, leucine 1. 0% to less than 35.0%, isoleucine 1. 0% to less than 35.0% and parin 1. 0% to less than 3 5.0%, lipid biosynthesis Regulatory gene expression inhibitor.

 (22) The inhibitor according to (2 1), wherein the lipid biosynthesis control gene is a SREBP1c gene, a HMG CAS1 gene, an ACL gene, or a FAS gene.

 (23) Lysine, threonine, leucine, isoleucine and valine as molar constituent ratios with respect to all amino acids in the composition, lysine 5.0% to less than 65.0%, threonine 5.0% to 65.0% A composition containing less than%, leucine 1.0% to less than 35.0%, isoleucine 1.0% to less than 35.0%, and parin 1.0% to less than 35.0%.

 (24) Lysine, threonine, leucine, isoleucine and valine as molar constituent ratios with respect to all amino acids in the composition, respectively, lysine 5.0% to 65.0%, threonine 5.0% to 65%. Less than 0%, Leucine 1. 0% or more

Less than 35.0%, isoleucine 1, 0% to less than 35.0% and valine 1.

A composition comprising 0% or more and less than 35.0% and not containing at least one non-essential amino acid selected from the group consisting of proline, glycine, tyrosine and arginine.

 (25) characterized in that lysine, threonine, leucine, isoleucine and valine are contained so that the EAA / NE ratio in the composition is 0.50 to 3.50 in molar ratio. ) Or (24).

 (26) Lysine, threonine, leucine, isoleucine and valine as molar constituent ratios with respect to all amino acids in the composition, respectively, lysine 5.0% to less than 65.0%, threonine 5.0% to 65.0% Less than%, leucine 1. 0% or more

Less than 35.0%, isoleucine 1. 0% to less than 35.0% and parin 1. A method for preventing or treating fatty liver or steatohepatitis, comprising administering a composition containing 0% or more to less than 35.0% to the administration subject.

 (27) Lysine, threonine, leucine, isoleucine and valine as molar constituent ratios with respect to all amino acids in the composition, lysine 5.0% to less than 65.0%, threonine 5.0% to 65.0% Less than%, leucine 1. 0% or more

Less than 35.0%, isoleucine 1. 0% to less than 35.0% and parin 1.

A composition containing 0% or more and less than 35.0% and not containing at least one non-essential amino acid selected from the group consisting of proline, glycine, tyrosine and arginine is administered to the administration subject A method for preventing or treating obesity. (28) Lysine, threonine, leucine, isoleucine, and valine are each included in a molar ratio of lysine 5.0% to 65.

Less than 0%, threonine 5.0% or more to less than 65.0%, leucine 1.0% or more to

Less than 35.0%, isoleucine 1. 0% to less than 35.0% and parin 1.

A composition containing 0% or more and less than 35.0% and containing at least one non-essential amino acid selected from the group consisting of proline, glycine, tyrosine and arginine is administered to a subject. A method for preventing or treating hyperlipidemia.

 (29) Lysine, threonine, leucine, isoleucine, and valine are each included in molar ratios of lysine to all amino acids of lysine 5.0% to less than 65.0%, threonine 5.0% to 65.0% %, Leucine 1. 0% to less than 35.0%, isoleucine 1. 0% to less than 35.0% and parin 1. 0% to less than 35.0%. A method for suppressing lipid biosynthesis control gene expression, comprising administering to a subject.

(30) As a molar composition ratio with respect to all amino acids in the composition, lysine 5.0% to less than 65.0%, threonine 5.0% to less than 65.0%, oral isine 1.0% or more Anti-fat liver or anti-fat containing in a range of less than 35.0%, isoleucine 1.0% or more to less than 35.0% and palin 1.0% or more to less than 35.0% Use of lysine, threonine, leucine, iso-oral isine and valine for the manufacture of a composition for steatohepatitis.

 (3 1) The molar composition ratio of all amino acids in the composition is lysine 5.0% to less than 65.0%, threonine 5.0% to less than 65.0%, oral isine 1.0% More than 3 to less than 35.0%, isoleucine 1.0% or more to less than 35.0% and parin 1. More than 0% to less than 35.0%, and it consists of proline, glycine, tyrosine and arginine Use of lysine, threonine, leucine, isoleucine and parin for the manufacture of an anti-obesity composition which does not contain at least one non-essential amino acid selected from the group.

 (32) The molar composition ratio of all amino acids in the composition is lysine 5.0% to less than 65.0%, threonine 5.0% to less than 65.0%, oral isine 1.0% or more ~ 35.0%, isoleucine 1. 0% to less than 35.0% and parin 1. 0% or more to less than 35.0%, and a group consisting of proline, dalysin, tyrosine and arginine Use of lysine, threonine, leucine, isoleucine and parin to produce an antihyperlipidemic composition which does not contain at least one non-essential amino acid selected from the above.

 (33) The molar composition ratio of all amino acids in the preparation is lysine 5.0% to less than 65.0%, threonine 5.0% to less than 65.0%, oral isine 1.0% or more 30.0% or less, isoleucine 1.0% or more to less than 35.0% and parin 1. 0% or more to less than 35.0% Use of lysine, threonine, leucine, isoleucine and parin.

The composition containing lysine, threonine, leucine, isoleucine and parin provided by the present invention suppresses fatty liver and steatohepatitis. The composition for anti-fatty liver and steatohepatitis of the present invention is particularly effective in steatohepatitis and steatohepatitis caused by ingestion of a high fat diet. The lysine, threonine, leucine, isoleucine and valine provided by the present invention, and proline, darin The composition characterized by not containing at least one non-essential amino acid selected from the group consisting of syn, tyrosine and argini is useful for anti-obesity and anti-hyperlipidemia.

 Furthermore, since the composition of the present invention comprises an amino acid as an active ingredient, it is highly safe and has few side effects. Therefore, the composition of the present invention can be administered for a long period of time. In fatty liver, steatohepatitis, obesity and hyperlipidemia It can be used advantageously for prevention, treatment and improvement. The lipid biosynthesis regulating gene expression inhibitor of the present invention can be used as an experimental reagent in the fields of physiology and biochemistry in addition to its use as a medicament as described above. Brief Description of Drawings

 FIG. 1 shows mRNA expression level of SREB P 1 c gene in liver (A) and AMPK phosphorylation in skeletal muscle (B). (A): The relative amount of mRNA is expressed by standardizing with the amount of 18 S liposomal RNA. Data represent mean soil standard deviation. There is a significant difference in mean values between experimental groups that do not have the same alphabet. P 0.05 (Tukey HSD) (B): Dumps were extracted from soleus muscle and Western blotting was performed using anti-AMPK and anti-AMPK phosphorylated antibodies. The graph is expressed as a relative value with the STD group as 1. Data represent mean soil standard deviation. There is a significant difference in mean values between experimental groups that do not have the same alphabet.

p <0.05 (Tukey HSD)

Fig. 2 shows typical liver tissue slices in the HFD group and the 8% EAA ^/ HFD group.

