Inhibiting effect of water extract of algae belonging to genus nannochloropsis on weight gain

Abstract

The invention provides a novel application of nannochloropsis algae. Specifically, an aqueous extract of an algae belonging to the genus Nannochloropsis is used to inhibit weight gain or to block the promotion of cholesterol synthesis.

Description

Technical Field

[0001] The present invention relates to a weight gain inhibitor, a food or beverage for inhibiting weight gain, a blocker for promoting cholesterol synthesis, a food or beverage for blocking promoting cholesterol synthesis, and a pharmaceutical composition for treating diseases associated with promoting cholesterol synthesis, characterized in that the composition contains a water extract of algae of the genus Nannochloropsis as an active ingredient. Background Art

[0002] Extracts of Nannochloropsis algae are known to have various physiological activities.

[0003] Patent Document 1 describes that a hydrous ethanol extract of Nannochloropsis algae has anti-inflammatory activity.

[0004] Patent Document 2 describes that an extract of Nannochloropsis algae can increase the activity of paraoxonase 1 (PON1) that inhibits the oxidation of low-density lipoprotein (LDL).

[0005] Non-Patent Document 1 describes that a substance isolated from algae of the genus Nannochloropsis can improve the function of high-density lipoprotein (HDL).

[0006] Prior art literature

[0007] Patent Literature

[0008] Patent Document 1: Japanese Patent Application Publication No. 2015-174850

[0009] Patent Document 2: International Publication No. WO2019 / 026067

[0010] Non-patent literature

[0011] Non-patent literature 1: BioFactors.2020;46:146-157 Summary of the invention

[0012] Problems to be solved by the invention

[0013] The present invention focuses on Nannochloropsis algae as a raw material for health foods and the like, and sets as an object to provide a new use thereof.

[0014] Technical solutions to solve problems

[0015] After intensive research on this topic, the inventors found that the water extract of Nannochloropsis algae can inhibit weight gain and further block the promotion of cholesterol synthesis. The present invention was completed based on the above findings.

[0016] That is, the present invention relates to the following contents [1] to

[25] .

[0017] [1] A weight gain inhibitor comprising a water extract of algae belonging to the genus Nannochloropsis as an active ingredient.

[0018] [2] The inhibitor according to [1] above, wherein the water extract contains one or more compounds selected from the following [Group A]:

[0019] 〔Group A〕

[0020] 15-HEPE;

[0021] Monoacylglycerol trimethyl homoserine represented by general formula (I);

[0022] [Chemical formula 1]

[0023]

[0024] Wherein, R1 and R2 are the following combinations A, B, E or F:

[0025] combination <![CDATA[R1]]> <![CDATA[R2]]> A Hydroxyeicosapentaenoic acid (HEPE) residue hydrogen B hydrogen HEPE residue E Eicosapentaenoic acid (EPA) residues hydrogen F hydrogen EPA residue

[0026] as well as

[0027] Lysophosphatidylcholine represented by general formula (II),

[0028] [Chemical formula 2]

[0029]

[0030] Wherein, R1 and R2 are the following combinations A or B:

[0031] combination <![CDATA[R1]]> <![CDATA[R2]]> A HEPE residue hydrogen B hydrogen HEPE residues.

[0032] [3] The inhibitor according to [2] above, wherein the water extract further contains one or more compounds selected from the following [Group B]:

[0033] [Group B]

[0034] 13-HOTrE;

[0035] 13-HODE;

[0036] 15-HETrE;

[0037] 15-HETE;

[0038] Monoacylglycerol trimethyl homoserine represented by general formula (I);

[0039] Wherein, R1 and R2 are the following combinations C or D:

[0040] combination <![CDATA[R1]]> <![CDATA[R2]]> C Hydroxyeicosatetraenoic acid (HETE) residues hydrogen D hydrogen HETE residues

[0041] as well as

[0042] Lysophosphatidylcholine represented by general formula (II),

[0043] Where R1 and R2 are combination C or D:

[0044] combination <![CDATA[R1]]> <![CDATA[R2]]> C Hydroxyperoxyeicosapentaenoic acid (HpEPE) residue hydrogen D hydrogen HpEPE residues.

[0045] [4] The inhibitor according to [1] above, wherein the algae of the genus Nannochloropsis is Nannochloropsis oceanica.

[0046] [5] The inhibitor according to [1] above, which inhibits weight gain caused by ingestion of a high-fat diet.

[0047] [6] A food or beverage for suppressing weight gain, comprising a water extract of algae belonging to the genus Nannochloropsis as an active ingredient.

[0048] [7] The food or beverage according to [6] above, wherein the water extract contains one or more compounds selected from the following [Group A]:

[0049] 〔Group A〕

[0050] 15-HEPE;

[0051] Monoacylglycerol trimethyl homoserine represented by general formula (I);

[0052] [Chemical formula 3]

[0053]

[0054] Wherein, R1 and R2 are the following combinations A, B, E or F:

[0055] combination <![CDATA[R1]]> <![CDATA[R2]]> A Hydroxyeicosapentaenoic acid (HEPE) residue hydrogen B hydrogen HEPE residue E Eicosapentaenoic acid (EPA) residues hydrogen F hydrogen EPA residue

[0056] as well as

[0057] Lysophosphatidylcholine represented by general formula (II),

[0058] [Chemical formula 4]

[0059]

[0060] Wherein, R1 and R2 are the following combinations A or B:

[0061] combination <![CDATA[R1]]> <![CDATA[R2]]> A HEPE residue hydrogen B hydrogen HEPE residues.

[0062] [8] The food or beverage according to [7] above, wherein the water extract further contains one or more compounds selected from the following [Group B]:

[0063] [Group B]

[0064] 13-HOTrE;

[0065] 13-HODE;

[0066] 15-HETrE;

[0067] 15-HETE;

[0068] Monoacylglycerol trimethyl homoserine represented by general formula (I);

[0069] Wherein, R1 and R2 are the following combinations C or D:

[0070] combination <![CDATA[R1]]> <![CDATA[R2]]> C Hydroxyeicosatetraenoic acid (HETE) residues hydrogen D hydrogen HETE residues

[0071] as well as

[0072] Lysophosphatidylcholine represented by general formula (II),

[0073] Where R1 and R2 are combination C or D:

[0074] combination <![CDATA[R1]]> <![CDATA[R2]]> C Hydroxyperoxyeicosapentaenoic acid (HpEPE) residue hydrogen D hydrogen HpEPE residues.

[0075] [9] The food or drink according to [6] above, wherein the algae of the genus Nannochloropsis is Nannochloropsis oceanica.

[0076]

[10] The food or drink according to [6] above, which suppresses weight gain caused by ingestion of a high-fat meal.

[0077]

[11] A cholesterol synthesis inhibitor containing a water extract of algae of the genus Nannochloropsis as an active ingredient.

