KR20160101786A - Composition for preventing or treating of obesity comprising FAM19A5 and screening method for agent for treatment of obesity using the same - Google Patents

Abstract

The present invention relates to a novel use of FAM19A5, and more specifically, to a composition for preventing or treating obesity, comprising FAM19A5 protein or an activator thereof; a screening method for an anti-obesity agent, comprising a step for treating with a selected compound, a biological sample collected from an organism in need of obesity prevention or treatment, and a step for detecting the FAM19A5 expression profile thereof; a composition for alleviating or treating anorexia, comprising FAM19A5 protein inhibitor; and a screening method for an orexigenic agent, comprising a step for treating with a selected compound, a biological sample collected from an organism in need of anorexia alleviation or treatment, and a step for detecting the FAM19A5 expression profile thereof. The increased expression level of FAM19A5 gene, and increased amount or activity of FAM19A5 protein has the effects of suppressing appetite and reducing body weight, and therefore, the composition of the present invention can be beneficially used as an anti-obesity agent. Also, controlling the expression level of FAM19A5 gene, or the amount or activity of FAM19A5 protein has the effects of stimulating appetite and increasing body weight, and therefore the composition of the present invention can be beneficially used as an orexigenic agent.

Description

TECHNICAL FIELD [0001] The present invention relates to a composition for preventing or treating obesity comprising a FAM19A5 protein, and a screening method for an obesity treating agent using the composition.

The present invention relates to a composition for preventing or treating obesity, and a method for screening a therapeutic agent for obesity using the same.

Food intake and its conversion into the body are an integral part of every living organism. Thus, deviations from ingestion and food conversion are problematic and can cause disease. Obesity occurs when excess calories are consumed in excess of the required calories and the excess calories accumulate excessively in the adipose tissue in the form of triglycerides.

Obesity can often lead to other diseases, such as diabetes, dyslipidemia, hypertension, arteriosclerosis and coronary heart disease. In addition, obesity increases the burden on support and moving organs, which can lead to chronic pain and disease, such as arthritis or osteoarthritis. Thus, obesity is a socially serious health problem.

Obesity, diet therapy, exercise therapy and behavior modification therapy in combination with the best treatment effect can be achieved, but for faster and better effect, obesity remedies or diet products are widely used.

Currently, anti-obesity products such as Xenical, Reductil and Exo-Rise have been developed. Xenical, the main ingredient of orlistat, is the world's first treatment for obesity. It inhibits the action of lipase to inhibit lipid absorption, reduce total cholesterol and LDL cholesterol, and improve blood sugar and blood pressure. see. Reductil, which is based on sibutramine, was approved by the FDA in 1997 and is sold in more than 30 countries. Its efficacy is to maintain sympathetic nervous system serotonin and noradrenaline at high concentrations to induce sympathetic nervous system depression and satiety. . Finally, exorizae is a non-prescription semi-finished product imported from France, which increases heat production to increase the body's basic metabolism, inhibit lipase activity, reduce intestinal fat absorption by 30%, increase noradrenaline production, . However, these drugs have side effects such as heart diseases, respiratory diseases, neurological diseases, etc., and their efficacy is low. Therefore, it is necessary to develop a more effective treatment for obesity.

However, the orlistat which is currently being used as a treatment for obesity has adverse effects such as fat spread, intestinal gas production, abdominal bloating, etc. Sibutramine is known to have side effects such as headache, dry mouth, anorexia, insomnia and constipation. Also, orlistat inhibits the absorption of vitamin E and vitamin D, while phentermine and sibutramine have side effects that increase heart rate, palpitations or dizziness.

1. Korean Patent No. 10-1068686.

In order to solve the above problems, it is an object of the present invention to provide a composition for preventing or treating obesity.

It is another object of the present invention to provide a screening method for treating obesity.

The present invention also provides a composition for improving or treating anorexia.

It is another object of the present invention to provide a screening method of an anorectic treatment agent.

In order to achieve the above object, the present invention provides a composition for preventing or treating obesity comprising a FAM19A5 protein or an activator thereof.

In accordance with another aspect of the present invention, there is provided a method for preventing or treating obesity comprising: treating a biological sample obtained from an individual in need thereof with a compound; And detecting the expression profile of FAM19A5. The present invention also provides a screening method for treating obesity.