Fig. 3 shows the liver (A), liver lipid content (B), and blood GOT and GPT values (C) of obZob mice. Data represent mean soil standard deviation. There is a significant difference in mean values between experimental groups that do not have the same alphabet. P <0.05 (Tukey HSD) Figure 4 shows the weight gain of (A) HFD group, EAA / HFD group, EAA + PrοFD group and EAA + G1y / HFD group. Data represent mean soil standard deviation. (B) STD group, HFD group, E AA / HFD group and E AA + Arg / HFD group Represents fat weight. Data represent mean soil standard deviation. In the figure, * indicates that there is a significant difference in the STD group. (C) Represents blood cholesterol levels in the HFD group, EAAZHFD group, EAA + A rg ZHFD group, and EAA + G 1 y / HFD group. Data represent mean soil standard deviation. In the figure, * indicates that there is a significant difference from the HFD group.

 Figure 5 shows the weight gain of (A) HFD group, EAA / HFD group, EAA-B ^ HFD group, EAA-K / HFD group, and EAA-T / HFD group. Data represent mean soil standard deviation. (B) Shows the total fat weight of HFD, EAA / HFD, EAA-K / HFD, and EAA_TZHFD groups. Data represent mean soil standard deviation.

 (C) The blood lepton concentration in the HFD group, EAAZHFD group, EAA—B ^ HFD group, EAA—K / HF D group, and EAA—T / HFD group. The data represents the average person standard deviation. (D) Liver weight of HFD group, EAAZHFD group, EAA-B / HFD group, EAA-K / HFD group, and EAA-T / HFD group. Data represent average soil standard deviation. (E) Liver triglycerides in HFD, EAAZHFD, EAA-B / HFD, EAA-KZHFD, and EAA-T / HFD groups. Data represent mean soil standard deviation. (F) Shows liver cholesterol in the HFD, EAA-HFD, EAA-B / HFD, EAA-K / HFD, and EAAA-T / HF groups. Data represent mean soil standard deviation. (A) to (F) In the figure, * indicates that there is a significant difference from the HFD group.

Figure 6 shows the weight gain of (A) HFD group, EAAZHFD group, EAA-K 60 HFD group, and EAA-T 6 OZHFD group. Data represent mean soil standard deviation. (B) Blood levtin concentrations in HFD, EAAZHFD, EAA-K 60 HFD, and EA A-T60 / HFD groups are shown. Data represent mean soil standard deviation. (C) The blood cholesterol levels of the HFD group, EAA / HFD group, EAA—K 60 HFD group, and EA A—T 60 HFD group are shown. Data represent mean soil standard deviation. (D) HFD group, EAA / HFD group, EAA—K 60 / HFD group, and And liver weight of EAA-T 6 OZHFD group. Data represent mean soil standard deviation. In (A) to (D), * indicates a significant difference from the HFD group.

 Figure 7 shows the liver weights of (A) HFD group, EAAZHFD group, EAA-B / HFD group, EAA-KZHFD group, and EAA-T / HFD group. Data represent mean soil standard deviation. (B) Triglycerides in the liver of HFD, EAA / HFD, EAA—BZHFD, EAA—KZHFD, and EAA—T / HFD groups. Data represent mean ± standard deviation. (C) HFD group, EAAZHFD group, EA 8_8 no? Shows liver cholesterol in the ^ 1 ^ 0 group and the EAA-T / HFD group. Data represent mean soil standard deviation. In the figures (A) to (C), * indicates a significant difference from the HFD group. ;

 FIG. 8 shows liver weights of (A) HFD group, EAA-K 6 OZHFD group, and EAA-T60 HFD group. Data represent mean soil standard deviation. (B) Liver triglycerides in the HFD, EAA-K 6 OZHFD, and EAA-T 6 O ^ HFD groups. Data represent mean soil standard deviation. (A) In the figures in (B), * indicates that there is a significant difference from the HFD group. BEST MODE FOR CARRYING OUT THE INVENTION

<Essential amino acids>,

 Essential amino acids (hereinafter referred to as EAA) used in the present invention are lysine, threonine, leucine, isoleucine and parin. Regarding the isomers of these amino acids, any of L_ form, D-form, and DL_ form can be used, but L-form is preferably used.

In this specification, an amino acid includes a salt thereof. In other words, the amino acids used as the active ingredient in the present invention can be used not only in the form of educts but also in the form of salts for some or all of them. Examples of the salt form include acid addition salts and salts with a salt group, and it is preferable to select a salt of the amino acid that is acceptable as a pharmaceutical or a food or drink. Forms a salt acceptable as a medicine or food and drink Examples of the acid to be used include inorganic acids such as hydrogen chloride, hydrogen bromide, sulfuric acid and phosphoric acid, and organic acids such as acetic acid, lactic acid, citrate, tartaric acid, maleic acid, fumaric acid and monomethylsulfuric acid.

<Composition>

 The composition of the present invention comprises lysine, threonine, leucine, isoleucine, and parin as molar constituent ratios with respect to all amino acids in the composition, respectively, lysine 5.0% to less than 65.0%, threonine 5.0% or more ~ 65.0%, oral isine 1.0% or more to less than 35.0%, isoleucine 1. 0% or more to less than 35.0% and parin 1. 0% or more to less than 35.0% Composition or lysine 5.0% or more to less than 65.0%, Threonine 5.0% or more to 65., less than 0%, Leucine 1.0% or more to less than 35.0%, Isoleucine 1. A composition containing 0% or more and less than 35.0% and valine in the range of 0% or more and less than 35.0% and not containing at least one non-essential amino acid selected from proline, glycine, tyrosine and arginine It is. Further, a composition containing the essential amino acid Z non-essential amino acid ratio (hereinafter referred to as EAAZNEAA ratio) in the composition to a molar ratio of 0.50 to 3.50 is also a composition of the present invention.

 The anti-fatty liver or anti-fatty hepatitis composition of the present invention comprises lysine, threonine, leucine, isoleucine and norin as active ingredients, and a composition for suppressing and improving fatty liver or steatohepatitis It is a thing. The anti-fatty liver or anti-fatty hepatitis composition of the present invention is effective against any fatty liver and steatohepatitis, but is particularly effective against fatty liver and steatohepatitis caused by intake of a high-fat diet.

The anti-obesity composition and anti-hyperlipidemic composition of the present invention contain lysine, threonine, leucine, isoleucine and valine as active ingredients, and at least one selected from proline, glycine, tyrosine and arginine. One non-essential amino acid is not contained. Among these non-essential amino acids, it is preferable not to contain at least one non-essential amino acid selected from proline, dalysin and arginine. The anti-obesity composition of the present invention is effective in suppressing the decrease or increase in body weight and body fat of obese people. The antihyperlipidemic composition of the present invention is effective against hyperlipidemia associated with abnormal lipid metabolism such as obesity, fatty liver and diabetes.