[0078]

[12] The blocking agent according to

[11] above, wherein the water extract contains one or more compounds selected from the following [Group A]:

[0079] 〔Group A〕

[0080] 15-HEPE;

[0081] Monoacylglycerol trimethyl homoserine represented by general formula (I);

[0082] [Chemical formula 5]

[0083]

[0084] Wherein, R1 and R2 are the following combinations A, B, E or F:

[0085] combination <![CDATA[R1]]> <![CDATA[R2]]> A Hydroxyeicosapentaenoic acid (HEPE) residue hydrogen B hydrogen HEPE residue E Eicosapentaenoic acid (EPA) residues hydrogen F hydrogen EPA residue

[0086] as well as

[0087] Lysophosphatidylcholine represented by general formula (II),

[0088] [Chemical formula 6]

[0089]

[0090] Wherein, R1 and R2 are the following combinations A or B:

[0091] combination <![CDATA[R1]]> <![CDATA[R2]]> A HEPE residue hydrogen B hydrogen HEPE residues.

[0092]

[13] The blocking agent according to

[12] above, wherein the water extract further contains one or more compounds selected from the following [Group B]:

[0093] [Group B]

[0094] 13-HOTrE;

[0095] 13-HODE;

[0096] 15-HETrE;

[0097] 15-HETE;

[0098] Monoacylglycerol trimethyl homoserine represented by general formula (I);

[0099] Wherein, R1 and R2 are the following combinations C or D:

[0100] combination <![CDATA[R1]]> <![CDATA[R2]]> C Hydroxyeicosatetraenoic acid (HETE) residues hydrogen D hydrogen HETE residues

[0101] as well as

[0102] Lysophosphatidylcholine represented by general formula (II),

[0103] Where R1 and R2 are combination C or D:

[0104] combination <![CDATA[R1]]> <![CDATA[R2]]> C Hydroxyperoxyeicosapentaenoic acid (HpEPE) residue hydrogen D hydrogen HpEPE residues.

[0105]

[14] The inhibitor according to

[11] above, wherein the algae of the genus Nannochloropsis is Nannochloropsis oceanica.

[0106]

[15] The inhibitor according to

[11] above, which blocks the promotion of cholesterol synthesis caused by the intake of high-fat food.

[0107]

[16] A food or beverage for blocking cholesterol synthesis, which contains a water extract of algae of the genus Nannochloropsis as an active ingredient.

[0108]

[17] The food or beverage according to

[16] above, wherein the water extract contains one or more compounds selected from the following [Group A]:

[0109] 〔Group A〕

[0110] 15-HEPE;

[0111] Monoacylglycerol trimethyl homoserine represented by general formula (I);

[0112] [Chemical formula 7]

[0113]

[0114] Wherein, R1 and R2 are the following combinations A, B, E or F:

[0115] combination <![CDATA[R1]]> <![CDATA[R2]]> A Hydroxyeicosapentaenoic acid (HEPE) residue hydrogen B hydrogen HEPE residue E Eicosapentaenoic acid (EPA) residues hydrogen F hydrogen EPA residue

[0116] as well as

[0117] Lysophosphatidylcholine represented by general formula (II),

[0118] [Chemical formula 8]

[0119]

[0120] Wherein, R1 and R2 are the following combinations A or B:

[0121] combination <![CDATA[R1]]> <![CDATA[R2]]> A HEPE residue hydrogen B hydrogen HEPE residues.

[0122]

[18] The food or beverage according to

[17] above, wherein the water extract further contains one or more compounds selected from the following [Group B]:

[0123] [Group B]

[0124] 13-HOTrE;

[0125] 13-HODE;

[0126] 15-HETrE;

[0127] 15-HETE;

[0128] Monoacylglycerol trimethyl homoserine represented by general formula (I);

[0129] Wherein, R1 and R2 are the following combinations C or D:

[0130] combination <![CDATA[R1]]> <![CDATA[R2]]> C Hydroxyeicosatetraenoic acid (HETE) residues hydrogen D hydrogen HETE residues

[0131] as well as

[0132] Lysophosphatidylcholine represented by general formula (II),

[0133] Where R1 and R2 are combination C or D:

[0134] combination <![CDATA[R1]]> <![CDATA[R2]]> C Hydroxyperoxyeicosapentaenoic acid (HpEPE) residue hydrogen D hydrogen HpEPE residues.

[0135]

[19] The food or drink according to

[16] above, wherein the algae of the genus Nannochloropsis is Nannochloropsis oceanica.

[0136]

[20] The food or drink according to

[16] above, which blocks the promotion of cholesterol synthesis caused by the intake of high-fat foods.

[0137]

[21] A pharmaceutical composition for treating a disease associated with the promotion of cholesterol synthesis, the pharmaceutical composition comprising an aqueous extract of algae of the genus Nannochloropsis as an active ingredient.

[0138]

[22] The pharmaceutical composition according to

[21] above, wherein the water extract contains one or more compounds selected from the following [Group A]:

[0139] 〔Group A〕

[0140] 15-HEPE;

[0141] Monoacylglycerol trimethyl homoserine represented by general formula (I);

[0142] [Chemical formula 9]

[0143]

[0144] Wherein, R1 and R2 are the following combinations A, B, E or F:

[0145] combination <![CDATA[R1]]> <![CDATA[R2]]> A Hydroxyeicosapentaenoic acid (HEPE) residue hydrogen B hydrogen HEPE residue E Eicosapentaenoic acid (EPA) residues hydrogen F hydrogen EPA residue

[0146] as well as

[0147] Lysophosphatidylcholine represented by general formula (II),

[0148] [Chemical formula 10]

[0149]

[0150] Wherein, R1 and R2 are the following combinations A or B:

[0151] combination <![CDATA[R1]]> <![CDATA[R2]]> A HEPE residue hydrogen B hydrogen HEPE residues.

[0152]

[23] The pharmaceutical composition according to

[22] above, wherein the water extract further contains one or more compounds selected from the following [Group B]:

[0153] [Group B]

[0154] 13-HOTrE;

[0155] 13-HODE;

[0156] 15-HETrE;

[0157] 15-HETE;

[0158] Monoacylglycerol trimethyl homoserine represented by general formula (I);

[0159] Wherein, R1 and R2 are the following combinations C or D:

[0160] combination <![CDATA[R1]]> <![CDATA[R2]]> C Hydroxyeicosatetraenoic acid (HETE) residues hydrogen D hydrogen HETE residues

[0161] as well as

[0162] Lysophosphatidylcholine represented by general formula (II),

[0163] Where R1 and R2 are combination C or D:

[0164] combination <![CDATA[R1]]> <![CDATA[R2]]> C Hydroxyperoxyeicosapentaenoic acid (HpEPE) residue hydrogen D hydrogen HpEPE residues.

[0165]

[24] The pharmaceutical composition according to

[21] above, wherein the algae of the genus Nannochloropsis is Nannochloropsis oceanica.

[0166]

[25] The pharmaceutical composition according to

[21] above, wherein the disease associated with the promotion of cholesterol synthesis is selected from the group consisting of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), dyslipidemia and metabolic syndrome.