According to another aspect of the present invention, there is provided a composition for improving or treating anorexia, comprising an inhibitor of FAM19A5 protein.

In accordance with another aspect of the present invention, there is provided a method for treating or reducing anorexia, comprising: treating a biological sample obtained from an individual in need of an improvement or treatment of an appetite loss, And detecting the expression profile of the FAM19A5. The present invention also provides a screening method for an anorectic treatment agent.

According to the present invention, the increased amount of the FAM19A5 gene and the increased amount or activity of the FAM19A5 protein inhibits the appetite and reduces body weight, so that it can be used not only as a therapeutic agent for obesity but also in a reduced amount of the FAM19A5 gene The reduced amount of FAM19A5 protein and activity of the FAM19A5 protein can be useful as an appetite stimulant since it promotes appetite and increases body weight.

FIG. 1 is a graph showing food intake and weight change by FAM19A5. FIG.

The treatment of obesity, which is a serious health problem in society, is performed in combination with diet therapy, exercise therapy, and obesity treatment for faster effect. However, currently developed drugs for obesity have side effects such as intestinal gas generation, headache, insomnia and constipation, as well as suppression of absorption of vitamin E and D and increase of heart rate.

Accordingly, the inventors of the present invention have confirmed that the control of FAM19A5 protein influences food intake and body weight change while studying a safer and more effective treatment for obesity, thereby completing the present invention.

The FAM19A5 (family with sequence similarity 19, member A5) is a member of the FAM19A family gene consisting of five highly homologous genes encoding small secreted proteins, contains conserved cysteine residues at fixed positions, CC - is associated with MIP-1 alpha, a member of the chemokine family gene. The protein is mainly expressed in the brain and spinal cord, and is known to act as a differentiation regulator that stimulates the production of astrocytes while being secreted by the nerve development process and adult neural stem cells.

The present invention provides a composition for preventing or treating obesity comprising the FAM19A5 protein or an activator thereof, wherein the composition can be provided as a pharmaceutical composition or a health food composition.

In addition, the invention provides a method of treating obesity comprising: treating any compound with a biological sample obtained from an individual in need of preventing or treating obesity; And detecting the expression profile of FAM19A5. The present invention also provides a screening method for treating obesity.

When the increase in the expression level of the FAM19A5 gene, the amount of the FAM19A5 protein, or the activity of the FAM19A5 protein is measured, the compound can be determined as an anti-obesity agent.

The biological sample may be a cell, a cell line containing the same, or a tissue containing the same, and may be a cell, but is not limited thereto.

The identification number of the FAM19A5 nucleotide (human) of the present invention is BC039396.1, and the identification number of the FAMA9A5 protein (human) is Q7Z5A7.

Chemotherapy is one of the most effective treatments for chemotherapy, but drug-induced loss of appetite occurs as a side effect. Due to weight loss and malnutrition, many patients suffer from cancer.

Recently, research on appetite stimulants for cancer patients has been actively conducted. Currently, many appetite stimulants such as Megger of Boryeong Pharm, APPLOROL suspension suspension of LG Life Sciences, and MESETRON suspension of DongSung Pharma have been developed.

According to the present invention, it has been confirmed that controlling the activity or expression of FAM19A5 has an effect on food intake and body weight gain.

Accordingly, the present invention provides a composition for improving or treating anorexia, comprising an inhibitor of FAM19A5 protein.

Such anorexia includes loss of appetite due to chemotherapy of cancer or tumor, and thus the composition of the present invention is characterized by being combined with known anti-cancer agents.

The known anticancer agents include paclitaxel, docetaxel, vincristine, vinblastine, vinorelbin, daunomycin, doxorubicin, topotecan, ), Irinotecan, actinomycin, and etopocid, but are not limited thereto.

The composition for improving or treating anorexia can be provided as a pharmaceutical composition or a health food composition.

In addition, the present invention provides a method for treating or preventing anorexia, comprising: treating any compound in a biological sample obtained from an individual in need thereof; And detecting the expression profile of the FAM19A5. The present invention also provides a screening method for an anorectic treatment agent.

When the decrease in the expression level of the FAM19A5 gene, the amount of the FAM19A5 protein, or the activity of the FAM19A5 protein is measured, the compound can be determined to be an anorectal treatment agent.