 In the composition for anti-fatty liver, the composition for anti-fatty hepatitis, the composition for anti-obesity and the composition for anti-hyperlipidemia of the present invention, the molar composition ratio of five amino acids to all amino acids. Lysine 5.0 or more to less than 65.0, threonine 5.0 or more to less than 65, leucine 1.0 or more to less than 35.0, isoleucine 1.0 or more to less than 35.0, noble phosphorus 1.0 or more The range is less than 35.0. Preferably, lysine 15.0 or more to less than 45.0, Threonine 10.0 or more to less than 45.0, Mouth Icine 15.0 or more to less than 35.0, Isoleucine 10.0 or more to 20.0 Less than, valine 10.0 or more and less than 20.00.

 The composition for anti-fatty liver, the composition for anti-fatty hepatitis, the composition for anti-obesity and the composition for anti-hyperlipidemia of the present invention is used as a pharmaceutical composition and a food composition. Examples of the subject of administration (intake) include mammals (eg, humans, mice, rats, hamsters, rabbits, cats, dogs, sushi, hidges, monkeys, etc.).

 Here, with respect to the anti-fatty liver composition, anti-fatty hepatitis composition, anti-obesity composition, and anti-hyperlipidemia composition of the present invention, the dosage form when used as a pharmaceutical is not particularly limited. However, it can pass through general administration routes such as oral administration, rectal administration, injection, and administration by infusion. Oral dosage forms include granules, fine granules, powders, coated tablets, tablets, suppositories, powders, (micro) capsules, chewables, syrups, juices, solutions, suspensions, emulsions In addition, general dosage forms of pharmaceutical preparations such as those for direct intravenous injection, infusions for infusion administration, and other preparations that prolong the release of active substances can be adopted as injections.

The dosage in the case of using the composition of the present invention as a pharmaceutical (pharmaceutical composition) varies depending on the age, weight or pathological state, dosage form, or administration method of the subject patient. For the purpose of adults (as 6 O kg body weight) per day as an active ingredient of the composition for anti-fatty liver or anti-fatty hepatitis of the present invention The dosage of the acid is usually 100 m to 50 g, preferably 500 mg to 15 g.

 For the purpose of anti-obesity, the dosage of amino acid as an active ingredient of the anti-obesity composition is usually 100 mg to 50 g, preferably 50 Omg to 15 g.

 For anti-hyperalumemia, the dose of amino acid as the active ingredient of the anti-hyperlipidemic composition is usually 1 O Omg to 50 g, preferably 500 mg to: 15 g . The daily dose can be administered once or divided into several (eg, three) doses. It does not matter before, during, after, or between meals. Preferably after meal, for example, 0 hours to 2 hours after meal, preferably 0 hours to 1 hour after meal, more preferably 0 hours to 0.5 hour after meal. The administration period is not particularly limited. ,

 These medicaments can be formulated by conventional methods. Various pharmacologically acceptable pharmaceutical substances (as adjuvants etc.) can be added as required by the pharmaceutical preparation. The drug substance can be appropriately selected depending on the dosage form of the drug product. For example, the excipient, diluent, additive, disintegrant, binder, coating agent, lubricant, lubricant, lubricant, flavor Agents, sweeteners, solubilizers and the like. Furthermore, specific examples of pharmaceutical substances include magnesium carbonate, titanium dioxide, ratatoose, mannitol and other sugars, talc, milk protein, gelatin, starch, cellulose and its derivatives, animal and vegetable oils, polyethylene glycol, , Solvents (eg, sterilized water, monohydric or polyhydric alcohols such as glycerol), and the like.

 In addition, the composition for anti-fatty liver, the composition for anti-fatty hepatitis, the composition for anti-obesity and the composition for anti-hyperlipidemia of the present invention comprises an anti-fatty liver agent, an anti-fatty hepatitis agent, an anti-obesity agent and an anti-high Used as a lipemia agent.

Since the active ingredient is an amino acid, the composition of the present invention is excellent in safety and can be easily used in the form of food and drink. When the composition of the present invention is used as a food or drink (food composition), any form may be used as long as it is in the form of a general food or drink containing a high content of these active ingredients. For example, an appropriate flavor can be added to make a drink (eg, soft drink, powdered drink). Specifically, juice, cow Can be mixed with milk, confectionery, jelly, etc. It is also possible to provide such foods and drinks as functional foods in addition to general foods including so-called health foods. These functional foods include anti-fatty liver, anti-fatty hepatitis, anti-obesity and / or anti-high foods. Included are foods and drinks that are labeled as being used for lipidemia, especially foods for specified health use or functional nutritional foods.

 Furthermore, the composition of the present invention can be used as a concentrated liquid food or a food supplement. When used as a food supplement, it can be prepared in the form of tablets, capsules, powders, granules, suspensions, chewables, syrups and the like. The food supplement in the present invention refers to those taken for the purpose of supplementing nutrition in addition to those taken as food, and includes nutritional supplements and supplements.

 Since the composition of the present invention contains an amino acid as an active ingredient, it has extremely low toxicity, and its dosage can be set in a very wide range.

 For example, the intake of amino acids in the food or drink for preventing or ameliorating fatty liver or steatohepatitis according to the present invention under the condition that the protein energy ratio of the daily meal is 10% or more is usually 0.5%. ~ I 0 g, daily intake is lg ~ 50 g, preferably, intake is 1-5 g at a time, and daily intake is 3-15 g.

 The intake of amino acids in the food or drink for preventing or ameliorating obesity according to the present invention under the same conditions is usually 0.5 to 10 g, and the daily intake is lg to 50 g. The intake is 1-5 g at a time, and the daily intake is 3-15 g. Similarly, the intake of amino acids in the food or drink for preventing or ameliorating hyperlipidemia of the present invention under the same conditions is usually 0.5 to 10 g at a time, and the daily intake is lg ˜50 g, preferably, intake is 1 to 5 g at a time, and Θ is 3 to 15 g.

The above intake can be packaged in one unit. For example, when the food is a so-called health food, the above amount may be packaged in the form of the intake unit amount per meal, and when the food is a health drink, Above quantity This is a form in which Dori Siku, suspended or dissolved, is put in a bottle bowl in the form of a drink per serving.