[0167] Effects of the Invention

[0168] As described in the examples below, the water extract of Nannochloropsis algae can inhibit weight gain and block the promotion of cholesterol synthesis. The present invention using the water extract as an active ingredient can be used to treat diseases related to weight gain and promotion of cholesterol synthesis. BRIEF DESCRIPTION OF THE DRAWINGS

[0169] Figure 1 This is a box plot showing the distribution of the weight gain of each individual in each test group. ○: value of each individual. ×: average value. LFD: test group 1. HFD: test group 2. HFD+HL: test group 3. HFD+HH: test group 4.

[0170] Figure 2 This is a box plot showing the distribution of the weight gain rate of each individual in each test group (the base day is set to 1). ○: value of each individual. ×: average value. LFD: test group 1. HFD: test group 2. HFD+HL: test group 3. HFD+HH: test group 4. DETAILED DESCRIPTION

[0171] 〔Nannochloropsis algae〕

[0172] Nannochloropsis is a unicellular algae belonging to the phylum Anisochloropsis and class Eusomaphyceae.

[0173] There is no particular limitation on the use of algae belonging to the genus Nannochloropsis, and specific examples thereof include Nannochloropsis oceanica, Nannochloropsis oculata, Nannochloropsis gaditana, Nannochloropsis salina, Nannochloropsis atomus, Nannochloropsis maculata, Nannochloropsis granulata, and Nannochloropsis sp. Among them, Nannochloropsis oceanica and Nannochloropsis gaditana are preferred, and Nannochloropsis oceanica is particularly preferred.

[0174] Examples of Nannochloropsis oceanica include the NIES-2145 strain preserved in the National Institute for Environmental Studies (NIES collection) of Japan and the CCMP-1779 strain preserved in the NCMA (National Center for Marine Algae and Microbiota) (USA), and the NIES-2145 strain is preferred.

[0175] Algae of the genus Nannochloropsis can be obtained from microbial collections or markets, or can be isolated from nature.

[0176] The aqueous extract of the present invention may be prepared from one or more species of Nannochloropsis algae.

[0177] [Aqueous extract of Nannochloropsis algae]

[0178] There are no particular limitations on the aqueous extract of algae belonging to the genus Nannochloropsis (hereinafter also referred to as "algae aqueous extract"), and any aqueous extract can be used in the present invention.

[0179] In a preferred embodiment, the algae water extract contains one or more of the following compounds (1) to (7).

[0180] (1) Monoacylglyceryltrimethylhomoserine (MGTS) represented by the general formula (I):

[0181] [Chemical formula 11]

[0182]

[0183]

[0184] Wherein, R1 and R2 are any one of the following combinations A to F:

[0185] combination <![CDATA[R1]]> <![CDATA[R2]]> A Hydroxyeicosapentaenoic acid (HEPE) residue hydrogen B hydrogen HEPE residue C Hydroxyeicosatetraenoic acid (HETE) residues hydrogen D hydrogen HETE residues E Eicosapentaenoic acid (EPA) residues hydrogen F hydrogen EPA residue

[0186] The HEPE residue refers to a residue obtained by removing a hydroxyl group from a carboxyl group of HEPE.

[0187] Examples of HEPE include 15-hydroxyeicosapentaenoic acid (15-HEPE), 8-HEPE, 11-HEPE, and 18-HEPE.

[0188] The compound of general formula (I) (wherein R1 and R2 are combination A) is also called 1-(hydroxyeicosapentaenoyl)-sn-glycero-3-O-4'-(N,N,N-trimethyl)-homoserine or MGTS-1-HEPE.

[0189] The compound of general formula (I) (wherein R1 and R2 are combination B) is also called 2-(hydroxyeicosapentaenoyl)-sn-glycero-3-O-4'-(N,N,N-trimethyl)-homoserine or MGTS-2-HEPE.

[0190] The HETE residue refers to a residue obtained by removing a hydroxyl group from a carboxyl group of HETE.

[0191] Examples of HETE include 15-hydroxyeicosatetraenoic acid (15-HETE) and 11-HETE.

[0192] The compound of general formula (I) (wherein R1 and R2 are combination C) is also called 1-(hydroxyeicosatetraenoyl)-sn-glycero-3-O-4'-(N,N,N-trimethyl)-homoserine or MGTS-1-HETE.

[0193] The compound of general formula (I) (wherein R1 and R2 are combination D) is also called 2-(hydroxyeicosatetraenoyl)-sn-glycero-3-O-4'-(N,N,N-trimethyl)-homoserine or MGTS-2-HETE.

[0194] The EPA residue refers to a residue obtained by removing a hydroxyl group from a carboxyl group of EPA.

[0195] The compound of general formula (I) (wherein R1 and R2 are combination E) is also called 1-(eicosapentaenoyl)-sn-glycero-3-O-4'-(N,N,N-trimethyl)-homoserine or MGTS-1-EPA.

[0196] The compound of general formula (I) (wherein R1 and R2 are combination F) is also called 2-(eicosapentaenoyl)-sn-glycero-3-O-4'-(N,N,N-trimethyl)-homoserine or MGTS-2-EPA.

[0197] (2) Lysophosphatidylcholine (LPC) represented by general formula (II):

[0198] [Chemical formula 12]

[0199]

[0200] Wherein, R1 and R2 are any one of the following combinations A to D:

[0201] combination <![CDATA[R1]]> <![CDATA[R2]]> A HEPE residue hydrogen B hydrogen HEPE residue C Hydroxyperoxyeicosapentaenoic acid (HpEPE) residue hydrogen D hydrogen HpEPE residues

[0202] The HEPE residue refers to a residue obtained by removing a hydroxyl group from a carboxyl group of HEPE.

[0203] Examples of HEPE include 15-hydroxyeicosapentaenoic acid (15-HEPE), 8-HEPE, 11-HEPE, and 18-HEPE.

[0204] The compound of general formula (I) (wherein R1 and R2 are combination A) is also called 1-(hydroxyeicosapentaenoyl)-sn-glycero-3-phosphocholine or LPC-1-HEPE.

[0205] The compound of general formula (II) (wherein R1 and R2 are combination B) is also known as 2-(hydroxyeicosapentaenoyl)-sn-glycero-3-phosphocholine or LPC-2-HEPE.

[0206] The HpEPE residue refers to a residue obtained by removing a hydroxyl group from a carboxyl group of HpEPE.

[0207] Examples of HpEPE include 15-peroxyhydroxyeicosapentaenoic acid (15-HpEPE), 8-HpEPE, 11-HpEPE, and 18-HpEPE.

[0208] The compound of general formula (II) (wherein R1 and R2 are combination C) is also known as 1-(hydroperoxyeicosapentaenoyl)-sn-glycero-3-phosphocholine or LPC-1-HpEPE.

[0209] The compound of general formula (II) (wherein R1 and R2 are combination D) is also known as 2-(hydroperoxyeicosapentaenoyl)-sn-glycero-3-phosphocholine or LPC-2-HpEPE.

[0210] (3) 15-Hydroxyeicosapentaenoic acid (15-HEPE)

[0211] [Chemical formula 13]

[0212]

[0213] (4) 15-Hydroxyeicosatetraenoic acid (15-HETE)

[0214] [Chemical formula 14]

[0215]

[0216] (5) 15-Hydroxyeicosatrienoic acid (15-HETrE)

[0217] [Chemical formula 15]

[0218]

[0219] (6) 13-Hydroxyoctadecatrienoic acid (13-HOTrE)

[0220] [Chemical formula 16]

[0221]

[0222] (7) 13-Hydroxyoctadecadienoic acid (13-HODE)

[0223] [Chemical formula 17]

[0224]

[0225] In a preferred embodiment, the algae water extract may contain one or more compounds selected from the following Group A (Group A compounds), preferably two or more compounds, and more preferably four or more compounds.

[0226] 〔Group A〕

[0227] 15-HEPE;

[0228] A compound of formula (I) (wherein R1 and R2 are a combination of A or B);

[0229] A compound of formula (I) (wherein R1 and R2 are a combination of E or F); and

[0230] A compound of the general formula (II) (wherein R1 and R2 are a combination of A or B).

[0231] The algae water extract may contain one or more compounds selected from the following Group B, preferably three or more compounds, and more preferably six or more compounds.

[0232] [Group B]

[0233] 13-HOTrE;

[0234] 13-HODE;

[0235] 15-HETrE;

[0236] 15-HETE;

[0237] A compound of formula (I) (wherein R1 and R2 are combination C or D); and

[0238] A compound of the general formula (II) (wherein R1 and R2 are combination C or D).

[0239] [Method for producing algae water extract]

[0240] The method for producing the algae water extract is not particularly limited, but preferably includes the three steps of "culturing algae", "crushing algae" and "water extraction of the crushed algae", and more preferably also includes [chromatographic column purification of the water extract].

[0241] [Cultivation of algae]

[0242] Algae of the genus Nannochloropsis can be cultured according to known methods.

[0243] In addition to the ESM medium used in the examples described below, the NIES collection homepage ([online], [retrieved on September 21, 2022], Internet,<https: / / mcc.nies.go.jp / 02medium.html> ) in “2. Culture medium for marine and brackish water algae”, etc.

[0244] The culture conditions can be appropriately set according to the type of algae and the culture scale. Marine Nannochloropsis algae is preferably cultured at a temperature of 20 to 25°C and under white light or natural light (preferably with a light quantum density of 17 to 300 μmol / m 2 / sec) shaking culture or aeration culture.

[0245] 〔Crushing of algae〕

[0246] The effective ingredients are accumulated in the algae cells. In order to increase the yield of the effective ingredients, the present invention preferably crushes the algae cells before water extraction.

[0247] The pulverization step is not particularly limited as long as the algae cells can be destroyed. For example, algae cells recovered from the culture solution are suspended in a liquid medium and provided to a pulverization device to obtain algae pulverized material.

[0248] The liquid medium may be, for example, water, alcohol or a mixture of water and alcohol. In terms of safety during the amplification test, water (particularly pure water) is preferred. Alcohol may be, for example, methanol and ethanol, preferably methanol. The content of alcohol in the mixture of water and alcohol is 20% to 80% by mass, preferably 40% to 60% by mass, relative to the total mass of the mixture. 2-Morpholineethanesulfonic acid may also be added to the liquid medium for the purpose of adjusting pH.

[0249] Examples of the pulverizing device include a bead mill homogenizer, a pressure homogenizer, and an ultrasonic homogenizer.

[0250] [Water extraction of algae powder]

[0251] The step of water extraction is not particularly limited as long as the algae pulverized material and water are mixed. It is preferred to add water to the algae pulverized material, or the algae pulverized material may be added to water.

[0252] Prior to water extraction, the ground algae is preferably gelled with a gelling agent.

[0253] There is no particular limitation on the water used as the extraction solvent, and tap water, ion exchange water, pure water, ultrapure water, and distilled water can be used. In terms of the purity of the extract, pure water or ultrapure water is preferred. Pure water preferably has a conductivity of 1 μS / cm or less. Ultrapure water preferably has a conductivity of 0.0549 μS / cm or less and a TOC of 5 ppb or less. Pure water and ultrapure water can be manufactured using a commercially available manufacturing device (e.g., Milli-Q (registered trademark)).

[0254] The amount of water used is not particularly limited, and is used in a volume corresponding to 2 to 1000 times, preferably 5 to 100 times, and more preferably 10 to 80 times the wet mass (wet weight) of the algae to be pulverized.

[0255] The extraction is preferably performed by continuous extraction in which water (extraction solvent) is supplied while collecting the extract.

[0256] In terms of extraction speed, it is preferred to perform extraction while stirring.

[0257] The extraction temperature is not particularly limited, but is preferably 4 to 25° C. in order to suppress decomposition of the active ingredient.

[0258] The extraction time is not particularly limited, and is, for example, 0.5 to 36 hours.

[0259] 〔Chromatographic column purification of algae water extract〕

[0260] In order to improve the purity of the algae water extract, the water extract is preferably purified by chromatography.

[0261] Chromatographic column purification can use a chromatography column purification technique that utilizes hydrophobic interactions. For example, a solid phase chromatography column composed of a polymer (e.g., styrene / divinylbenzene polymer) into which a functional group (e.g., N-vinylpyrrolidone) effective for retaining polar compounds is introduced (e.g., trade name: STRATA-X; manufacturer: Shimadzu GLC), and a solid phase chromatography column filled with a synthetic adsorbent composed of a styrene polymer with a porous structure (trade name: SP850; manufacturer: Mitsubishi Chemical) can be appropriately used.

[0262] Chromatographic column purification can be performed multiple times.

[0263] 〔Weight Gain Inhibitor〕

[0264] One aspect of the present invention is a weight gain inhibitor containing a water extract of algae of the genus Nannochloropsis (hereinafter also referred to as "algae water extract") as an active ingredient.

[0265] The cause of weight gain is not particularly limited, and the present invention can be appropriately used for weight gain caused by intake of high-fat foods. Examples of high-fat foods include meals containing 20% ​​to 70% fat in terms of energy.

[0266] “Contains as an effective ingredient” means that the weight gain inhibitor contains the algae water extract in an amount sufficient to produce the desired inhibitory effect (ie, an effective amount).

[0267] The algae water extract may be a single species or a combination of multiple species.

[0268] The content of the algae water extract can be appropriately set in consideration of the dosage form (beverage, food, medicine, etc.). For example, in the case of a liquid food for human use, the content of the "Group A compound" as an active ingredient is preferably 0.001 to 8.35 mg / mL, and more preferably 0.005 to 3.34 mg / mL relative to the total volume of the liquid food.

[0269] The weight gain inhibitor may contain one or more optional components within the range not impairing the effect of the active ingredient. The optional components can be appropriately selected according to the dosage form and the like.