The essential amino acid / non-essential amino acid ratio (hereinafter referred to as EAAZNEAA ratio (molar ratio)) in plant or animal protein that can be ingested as a diet is 0.46 for cereals, vegetables, seafood, meat and milk, respectively. The total amount of essential amino acids represented by lysine, threonine, leucine, isoleucine and parin is small compared to the total amount of non-essential amino acids, and is constant at 0.50, 0.69, 0.68 and 0.75. No (Japanese food standard ingredient table). Therefore, in order to efficiently consume these essential amino acids, the protein intake must be increased, but the protein content in plant-derived foods is low, and animal-derived meat has the same level of animal fat. It will not be an essential solution. On the other hand, an increase in the total intake of Tajipa can also put a burden on the kidneys and liver. Therefore, there is a need for a composition that can efficiently take only the necessary essential amino acids. For example, an essential amino acid comprising lysine, threonine, leucine, isoleucine and parin so that the EAA NEAA ratio in the composition is about 0.50 to 3.50, preferably about 0.85 to 1.70. In addition to general foods, the composition of the present invention containing the active ingredient) may be additionally taken, or the EAA / NEAA ratio in the food ingredients may be within the above range. By ingesting the designed food of the present invention, the present invention is safe and maximizes its effectiveness. The latter, when the EAA _/ ^/ NEAA ratio in food ingredients ingests food of the present invention designed to be within the range of the ratio is, the amino acids from amino acids and proteins that is part of the food product, the additional Designed so that the EAA / NEAA ratio for the total amount of lysine, threonine, leucine, isoloicin, and valine formulated together is about 0.50 to 3.50, preferably about 0.85 to about I.70 To do.

Glyposome biosynthesis control gene expression inhibitor> The lipid biosynthesis control gene expression inhibitor of the present invention is an expression inhibitor of a gene controlling lipid biosynthesis, characterized by containing lysine, threonine, leucine, isoleucine and parin as active ingredients.

 In the lipid biosynthesis control gene expression inhibitor of the present invention, the molar composition ratio (%) of each amino acid to all amino acids is lysine 5.0 or more to less than 65.0, threonine 5.0 or more to 65 5 Less than 0, Leucine 1. 0 to less than 35.0, Isoleucine 1. 0 to less than 35.0, Phosphorus 1. 0 to less than 35.0. Preferably, lysine 1 5. 0 to less than 45.0, threonine 10.0 to less than 45.0, leucine 1 5. 0 to less than 35.0, isoleucine 1 0. 0 to less than 20.0 , Phosphorus, range from 10.0 to less than 2: 0. '

 The inhibitor of the present invention is a gene expression level of SREBP 1 c that controls fatty acid biosynthesis in the liver, a gene group of fatty acid biosynthetic enzymes such as FAS and ACL, and genes related to cholesterol biosynthesis in the liver. It is possible to suppress the gene expression level of a certain 3-Hydroxy-3-methylgutaryl-CoA synthase 1 (hereinafter, HMGCAS 1) under conditions of high fat diet intake. As a result, an increase in visceral fat weight induced by an increase in dietary fat intake due to intake of a high fat diet or the like, and in particular, an increase in lipid content in the liver can be suppressed.

 In addition, the composition of the present invention can activate AMP activated protein kinase (AMPK) in skeletal muscle and increase energy consumption in skeletal muscle. Example

 Hereinafter, examples and experimental examples will be given to describe the present invention in detail, but the present invention is not limited to these examples.

Example 1

According to the diet composition shown in Table 1, a group containing 7% (hereinafter referred to as weight%) lard (hereinafter referred to as STD group), a group containing 30% lard (hereinafter referred to as HFD group), and 30% —In addition to lysine, lysine, threonine, leucine, isoleucine and valine total 2% (hereinafter referred to as 2% EAAZHFD group), 4% (hereinafter referred to as 4% EAA / HFD group), 8% (hereinafter referred to as 8%) EAA / HFD group), 1 5% (hereinafter referred to as 1 2% EAA ZHFD group) In addition to 15% casein used as protein source, the prepared diet was ingested by C 5 7 B 6 mice for 8 weeks I let you. At this time, in order to match the total amount of casein added as a protein source and the free amino acid, the amino acid composition prepared based on the amino acid composition of casein is the sum of amino acid compositions other than casein and casein. 2 Corrected to 3%. For the 1 2% EAAZHFD group, the casein content was set to 11%. In addition to 30% lard, all groups ingesting diets containing a high content of lysine, threonine, leucine, isoleucine and valine are designated as EA AZHFD groups.

table 1

 Diet composition used in the test

 HF0 + EAA

 STD HFD

 Diet 2% EAA 4¾ EAA S% EAA 12¾ EM g / 100 g.

Cornstarch ⁸ 37.6 20.3 20.3 20.3 20.3 20.3 Casein ⁸ 15 15 15 15 15 1 1 Amino acid mixture based on casein composition ^b 8 8 6 4--Li'non hydrochloride 0.50 1.0 2.0 3.0 Threonine 0.50 1.0 2.0 3.0 Leucine 0.50 1.0 2.0 3.0 Isoloisin 0.25 0.5 1.0 1.5 heparin 0.25 0.5 1.0 1.5 alpha-cornstarch - 12.5 6.7 6.7 6.7 6.7 6.7 Sho耱^a 10 10 10 10 10 10 lard 7 30 30 30 30 30 cellulose ⁸ 5 5 5 5 5 5 vitamin mixture ^beta 1.25 1.25 1.25 1.25 1.25 1.25 Mineral mixture ^β 3.5 3.5 3.5 3.5 3.5 3.5

L-cystine 0.225 0.225 0.225 0.225 0.225 0.225 added ΕΑΑ, S 100 g ^c -2 4 8 12 Total amino acid, s ioo g ^d 23 23 23 23 23 23

EAA / NEAA ratio 0. 71 0.71 0.SS 1.09 1.69 2.71 Energy. Kcal / 100g 355.1 470.1 470.1 470.1 470.1 470.1 Lipid energy,% 1 7.7 57.4 57.4 57.4 57.4 57.4 a. Diet is slightly based on AIN-9 G composition It was prepared with the following improvements.

b. Amino acid compounds based on casein composition contain: 2.5% His, 4.5% Phe, 8.8% Hys-HCl, 1.1% Trp, 3.8% Thr, 2. 4% Met, 4.5% l ie, 5. 7% Val

8. 1% Leu, 9.4% Pro, 9.4% Asn. H ₂ 0, 4. 9% Tyr, 2. 6% Ala, 3.3% Arg, 5. 1% Ser, 9. 2% Gin, 1.6% Gly, 0.5% Cyst ine, 3.2% Asp and 6.2% starch.

c. EA A added represents the total of lysine hydrochloride, threonine, leucine, isoleucine and parin added in addition to casein and amino acid mixtures based on casein composition.

d. Total amino acid represents the sum of casein, amino acid mixture based on casein composition and the amount of EAA added. Result 1: Body weight, organ weight, blood biochemistry parameters

At the time when the diet shown in Table 1 was ingested for 8 weeks, an autopsy was performed, and body weight, organ weight, and blood biochemical parameters were measured. The results are shown in Table 2. In EAA / HFD, it was found that the increase in body weight, fat weight, blood insulin concentration, blood levtin concentration, and blood cholesterol concentration that increase in the HFD group with the increase in intake of essential amino acids can be significantly suppressed. It was. In addition, the increase in liver weight and kidney weight observed when a large amount of amino acid or protein was ingested at this time was not observed, indicating that these were not toxic.

Table 2 Body weight, organ weight, blood biochemical parameters of C 57 B 6 mice at 8 weeks after ingestion

Diet STD HFD 2% EAA / HFD 4¾ EAA HFD 6% EM / HFO 1Z% EAA / HFD n-9 n-9 η9 i 9 n-9 n-9 Weight gain g S.2 or 1.7 ⁶ '13.4 t, .7 ^a 13.3 t 3.8 ^a 11.8 i 1.7 ^a 10.4 t 1.7 ^ab 7.3 ± 1.6 ^C meal) 1 intake S. kcal / day 4.1 1 0.6 3.4 ± 0.2 3.6 t 0.2 3.5 t OJ 3.5 t OA 3.4 0.3 White fat. g 1.5 1 3.7 i 0.5 ^a 3.3 ± a ' ^b 2.7 1 OS ^a ' ^b 2.6 t 0.6 ^{b <c} 1.5 ± 0A ^a Liver K. g 1.2 t 0.1 ^a 1.3 ± 0.1 ^b 1.3 ± 0.2 ^ab 1.3 or 0.1 ^b 1.1 t 0.1 ^b 1.0 t 0.1 ^b ab

g 0.33 ± 0.01 0.33 t 0.02 ^a ' ^b 0.34 ± 0.01 ^ab 0.35 or 0.03 ^a 0.33 t 0.01 ^ab 0.32 t 0.0 Muscle.g 0.33 t 0.02 0.32 t 0.01 0.33 1 0.01 0.34 t 0.03 0.32 t 0.01 0.32 t 0.02 Mg / dl 72 1 17 70 t 10 65 or 12 77 ± 31 64 t 8 58 t 10 Free fatty acid. Mm ₀ l / l 0.48 or 0.0 ^a 0.38 t 0.1 ^b 0.35 t 0.1 ^b 0.37 or 0.1 ^b 0.38 t 0.1 ^b 0.38 or 0.1 ^b Colles 亍 roll. mg / dl 117 or 15 ^£ 1 »t 18 ^a 145 ± 22 ^ab 132 or 15 ^bc 128 t 15 111 t 13 ^c

₂₄ a, b Glucose, mg / dl 212 t 31 ^a 254 '21 ^b 245 t 25 ^ab 230 t 31 ^ab 2 7 ± 34 ^a ' ^b 223 t facetate. Imol ha 144 or 11 131 ± B 133 t 8 136 t 17 137 t 11 133 t 8 -ΟΗ-Butley μηο \ / \ 203 t 93 185 or 60 167 ±-48 192 ± 96 249 t 100 255 t 68 Insulin. Ng / inl 0.6 6.3 "2.7 or. (B ^a ' ^b 3.9 t 3.7 ^a 2.1 ± 0.9 ^a ' ^b 1.6 t o. » ^ab 0.9 t 0, production leptin.ng/ml 4.3 to t.1 ^bc 40.5 to 26.9 ^a 31.5 t 20.9 ^ab 14.2 ± I0.7 * ' ^c 13.3 t 10.1 ^{b, <} 2.6 t 1.4 ^e Data represent mean soil standard deviation.

There is a significant difference in mean values between experimental groups that do not have the same alphabet. p <0.05 (Tukey HSD)

Result 2: Gene expression level

 Table 3 shows the gene expression levels of genes related to lipid biosynthesis in the liver (SREB Plc gene, HMGCAS1 gene, ACL gene and FAS gene) at the time when the diet of Table 1 was ingested for 8 weeks. In 8% E AAZHFD, it was found that the gene expression levels of SREBP 1 c and HMGCAS 1 increased in the HFD group could be significantly suppressed. It was also found that the expression of genes related to fatty acid biosynthesis such as FAS and ACL can be significantly reduced. Regarding SREB P 1 c, it became clear that the gene expression level can be suppressed depending on the increase in the intake of essential amino acids (Fig. 1A).

In addition, it was confirmed that AMP-activated protein kinase (hereinafter referred to as AM PK) in skeletal muscle increased, even in the 8% EA / HFD group. B) It has been found that energy consumption in skeletal muscle can be increased.

Table 3 Gene expression level in C 57 B 6 mouse liver at 8 weeks after ingestion

―, Group

_STD HFD i% EAA / HFD

ACL ATP citrate lyase 1.00 t 0,2 0. & 6 ± 0.20 ^a 0.54 0.12 ^b

HMOCAS 1 3-hydroxy-3-methylglutaryl-CoA synthase 1 1.00 ±. 0.29 ^b 1.53 ± 0.25 ^a 0.90 ± 0.34 ^b

FAS β-fatty acid synthase 1.00 ± 0.3β ³ 0.83 ± 0.24 ³ Q.4 * O.I4 ^b -α α-node Node-binding protein 1 c 1.00 * 0.21 ^ab 1.66 ± 0.60 ^a 0.77 or 0.49 ^b Relative amount of mRNA Is normalized by the amount of 18 S ribosomal RNA.

 Data represent mean soil standard deviation.

There is a significant difference in the mean values between experimental groups that do not have the same alphabet. p 〈0.05 (Tukey HSD)

Result 3: Lipid content and fatty acid composition

Table 4 shows the lipid content and fatty acid composition in the liver when the diet of Table 1 was ingested for 8 weeks. In 8% EAAZHFD, it became clear that the total fat content (total lipid) and triglyceride content increased in the HFD group can be significantly reduced. It was also found that the content of monounsaturated fatty acids (MUFA) such as oleic acid contained in large amounts in lard can be significantly reduced.

Table 4 Lipid content and fatty acid composition in the liver of C 5 7 B 6 mice at 8 weeks after ingestion

 8

 Do

 STD HFD 8¾ ΕΑΛ / HFD

 rv-9 n-9

 ¾

C14: 0 0.42 0. 8 ^a 0.34 ± 0.05 "0.20 1 0.12"

C16: 0 26.5 26.4 0.6 "2b.O t 0.3 ^ab 25.4 1 1.2"

C16: 1 5.9 0.fi ^a 3.1 i 0.4 ^b 1.9 ± 0.9 ^C

C18: 0 12.1 6.6 1.7 ^b 6.5 t 1.3 ^b 10.0 ± 3., ^a

C18: 1 ln-9) 42.5 42.5 3.8 '41.9 1 2.8 ^B 35.1 1 6.9 ^b

CI 8: 2 | n-6) 9.8 7.4 1.4 ^a 12.2 1 0.8 "14.0 or 0.8"

 C20: 0 0.2 0.79 0.39 0.76 ± 0.11 0.31 t 0.2 &

 C20: 1 ln-9) 0.6 0.33 0.25 0.05 l 0.W H.D.