[0270] The optional ingredients may be additives for food, beverages or medicines.

[0271] Any component is a known substance and can be easily obtained on the market or can be prepared.

[0272] Any component may be used in a single species or in combination of multiple species.

[0273] The content of the optional components can be appropriately selected depending on the purpose of formulation and the like.

[0274] The weight gain inhibitor is not particularly limited and can be applied to a wide range of animal species. The applicable subjects are preferably mammals (humans and non-human mammals (such as cattle and horses)), and more preferably humans. In addition, the gender and age of the applicable subjects are not limited.

[0275] The intake amount of the weight gain inhibitor can be appropriately set according to the age and weight of the applicable subject, the route of administration, the number of administrations, etc. For example, in the case of oral administration to humans, the intake amount of the "Group A compound" is preferably 0.00162 to 0.815 mg / kg body weight / day, and more preferably 0.004 to 0.362 mg / kg body weight / day.

[0276] The intake interval can be appropriately set according to the intake amount, and may be once a day or divided into multiple intakes.

[0277] [Method for preparing weight gain inhibitor]

[0278] The weight gain inhibitor can be prepared by mixing the active ingredient (algae water extract) and an optional ingredient (for example, a food or beverage or a pharmaceutical additive).

[0279] [Usage form of weight gain inhibitor]

[0280] The weight gain inhibitor can be used as a beverage food or a medicine.

[0281] 〔Food and Beverage〕

[0282] The form of the food or drink is not particularly limited as long as it can be orally ingested. Specific examples include liquid drinks and jelly drinks.

[0283] Beverage foods include health foods, functional foods, nutritional supplements, foods for specific health purposes, foods for patients, beverage foods with disease risk reduction warnings, etc.

[0284] The food and drink may contain food additives as optional ingredients.

[0285] Examples of additives for liquid beverages include pH adjusters, emulsifiers, stabilizers, flavors, sweeteners, etc. Examples of additives for jelly drinks include gelatin, food coloring, and thickening polysaccharides.

[0286] 〔drug〕

[0287] The dosage form of the drug is preferably a dosage form that can be administered orally or intravenously, and specific examples include liquid preparations, capsules, and powders.

[0288] The drug may contain a drug additive as an optional component. Examples of the drug additive include excipients, stabilizers, preservatives, wetting agents, emulsifiers, lubricants, sweeteners, colorants, flavoring agents, buffers, antioxidants, pH adjusters, and the like.

[0289] [Blockers that promote cholesterol synthesis]

[0290] One aspect of the present invention is an inhibitor for promoting cholesterol synthesis, which contains a water extract of algae of the genus Nannochloropsis (hereinafter also referred to as "algae water extract") as an active ingredient.

[0291] The cause of promoting cholesterol synthesis is not particularly limited, and the present invention can be appropriately used for promoting cholesterol synthesis due to high-fat food intake. Examples of high-fat food include meals containing 20% ​​to 70% fat in energy ratio.

[0292] "Inhibition of cholesterol synthesis promotion" means inhibiting the expression of a gene involved in cholesterol synthesis promotion in the cholesterol synthesis system. Examples of such genes in humans include the following 11 types.

[0293] Gene name 3-Hydroxy-3-methylglutaryl-CoA synthase 1 3-Hydroxy-3-methylglutaryl CoA reductase Mevalonate (diphosphate) decarboxylase Farnesyl diphosphate farnesyltransferase 1 Squalene epoxidase Lanosterol synthase Cytochrome P450 family 51 subfamily A member 1 Methylsterol monooxygenase 1 NAD(P)-dependent steroid dehydrogenase-like Hydroxysteroid (17β) dehydrogenase 7 7-Dehydrocholesterol reductase

[0294] The algae water extract blocks the expression of one or more of the above 11 species, preferably blocks the expression of five or more species, and more preferably blocks the expression of all 11 species.

[0295] “Contains… as an effective ingredient” means that the cholesterol synthesis inhibitor contains an amount of the algae water extract sufficient to produce the desired inhibitory effect (ie, an effective amount).

[0296] The algae water extract may be a single species or a combination of multiple species.

[0297] The content of the algae water extract can be appropriately set in consideration of the dosage form (beverage, food, medicine, etc.). For example, in the case of a liquid food for human use, the content of the "Group A compound" as an active ingredient is preferably 0.001 to 8.35 mg / mL, and more preferably 0.005 to 3.34 mg / mL relative to the total volume of the liquid food.

[0298] The cholesterol synthesis inhibitor may contain one or more optional components within the range that does not impair the effect of the active ingredient. The optional components may be appropriately selected according to the dosage form and the like.

[0299] The optional ingredients may be additives for food or beverages or medicinal additives.

[0300] Any component is a known substance and can be easily obtained on the market or can be prepared.

[0301] Any component may be used in a single species or in combination of multiple species.

[0302] The content of the optional components can be appropriately selected depending on the purpose of formulation and the like.

[0303] There is no particular limitation on the cholesterol synthesis promoting inhibitor, and it can be applied to a wide range of animal species with a cholesterol synthesis system. The applicable subjects are preferably mammals (human beings and non-human mammals (e.g., cattle and horses)), and more preferably humans. In addition, the gender and age of the applicable subjects are not limited.

[0304] The intake amount of the cholesterol synthesis inhibitor can be appropriately set according to the age and weight of the applicable subject, the route of administration, the number of administrations, etc. For example, in the case of oral administration to humans, the intake amount of the "Group A compound" is preferably 0.00162 to 0.815 mg / kg body weight / day, and more preferably 0.004 to 0.362 mg / kg body weight / day.

[0305] The intake interval can be appropriately set according to the intake amount, and may be once a day or divided into multiple intakes.

[0306] [Preparation method of cholesterol synthesis inhibitor]

[0307] The cholesterol synthesis inhibitor can be prepared by mixing the effective ingredient (algae water extract) and an optional ingredient (for example, a food or beverage additive or a pharmaceutical additive).

[0308] [Usage form of inhibitors that promote cholesterol synthesis]

[0309] The weight gain inhibitor can be used as a beverage food or a medicine.

[0310] 〔Food and Beverage〕

[0311] The form of the food or drink is not particularly limited as long as it can be orally ingested. Specific examples include liquid drinks and jelly drinks.

[0312] Beverage foods include health foods, functional foods, nutritional supplements, foods for specific health purposes, foods for patients, beverage foods with disease risk reduction warnings, etc.

[0313] The food and drink may contain food additives as optional ingredients.

[0314] Examples of additives for liquid beverages include pH adjusters, emulsifiers, stabilizers, flavors, sweeteners, etc. Examples of additives for jelly drinks include gelatin, food coloring, and thickening polysaccharides.

[0315] 〔drug〕

[0316] Cholesterol synthesis inhibitors as drugs can be used to treat "diseases associated with cholesterol synthesis promotion". Examples of "diseases associated with cholesterol synthesis promotion" include non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), dyslipidemia and metabolic syndrome.