 C20: 2 N.D. 0.34 0.26 0.06 ± 0.t0 0.02 1 0.05

oo C20: 3 in-6) N.D. 0.69 0.30 0.72 1 0.13 0.63 ± 0.26

 C20: 4 fn-6) 0.3 6.4 1.8 6.0 i 0.8 9.0 i 2.7

 C20: 5 ln-3) N.D. 0.26 0.22 0.20 t 0.12 0.17 ± 0.14

C22: 6 ln-3) ND Ι.β 0.4 ^b 2.2 i 0.3 ^b 3.2 1 1.4 ^a

MUFA total.% 46.8 4B.4 45,0 37.0 1 6.8 ^b

27.1 1 4.7° PUFA total.% 10.8 16.9 21.3

27.1 1 4.7 °

n-3 needle.% 0.7 2.1 2.4 ± 0.3 ^ab 3.4 1 1.5 "

n-6 needle.% 10.1 14.5 1S.9 i 1.6 "23.6 t 3.4 ^a needle.« In-weaving mg g «4.4 17. 105.7 i 20.2 77-5 t 13.6

Triglycerides. Medium mg g 49.1 4 o 3317.3 ^a 46.8 t 14. <»32-0 ± 12.3

 Cholesterol. Pair | ¾ me g 15.5 2.2 16.6 ± 2.4 15.7 3.2

 Data represent mean soil standard deviation.

There is a significant difference in the mean values of the experimental groups that do not have the same alphabet. p <0. 05 (Tukey HSD) ND: Not determined

Result 4: Liver observation

 Typical liver tissue slices in the HFD group and 8% E AAZHFD group when the diet of Table 1 was ingested for 8 weeks are shown (Fig. 2). As a result, it was found that lipid droplets and fatty degeneration were significantly suppressed in the δ HFD group.

Example 2

 A diet consisting of STD, HFD, and 8% EAA / HFD in Table 1 was fed to ob / ob mice for 2 weeks. As a result, GOT (glutamate oxalate acetic acid transaminase) and GPT (Daltamate pyruvate transaminase), which are markers of hepatitis, decrease as well as significant improvement of fatty liver. It was found to be effective for hepatitis (Fig. 3). The ob and ob mice are commonly used as experimental models for non-alcoholic fatty liver. Comparative Example 1

 Based on the diet composition shown in Table 1, in addition to 30% lard (hereinafter referred to as HFD group), 30% lard, lysine, threonine, leucine, isoleucine and valine total 6% (hereinafter referred to as EAAZHFD group), a group in which 1% of proline which is a non-essential amino acid is added to 6% in total of lysine, threonine, leucine, isoleucine and parin (hereinafter referred to as EAA + Pro / HFD group), C 57 B 6 mice were ingested for 2 weeks with a diet prepared so that 2% glycine was added (hereinafter referred to as EAA + G 1 y / HFD group), and the effects of non-essential amino acids were observed. As a result, as shown in Fig. 4A, the inhibitory effect of lysine, threonine, leucine, isoleucine, and parin on the body weight gain phenomenon caused by ingestion of a high-fat diet can be inhibited by simultaneous intake of glycine or proline. all right.

Comparative Example 2

Based on the diet composition shown in Table 1, in addition to the group containing 7% lard (hereinafter referred to as STD group), the group containing 30% lard (hereinafter referred to as HFD group) and 30% lard, lysine and threonine , Leucine, isoleucine and valine total 8% (hereinafter referred to as EAA / H FD group), lysine, threonine, leucine, isoleucine and parin C 57 B 6 mice were ingested for 2 months with a diet prepared to add 6% to a total of 2% arginine, a non-essential amino acid (hereinafter referred to as EAA + ArgZHFD group). The effects of amino acids were observed. As a result, as shown in Figure 4B, the increase in adipose tissue weight due to the intake of a high-fat diet is suppressed by the intake of lysine, threshnin, leucine, isoleucine, and parin. It was found that this effect attenuated.

Comparative Example 3

 'Based on the diet composition shown in Table 1, a group containing 30% lard (hereinafter referred to as HFD group), in addition to 30% lard, lysine, threonine, leucine, isoleucine and valine total 8% In addition, lysine, threonine, leucine, isoloicin, and valine total 6% plus 2% non-essential amino acid arginine (hereinafter referred to as EAA + A rg / HFD group), etc. The C5 7 B 6 mice were ingested for 2 months with a diet prepared to add 2% glycine to the group (hereinafter referred to as EAA + G 1 y / HFD group), and the effects of non-essential amino acids were observed. . As a result, as shown in Figure 4C, arginine or glycine was taken at the same time as the intake of lysine, threonine, leucine, isoleucine, and parin against the increase in blood total cholesterol level due to high fat diet. It was found to be inhibited by doing.

Example 3

 The composition range of each amino acid when a composition containing lysine, threonine, leucine, isoleucine, and valine exerts anti-obesity, anti-hyperlipidemia, and anti-fatty liver effects was evaluated as follows. .

1

Based on the diet composition shown in Table 1, Table 5 shows lysine, threonine, leucine, isoleucine and valine in addition to 30% lard (hereinafter referred to as HFD group), 30% lard. 4 Diet prepared so that the total composition would be 8% (EAA / HFD group, EAA-B / HFD group, EAA-K / HFD group, EAA—T / HFD group) were ingested by C 57 B 6 mice for 8 weeks, and the blending ratios of five types of amino acids and their effects were observed. In addition, the £ 8 //? 1? 0 group has the same bait composition as the 8% £ 8A group in Table 1. As a result, the group that ingested diets containing EAA in four different compositions, as shown in Figure 5A F, showed a significant increase in body weight gain, total fat weight, and body fat mass. It was revealed that hepatic triglycerides and hepatic total cholesterol were significantly decreased or tended to decrease compared to the HFD group. Table 5 Composition of amino acids used in the study

 EAA EAA-B EAA-K EAA-T

 Molar ratio (%, mol / mol)

 Linn hydrochloric acid 17.6 20 30 20

 Thread Nin 32.0 20 20 40

 Isoleucine 12.2 15 12.5 10

 Palin 13.7 15 12.5 10

 Leucine 24.5 30 25 20

Based on the diet composition shown in Table 1, in addition to 30% lard (hereinafter referred to as HFD group), 30% lard, lysine, threonine, leucine, isoleucine and valine are shown in Table 6 3 Eight weeks of C 57 B 6 mice with diets prepared to a total of 8% for each type of composition (each, EAAZHFD group, EAA—K 60, HFD group, EAA—Τ 60 / HFD group) We ingested and observed the blending ratio of 5 kinds of amino acids and their effects. The EAAZHFD group has the same feed composition as the 8% EAA group in Table 1. As a result, as shown in Fig. 6A D, the group that ingested the diet containing EAA in three types of composition, as shown in Fig. 6A D, blood levtin concentration, blood cholesterol concentration, and It was revealed that liver weight was significantly reduced or tended to decrease compared to the HFD group. Amino acid composition used in the test

 ―,, EAA EAA-K60 EAA-T60

 Molar ratio (% .mol / mol)

 Glycine hydrochloride 17.6 60 20

 Thread Nin 32.0 20 60

 Isoleucine 12.2 5 5

 Palin 13.7 5 5

 Leucine 24.5 10 10

Example 4

 When a composition containing lysine, threonine, leucine, isoleucine, and valine exerts an anti-fatty liver effect, the composition range of each amino acid is determined using ob / ob mice, which are non-alcoholic fatty liver model mice. And evaluated.