[0317] The dosage form of the drug is preferably a dosage form that can be administered orally or intravenously, and specific examples include liquid preparations, capsules, and powders.

[0318] The drug (drug composition) may contain a drug additive as an optional component. Examples of the drug additive include excipients, stabilizers, preservatives, wetting agents, emulsifiers, lubricants, sweeteners, colorants, flavors, buffers, antioxidants, pH adjusters, and the like.

[0319] [Example]

[0320] The present invention will be described in more detail below by way of examples, but the present invention is not limited to these examples.

[0321] [Cultivation of Nannochloropsis algae]

[0322] The Nannochloropsis oceanica NIES-2145 strain sold separately from the Microbial System Storage Facility of the National Institute for Environmental Studies of Japan was used.

[0323] As the culture medium, ESM medium having the following composition was used.

[0324] Element concentration <![CDATA[KNO3]]> 2.5g / L <![CDATA[Na2HPO4]]> 0.25g / L Vitamin B12 2.5 μg / L Biotin 2.5 μg / L Thiamine 0.5 μg / L Fe-EDTA 0.075g / L <![CDATA[ZnSO4·7H2O]]> 1.11mg / L <![CDATA[CuSO4·5H2O]]> 0.395mg / L <![CDATA[MoO3]]> 0.075mg / L <![CDATA[H3BO3]]> 14.3mg / L <![CDATA[MnCl2·4H2O]]> 9.05mg / L MARINE ART SF-1 38.3g / L water The total volume of the culture medium reaches 1L

[0325] 1 L of the pre-culture solution of NIES-2145 strain (cell number: 1×10 9 cells / mL) (number of cells in the culture medium after inoculation: 1×10 8 Air (CO2 concentration: 2%) was blown into the transparent container (flow rate: 3 L / min), and white light (light source: white LED; photon density: 300 μmol / m 2 / sec), and cultured at a liquid temperature of 20°C.

[0326] 〔Crushing of algae〕

[0327] On the third day of cultivation, about 70 g (wet mass) of algae was recovered by centrifugation. Pure water was added to the algae in an amount of 2 mL per 1 g of wet mass of the algae to suspend it. The total volume of the suspension was about 210 mL. 10 mL of the suspension and 25 g of zirconium oxide beads (particle size: 0.1 mm) were placed in a 50 mL grinding tube and ground with Multi-Beads Shocker (Yasui Instruments Co., Ltd., Japan) (2500 rpm for 1 minute) to obtain algae crushed material.

[0328] [Water extraction of algae powder]

[0329] The algae pulverized material is gelled using a gelling agent.

[0330] The gelled algae pulverized material was added to an extraction tank containing 71.4 volumes of pure water relative to the wet mass (wet weight) of the algae used for pulverization, and water extraction was performed at room temperature (about 25° C.) for 24 hours while stirring with a stirrer. During the water extraction, pure water (extraction solvent) was supplied to the extraction tank at a rate of 41 mL / min.

[0331] Citric acid was added to the effluent from the extraction tank until the concentration reached 0.0064% (w / v), and the resulting solution was further used for chromatography column purification.

[0332] 〔Chromatographic column purification of water extract〕

[0333] A chromatography column (3 cm inner diameter×22.5 cm height) filled with 150 mL of an adsorbent (trade name: SP850; manufacturer: Mitsubishi Chemical) was used.

[0334] The entire amount of the effluent from the extraction tank was loaded into the chromatography column, and then 450 mL of pure water was passed through the column for 15 minutes (the first washing of the adsorbent material).

[0335] The adsorbent material taken out from the chromatography column was transferred to a 1 L bottle containing 450 mL of pure water and stirred with a stirrer for 10 minutes to remove the solid matter mixed in the adsorbent material (second washing).

[0336] A 40% ethanol aqueous solution (450 mL) was added to the washed adsorbent, and the mixture was stirred for 10 minutes with a stirrer to remove foreign substances from the adsorbent (third washing).

[0337] The adsorbent material was again filled into a chromatography column (inner diameter 5 cm×height 50 cm), 450 mL of 100% ethanol was passed through, and the eluate was collected every 50 mL to separate 9 components (50 mL×9).

[0338] The 4th to 8th fractions were mixed in the order of elution and applied to an evaporator to obtain a brown solid.

[0339] 3 mL of ethanol was added to the solid to obtain an ethanol solution.

[0340] The ethanol solution was centrifuged to remove the ethanol insoluble components.

[0341] The supernatant obtained by centrifugation was cooled at -30°C for 30 minutes and centrifuged again to remove solid components.

[0342] The obtained supernatant was cooled again at -30°C for 30 minutes and used for centrifugal separation.

[0343] The obtained supernatant was used as a water extract of Nannochloropsis and was used for component analysis and animal testing described later.

[0344] 〔Analysis of components of Nannochloropsis algae water extract〕

[0345] Thin layer chromatography (TLC) and liquid chromatography-mass spectrometry (LC-MS) were used for component analysis.

[0346] The water extract of Nannochloropsis was spotted on a silica gel TLC plate and developed with two developing solvents: 100% methanol (mobile phase 1) and a mixed solvent of hexane, diethyl ether and acetic acid (volume ratio = 20:80:2) (mobile phase 2).

[0347] Three spots A to C visualized by TLC using mobile phase 1 and eight spots D to K visualized by TLC using mobile phase 2 were scraped off the TLC plate, respectively extracted again with 1 mL of ethanol, and used for LC-MS analysis under the following conditions.

[0348] HPLC conditions

[0349] Device Nexera-I LC-2040C 3D Chromatography columns KinetexTM C8(2.1mm ID×150mm L,2.6μm) Chromatography column oven 40℃ Solvent A 0.1% Formic acid-water Solvent B Acetonitrile flow 0.4mL Injection volume 10μL

[0350] MS conditions

[0351] Device LCMS-8050 Ionization method ESI positive / negative model MRM

[0352] The following compounds were identified from points B, C, E, and F.

[0353]

[0354] 〔Animal Testing〕

[0355] To evaluate the effects of aqueous extracts of Nannochloropsis spp. on (1) weight gain and (2) cholesterol synthesis in experimental animals fed a high-fat diet.

[0356] 〔Experimental Animals〕

[0357] C57 BL / 6N male mice (Charles River, Japan) introduced at 6 weeks of age were used after acclimation for 1 week.

[0358] 〔diet〕

[0359] A low-fat diet (LFD) (containing 10% of energy by fat) and a high-fat diet (HFD) (containing 45% of energy by fat) were used. Lard was used as fat, and the weight of fat content was adjusted using carbohydrates. The content of each nutrient excluding fat and carbohydrates was designed to be equivalent per unit of energy. Feed and drinking water were both ad libitum.

[0360] [Administration of test samples]

[0361] The dosing test samples containing the aqueous extract of Nannochloropsis were prepared according to the following steps.