 Fj; ll: 丄

 Based on the diet composition shown in Table 1, Table 5 shows lysine, threonine, leucine, isoleucine and valine in addition to 30% lard (hereinafter referred to as HFD group), 30% lard. 4 Ob diet mice prepared with a total composition of 8% (EAA / HFD group, EAA—BZHFD group, EAA—K ^ HFD group, EAA—TZHFD group) Ingested for 2 weeks, the mixing ratio of 5 types of amino acids and their effects were observed. As a result, as shown in Figs. It has become clear that there is a decrease or a tendency to decrease.

 B;

Based on the diet composition shown in Table 1, in addition to 30% lard (hereinafter referred to as HFD group), 30% lard, lysine, threonine, leucine, isoleucine, and valine were added to EAA in Table 6. — Ob / ob mice with diets prepared to reach a total of 8% with the composition shown as K 60 and EAA— T 60 (each, E AA—K 60 HFD group, EAA — T60 / HFD group) Ingested for 2 weeks, 5 amino acids The mixing ratio and the effect were observed. As a result, as shown in Figures 8A and B, it was clear that in the group that took EAA-containing food, liver weight and triglyceride in the liver were significantly lower or tended to decrease compared to the HFD group. Became. Industrial applicability

 The composition containing lysine, threonine, leucine, isoleucine and parin provided by the present invention suppresses fatty liver and steatohepatitis. The composition for anti-fatty liver and steatohepatitis of the present invention is particularly effective in steatohepatitis and steatohepatitis caused by ingestion of a high fat diet. Further, the invention is characterized in that it contains lysine, threonine, leucine, isoleucine and valine provided by the present invention, and does not contain at least one non-essential amino acid selected from proline, dalysin, tyrosine and arginine. The composition is useful for anti-obesity and anti-hyperlipidemia. Furthermore, since the composition of the present invention comprises an amino acid as an active ingredient, it is highly safe and has few side effects. Therefore, the composition of the present invention can be administered for a long period of time. In fatty liver, steatohepatitis, obesity and hyperlipidemia It can be used advantageously for prevention, treatment and improvement. The lipid biosynthesis regulating gene expression inhibitor of the present invention can be used as an experimental reagent in the fields of physiology and biochemistry in addition to its use as a medicament as described above. While some of the specific embodiments of the present invention have been described in detail, those skilled in the art will recognize that the specific embodiments shown are subject to various modifications without departing substantially from the teachings and advantages of the present invention. Modifications and changes can be made. Accordingly, all such modifications and changes are intended to be included within the spirit and scope of the invention as claimed in the following claims. This application is based on Japanese Patent Application No. 2 0 0 5-3 1 3 3 4 6 filed in Japan, the contents of which are incorporated in full herein.