[0362] The water extract of Nannochloropsis was diluted with ethanol to a 15-HEPE content of 0.2 mg / mL (for preparing low-dose samples) or 3.6 mg / mL (for preparing high-dose samples), and then injected into vials according to the daily usage amount and stored in a medical cryogenic box (-20°C) until the day of use.

[0363] The Nannochloropsis aqueous extract was transferred to the animal laboratory on ice (aluminum block) and allowed to stand at room temperature and protected from light, starting 30 minutes before sample preparation.

[0364] The water extract of Nannochloropsis algae was diluted 20 times with ultrapure water, mixed by inversion 10 times, and then allowed to stand for 15 minutes at room temperature and in the dark to obtain the following dosing test samples containing the water extract of Nannochloropsis algae at low and high doses. In addition, the ethanol concentration in each sample was 5% (v / v).

[0365] 15-HEPE content (mg / mL) Low dosage sample (HEPE low dosage; HL) 0.01 High Dosage Sample (HEPE High Dosage; HL) 0.18

[0366] 〔Animal Experiment Group〕

[0367] The evaluation was performed using the following 4 test groups.

[0368] Experimental group 1 (n=8) LFD uptake + solvent (5% (v / v) ethanol) administration (LFD) Experimental group 2 (n=9) HFD intake + solvent (5% (v / v) ethanol) administration (HFD) Experimental group 3 (n=8) HFD intake + low-dose medication (HFD+HL) Experimental group 4 (n=8) HFD intake + high dose medication (HFD+HH)

[0369] Test group 1 was set as a low-fat diet control group. A 5% (v / v) ethanol aqueous solution was administered, which was equivalent to the solvent used to prepare the test sample for administration.

[0370] Test group 2 was set as a high-fat diet control group. A 5% (v / v) ethanol aqueous solution was administered, which was equivalent to the solvent used to prepare the test sample for administration.

[0371] Experimental group 3 was set as a high-fat diet + low-dose administration group. The 15-HEPE administration dose in experimental group 3 was 0.1 mg / kg body weight / day.

[0372] Experimental group 4 was set as a high-fat diet + high-dose administration group. The 15-HEPE administration dose in experimental group 4 was 1.8 mg / kg body weight / day.

[0373] [Method of administration]

[0374] The administration of the test sample to the experimental animals was carried out through an oral intragastric catheter while the experimental animals were immobilized.

[0375] The low-dose sample and the high-dose sample were administered at 100 μL / 10 g of mouse body weight, respectively.

[0376] Each of the test groups 1 to 4 was administered once a day for 21 days, and the administration was carried out between 8 am and 12 pm every day.

[0377] 〔Management of experimental animals〕

[0378] The mice were reared in the following environment.

[0379] 〔Farming facilities〕

[0380] Temperature: within the range of 22±1.5℃

[0381] Humidity: within the range of 45% ± 5%

[0382] Light-dark cycle: Bright period 8:00-20:00; Dark period: 20:00-8:00

[0383] Solo feeding

[0384] [Example 1: Effect of suppressing weight gain]

[0385] The “weight gain from the base day” was calculated based on the body weight measurements on the first day of the experiment (base day) and the 22nd day of the experiment, which was the day following the last administration day. The distribution of the weight gain of each individual in each experimental group is shown in Figure 1 .

[0386] The body weight gain from the first day of the experiment (reference day) to the 22nd day of the experiment, which was the day following the final administration day, was evaluated using Steel's multiple comparison test. The results are shown in Tables 1-1 and 1-2.

[0387] [Table 1-1]

[0388]

[0389] [Table 1-2]

[0390]

[0391] At the significance level of 0.05, a significant difference was observed between test group 1 (LFD) and test group 2 (HFD) (p<0.05). This result indicates that high-fat diet (HFD) intake increases body weight compared to low-fat diet (LFD) intake.

[0392] A significant difference was observed between the experimental group 2 (HFD) and the experimental group 3 (HFD+HL) (p<0.05). This result indicates that the administration of a low dose of Nannochloropsis algae aqueous extract (HL) suppressed the weight gain caused by high-fat diet intake.

[0393] Although no significant difference was confirmed between test group 2 (HFD) and test group 4 (HFD+HH), it is believed that the weight gain caused by high-fat food intake can be suppressed by dividing the daily intake into several times (the intake amount of algae water extract each time is the same as that of HL) and administering a high dose of Nannochloropsis water extract (HL).

[0394] The “weight gain rate from the base day” was calculated based on the body weight measurements on the first day of the experiment (base day) and the 22nd day of the experiment, which was the day following the last administration day. The distribution of the weight gain rate of each individual in each test group is shown in Figure 2 .

[0395] The weight gain rate from the first day of the experiment (reference day) to the 22nd day of the experiment, which was the day following the final administration day, was evaluated using Steel's multiple comparison test. The results are shown in Tables 2-1 and 2-2.

[0396] [Table 2-1]

[0397]

[0398] [Table 2-2]

[0399]

[0400] At the significance level of 0.05, a significant difference was observed between test group 1 (LFD) and test group 2 (HFD) (p<0.05). This result indicates that high-fat diet (HFD) intake increases body weight compared to low-fat diet (LFD) intake.

[0401] A significant difference was observed between the experimental group 2 (HFD) and the experimental group 3 (HFD+HL) (p<0.05). This result indicates that the administration of a low dose of Nannochloropsis algae aqueous extract (HL) suppressed the weight gain caused by high-fat diet intake.

[0402] Although no significant difference was confirmed between test group 2 (HFD) and test group 4 (HFD+HH), it is believed that the weight gain caused by high-fat food intake can be suppressed by dividing the daily intake into several times (the intake amount of algae water extract each time is the same as that of HL) and administering a high dose of Nannochloropsis water extract (HL).

[0403] [Example 2: Blocking effect of promoting cholesterol synthesis]

[0404] Liver tissues collected from experimental animals on the 22nd day of the experiment, the day after the last administration, were used for transcriptome analysis using DNA microarrays (Thermo Fisher Scientific, Clariom S array, mouse). Expression changes of genes related to the cholesterol synthesis system between experimental groups were analyzed under the following conditions.

[0405] Combinations of between-group comparisons:

[0406] Experimental group 2 (HFD) versus experimental group 1 (LFD)

[0407] Experimental group 2 (HFD) versus experimental group 3 (HFD+HL)

[0408] Experimental group 2 (HFD) versus experimental group 4 (HFD+HH)

[0409] Computing environment: R version 4.0.3

[0410] Standardization: qFARMS (Information of FARMS: https: / / pubmed.ncbi.nlm.nih.gov / 16473874 / )

[0411] Comparative analysis between the two groups: Rank Products 2 (Information of Rank Products 2: https: / / pubmed.ncbi.nlm.nih.gov / 28481966 / )

[0412] Using the "false discovery rate (FDR)" as an indicator of significant expression changes, 11 genes that met the following "change condition 1" and "change condition 2-1 or 2-2" were judged to be "genes related to the promotion of cholesterol synthesis whose expression was increased by high-fat food intake (condition 1), but whose expression was reduced (blocked) by administration of Nannochloropsis algae water extract (condition 2)" (Table 3).