Claims

 The scope of the claims 1. Lysine, threonine, leucine, isoleucine and valine as molar constituent ratios with respect to all amino acids in the composition, lysine 5.0% to less than 65.0%, threonine 5.0% to 65.0% less than, leucine 1.0% or more and 35. ^non-zero /. Less than, isoleucine 1.0% or more to less than 35.0% and parin 1.0% or more to less than 35.0%.  2. The composition according to claim 1, wherein the fatty liver is fatty liver induced by intake of a high fat diet. 3. Lysine, threonine, leucine, isoleucine and valine as molar constituent ratios with respect to all amino acids in the composition, respectively, lysine 5.0% to less than 65.0%, threonine 5.0% to 65.0% Less than%, leucine 1% or more to less than 35.0%, isoleucine 1.0% or more to less than 35.0%, and parin 1.0% or more to less than 35.0%, and proline, An anti-obesity composition comprising no at least one non-essential amino acid selected from the group consisting of glycine, tyrosine and arginine.  4. Lysine, threonine, leucine, isoleucine and valine as molar constituent ratios with respect to all amino acids in the composition, respectively, lysine 5.0% to less than 65.0%, threonine 5.0% to 65.0% Less than, Leucine 1. 0% to less than 35.0%, Isoleucine 1. 0% to less than 35.0% and Palin 1. Antihyperlipidemic, characterized by containing 0% or more and less than 35.0% and not containing at least one non-essential amino acid selected from the group consisting of proline, glycine, tyrosine and arginine Syndrome composition. 5. The lysine, threonine, leucine, isoleucine and valine are contained so that the essential amino acid non-essential amino acid ratio in the composition is 0.550 to 3.50 in molar ratio. The composition according to any one of 4 to 4. 6. Lysine, threonine, leucine, isoleucine and valine as molar constituent ratios of all amino acids in pharmaceuticals, respectively, lysine 5.0% to less than 65.0%, threonine 5.0% to 65.0 Less than%, leucine 1. 0% to less than 35.0%, isoleucine 1. 0% to less than 35.0% and parin 1. 0% to 35. Medicine for liver or anti steatohepatitis.  7. Lysine, threonine, leucine, isoleucine, and valine are each included in a molar ratio of lysine 5.0% to 65. ◦ Less than%, Threonine 5.0% or more to less than 65.0%, Leucine 1.0% or more to less than 35.0%, Isoleucine 1.0% or more to less than 35.0% or Palin 1.0% or more Food and drink for prevention or improvement of fatty liver or steatohepatitis, containing in a range of ˜35.0% or less. '  8. Lysine, 'threonine, leucine, isoleucine and valine as molar constituent ratios to all amino acids in the drug, lysine 5.0% to less than 65.0%, threonine 5.0% to 65.0% Less than, leucine 1.0% or more to less than 35.0%, isoleucine 1.0% or more to 35.0 ° /. And at least one non-essential amino acid selected from the group consisting of proline, glycine, tyrosine and arginine, and not more than 1.0% and less than 35.0%. An anti-obesity drug.  9. Lysine, threonine, leucine, isoleucine, and valine are each included in a molar ratio of lysine 5.0% to 65. Less than 0%, Threonine 5.0% or more to less than 65.0%, Leucine 1.0% or more to 35.0% Not yet found, Isoleucine 1.0% or more to less than 35.0% and Palin 1.0% or more For preventing or ameliorating obesity, characterized in that it contains less than 35.0% and does not contain at least one non-essential amino acid selected from the group consisting of proline, glycine, tyrosine and arginine Food and drink. 10. Lysine, threonine, leucine, isoleucine and valine as molar constituent ratios for all amino acids in pharmaceuticals, respectively, lysine 5.0% or more to 65. Less than 0%, Threonine 5.0% or more to less than 65.0%, Leucine 1.0% or more to less than 35.0%, Isoleucine 1.0% or more to less than 35.0% or Palin 1.0% or more 35, less than 0%, and does not contain at least one non-essential amino acid selected from the group consisting of proline, glycine, tyrosine and arginine, for antihyperlipidemia Medicine.  1 1. Lysine, threonine, leucine, isoleucine, and valine as molar constituent ratios of all amino acids in food and drink, lysine 5.0% to less than 65.0%, threonine 5.0% to 65.0% Less than%, leucine 1. 0% to less than 35.0%, isoleucine 1. 0% to less than 35.0% and parin 1. 0% to less than 35.0%, and proline. A food or drink for preventing or improving hyperlipidemia, characterized by not containing at least one non-essential amino acid selected from the group consisting of glycine, tyrosine and arginine.  1 2. Lysine, threonine, leucine, isoleucine, and valine, phosphorus as molar constituent ratios with respect to all amino acids in the agent, lysine 5.0% to less than 65.0%, threonine 5.0% to 65%. Less than 0%, leucine 1.0% or more to 35.0% not yet found, isoleucine 1.0% or more to less than 35.0% and valine 1.0% or more to less than 35.0%, lipids Biosynthesis control gene expression inhibitor.  1 3. The inhibitor according to claim 12, wherein the lipid biosynthesis control gene is SREB P 1 c gene, HMGCAS 1 gene, ACL gene or F AS gene.  14. Lysine, threonine, leucine, isoleucine and valine as molar constituent ratios with respect to all amino acids in the composition, lysine 5.0% to less than 65.0%, threonine 5.0% to 65.0% A composition containing less than%, leucine 1.0% to less than 35.0%, isoleucine 1.0% to less than 35.0%, and valine 1.0% to less than 35.0%. 1 5. Lysine, threonine, leucine, isoleucine, and valine as molar ratios to all amino acids in the composition, respectively, lysine 5.0% to less than 65.0%, threonine 5.0% to 65%. Less than 0%, Leucine 1. 0% or more Less than 35.0%, Isoleucine 1. 0% to less than 35.0% and Parin 1. More than 0% to less than 35.0%, and selected from the group consisting of proline, glycine, tyrosine and arginine A composition characterized in that it does not contain at least one non-essential amino acid.  1 6. The lysine, threonine, leucine, isoleucine and valine are contained so that the essential amino acid non-essential amino acid ratio in the composition is 0.50 to 3.50 in molar ratio. 14. The composition according to 14 or 15.  1 7.Molar composition ratio of lysine, threonine, leucine, isoleucine and valine to the total amino acids in the composition is lysine 5.0% to less than 65.0%, threonine 5.0% to 65%. Less than 0%, Leucine 1., 0% or more to less than 35.0%, Isoleucine 1. 0% or more to less than 35.0% and Parine 1. 0% or more to less than 35.0% A method for preventing or treating fatty liver or steatohepatitis, comprising administering a product to an administration subject.  1 8. Lysine, threonine, leucine, isoleucine, and valine are each included in a molar ratio of lysine 5.0% to 65. Less than 0%, Threonine 5.0% or more to less than 65.0%, Leucine 1.0% or more to less than 35.0%, Isoleucine 1.0% or more to less than 35.0% or Palin 1.0% or more 35. A composition containing less than 0% and not containing at least one non-essential amino acid selected from the group consisting of proline, glycine, tyrosine and arginine is administered to a subject. A method for preventing or treating obesity. 1 9.Lysine, threonine, leucine, isoleucine and valine as molar constituent ratios with respect to all amino acids in the composition, respectively, lysine 5.0% to less than 65.0%, threonine 5.0% to 65%. Less than 0%, leucine 1.0% or more to less than 35.0%, isoleucine 1.0% or more to less than 35.0%, and valine content in the range of 0% to less than 35.0%, and proline, At least one non-essential amino acid selected from the group consisting of glycine, tyrosine and arginine. A method for preventing or treating hyperlipidemia, comprising administering a composition that does not have to a subject.  20. Lysine, threonine, leucine, isoleucine and valine as molar constituent ratios with respect to all amino acids in the agent, lysine 5.0% to less than 65.0%, threonine 5.0% to less than 65.0% Leucine 1.0% to less than 35.0%, isoleucine 1.0% to less than 35.0% and parin 1.0% to less than 35.0%. A method for suppressing lipid biosynthesis control gene expression, comprising administering.  2 1. The molar composition ratio of all amino acids in the composition is lysine 5.0% to less than 65.0%, threonine 5.0% to less than 65.0%, oral isine 1.0% or more Manufactured an anti-fatty liver or anti-fatty hepatitis composition containing less than 35.0%, isoleucine from 1.0% to less than 35.0% and valine from 1.0% to less than 35.0% Use of lysine, threonine, leucine, isotocin and parin. 22. The molar composition ratio of all amino acids in the composition is lysine 5.0% to less than 65.0%, threonine 5.0% to less than 65.0%, oral isine 1.0% or more Less than 35.0%, isoleucine 1.0% to less than 35.0% and valine 1.0% to 35.0%. Lysine, threonine, leucine, for producing an anti-obesity composition that is contained in a range of less than and does not contain at least one essential amino acid selected from the group consisting of proline, glycine, tyrosine and arginine Use of isoleucine and parin. 23. As a molar composition ratio with respect to all amino acids in the composition, lysine 5.0% or more to less than 65.0%, threonine 5.0% or more to less than 65.0%, oral isine 1.0% or more From the group consisting of proline, glycine, tyrosine and arginine, containing less than 35.0%, isoleucine from 1.0% to less than 35.0% and parin from 1.0% to less than 35.0% At least one required Use of lysine, threonine, leucine, isoleucine and parin for the production of an antihyperlipidemic composition free of amino acids.  24. The molar composition ratio of all amino acids in the preparation is lysine 5.0% to less than 65.0%, threonine 5.0% to less than 65.0%, leucine 1.0% to 35.0% % Lysine, isoleucine 1.0% to less than 35.0% and valine lysine for producing a lipid biosynthesis control gene expression inhibitor containing 1.0% to less than 35.0% Use of threonine, leucine, isoleucine and valine.