[0413] Change condition 1:

[0414] In the case of experimental group 2 (HFD) > experimental group 1 (LFD), FDR < 0.05

[0415] Change condition 2-1:

[0416] FDR<0.05 in trial group 2 (HFD) > trial group 3 (HFD+HL)

[0417] Change condition 2-2:

[0418] FDR<0.05 in experimental group 2 (HFD) > experimental group 4 (HFD+HH)

[0419] [Table 3]

[0420]

[0421]

[0422] INDUSTRIAL APPLICABILITY The present invention can be used in beverages, foods, medicines, and the like.

Claims

1. A weight gain inhibitor comprising a water extract of algae belonging to the genus Nannochloropsis as an active ingredient.

2. The inhibitor according to claim 1, wherein The water extract contains one or more compounds selected from the following [Group A]: 〔Group A〕 15-HEPE; Monoacylglycerol trimethyl homoserine represented by general formula (I); [Chemical formula 1] Wherein, R1 and R2 are the following combinations A, B, E or F: as well as Lysophosphatidylcholine represented by general formula (II), [Chemical formula 2] Wherein, R1 and R2 are the following combinations A or B:

3. The inhibitor according to claim 2, wherein The water extract also contains one or more compounds selected from the following [Group B]: [Group B] 13-HOTrE; 13-HODE; 15-HETrE; 15-HETE; Monoacylglycerol trimethyl homoserine represented by general formula (I); Wherein, R1 and R2 are the following combinations C or D: as well as Lysophosphatidylcholine represented by general formula (II), Where R1 and R2 are combination C or D:

4. The inhibitor according to claim 1, wherein The algae of the genus Nannochloropsis is Nannochloropsis oceanica. The inhibitor according to claim 1 , which inhibits weight gain caused by ingestion of a high-fat meal.

6. A food or drink for suppressing weight gain, comprising a water extract of algae belonging to the genus Nannochloropsis as an active ingredient.

7. The food and beverage according to claim 6, wherein: The water extract contains one or more compounds selected from the following [Group A]: 〔Group A〕 15-HEPE; Monoacylglycerol trimethyl homoserine represented by general formula (I); [Chemical formula 3] Wherein, R1 and R2 are the following combinations A, B, E or F: as well as Lysophosphatidylcholine represented by general formula (II), [Chemical formula 4] Wherein, R1 and R2 are the following combinations A or B:

8. The food and beverage according to claim 7, wherein: The water extract also contains one or more compounds selected from the following [Group B]: [Group B] 13-HOTrE; 13-HODE; 15-HETrE; 15-HETE; Monoacylglycerol trimethyl homoserine represented by general formula (I); Wherein, R1 and R2 are the following combinations C or D: as well as Lysophosphatidylcholine represented by general formula (II), Where R1 and R2 are combination C or D:

9. The food and beverage according to claim 6, wherein: The algae of the genus Nannochloropsis is Nannochloropsis oceanica. 10 . The food or drink according to claim 6 , which suppresses weight gain caused by ingestion of a high-fat meal.

11. An inhibitor for promoting cholesterol synthesis, comprising a water extract of algae belonging to the genus Nannochloropsis as an active ingredient.

12. The blocking agent according to claim 11, wherein The water extract contains one or more compounds selected from the following [Group A]: 〔Group A〕 15-HEPE; Monoacylglycerol trimethyl homoserine represented by general formula (I); [Chemical formula 5] Wherein, R1 and R2 are the following combinations A, B, E or F: as well as Lysophosphatidylcholine represented by general formula (II), [Chemical formula 6] Wherein, R1 and R2 are the following combinations A or B:

13. The blocking agent according to claim 12, wherein The water extract also contains one or more compounds selected from the following [Group B]: [Group B] 13-HOTrE; 13-HODE; 15-HETrE; 15-HETE; Monoacylglycerol trimethyl homoserine represented by general formula (I); Wherein, R1 and R2 are the following combinations C or D: as well as Lysophosphatidylcholine represented by general formula (II), Where R1 and R2 are combination C or D:

14. The blocking agent according to claim 11, wherein The algae of the genus Nannochloropsis is Nannochloropsis oceanica.

15. The blocking agent according to claim 11, which blocks the promotion of cholesterol synthesis caused by the intake of high-fat food.

16. A food or beverage for blocking cholesterol synthesis, comprising a water extract of algae belonging to the genus Nannochloropsis as an active ingredient.

17. The food and beverage according to claim 16, wherein: The water extract contains one or more compounds selected from the following [Group A]: 〔Group A〕 15-HEPE; Monoacylglycerol trimethyl homoserine represented by general formula (I); [Chemical formula 7] Wherein, R1 and R2 are the following combinations A, B, E or F: as well as Lysophosphatidylcholine represented by general formula (II), [Chemical formula 8] Wherein, R1 and R2 are the following combinations A or B:

18. The food and beverage according to claim 17, wherein: The water extract also contains one or more compounds selected from the following [Group B]: [Group B] 13-HOTrE; 13-HODE; 15-HETrE; 15-HETE; Monoacylglycerol trimethyl homoserine represented by general formula (I); Wherein, R1 and R2 are the following combinations C or D: as well as Lysophosphatidylcholine represented by general formula (II), Where R1 and R2 are combination C or D:

19. The food and beverage according to claim 16, wherein: The algae of the genus Nannochloropsis is Nannochloropsis oceanica. 20 . The food and beverage according to claim 16 , which blocks the promotion of cholesterol synthesis caused by ingestion of a high-fat meal.

21. A pharmaceutical composition for treating a disease associated with promotion of cholesterol synthesis, the pharmaceutical composition comprising a water extract of algae of the genus Nannochloropsis as an effective ingredient.

22. The pharmaceutical composition according to claim 21, wherein The water extract contains one or more compounds selected from the following [Group A]: 〔Group A〕 15-HEPE; Monoacylglycerol trimethyl homoserine represented by general formula (I); [Chemical formula 9] Wherein, R1 and R2 are the following combinations A, B, E or F: as well as Lysophosphatidylcholine represented by general formula (II), [Chemical formula 10] Wherein, R1 and R2 are the following combinations A or B:

23. The pharmaceutical composition according to claim 22, wherein The water extract also contains one or more compounds selected from the following [Group B]: [Group B] 13-HOTrE; 13-HODE; 15-HETrE; 15-HETE; Monoacylglycerol trimethyl homoserine represented by general formula (I); Wherein, R1 and R2 are the following combinations C or D: as well as Lysophosphatidylcholine represented by general formula (II), Where R1 and R2 are combination C or D:

24. The pharmaceutical composition according to claim 21, wherein The algae of the genus Nannochloropsis is Nannochloropsis oceanica.

25. The pharmaceutical composition according to claim 21, wherein The disease associated with promotion of cholesterol synthesis is selected from the group consisting of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), dyslipidemia and metabolic syndrome.

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