The biological sample may be a cell, a cell line containing the same, or a tissue containing the same, and may be a cell, but is not limited thereto.

The pharmaceutical composition comprising the FAM19A5 protein or an activator thereof or the pharmaceutical composition comprising the inhibitor of the FAM19A5 protein according to the present invention may be used as a carrier, an excipient, a disintegrant, a sweetener, a coating agent, a swelling agent, a lubricant, a lubricant, A buffer, a buffer, a bacteriostatic agent, a diluent, a dispersant, a surfactant, a binder and a lubricant.

Specific examples of carriers, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. Solid formulations for oral administration may be in the form of tablets, pills, powders, granules, capsules These solid preparations can be prepared by mixing at least one excipient, for example, starch, calcium carbonate, sucrose or lactose, gelatin, etc., into the composition. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, syrups and the like, and various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin which are commonly used simple diluents. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, suppositories, and the like. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. As the suppository base, witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like can be used.

The pharmaceutical composition according to the present invention may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterilized injection solutions according to a conventional method .

In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose, Lactose, gelatin, and the like.

In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included .

Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

The amount of the FAM19A5 protein, the activator thereof, or the inhibitor of the FAM19A5 protein, which is an active ingredient of the pharmaceutical composition according to the present invention, may vary depending on the age, sex, weight, and disease of the patient but is preferably 0.001 to 100 mg / kg, To 10 mg / kg may be administered once to several times per day.

Further, the dosage of the pharmaceutical composition comprising the FAM19A5 protein or its activator according to the present invention or the pharmaceutical composition comprising the inhibitor of the FAM19A5 protein may be increased or decreased depending on the route of administration, degree of disease, sex, weight, age, . Thus, the dosage amounts are not intended to limit the scope of the invention in any manner.

The pharmaceutical composition may be administered to mammals such as rats, mice, livestock, humans, and the like in a variety of routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intratracheal, intrauterine or intracerebroventricular injections.

The health food composition comprising the FAM19A5 protein according to the present invention or an activator thereof or the health food composition comprising the inhibitor of FAM19A5 protein may be provided in the form of a powder, a granule, a tablet, a capsule, a syrup or a drink, The food is used with food or food additives other than the active ingredient FAM19A5 protein, an activator thereof or an inhibitor of the FAM19A5 protein, and can be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to its use purpose, for example, prevention, health or therapeutic treatment.

The effective dose of the FAM19A5 protein, its activator or the inhibitor of the FAM19A5 protein contained in the health food composition may be used according to the effective dose of the pharmaceutical composition, but may be used for health and hygiene purposes or for a long term The amount of the active ingredient may be less than the above range, and since the active ingredient has no problem in terms of safety, it can be used in an amount exceeding the above range.

There is no particular limitation on the type of the health food, and examples thereof include meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, Drinks, alcoholic beverages and vitamin complexes.

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail with reference to the following examples. However, the following examples are intended to illustrate the contents of the present invention, but the scope of the present invention is not limited to the following examples. Embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art.

< Example  1> Cerebral blood vessel  of mine Cannulae  for Orthopedic surgery ( Stereotaxic  surgery)

Animals were anesthetized by IP injection of tribromoethanol (250 mg / kg, Sigma-Aldrich, St. Louis, Mo., USA) and injected into a stereotaxic apparatus (Stoelting, Wood Dale, IL, USA). Were injected into the right ventricle of the cannula (26 gauge) (1.0 mm lateral, 0.3 mm posterior and 2.4 mm ventral to bregam) and secured to the skull with dental cement.

For the mouse, a polyethylene cannula (o.d 1.05 mm, i.d 0.35 mm) was injected into the ventricle (1.6 mm (width), 1.0 mm (posterior), top (3.6 mm) abdomen).

After the animals recovered from the anesthesia, they maintained a warm temperature and placed them in individual cages. After the operation, the patient was allowed to recover for about 7 days before the experiment, and the test material was injected through the cannula.

< Example  2> Of FAM19A5 ICV (Injection in the ventricle, intracerebroventricularly  injection) management

FAM19A5 was dissolved in sterile physiological saline and injected intravenously (icv, 1 μg / mice).

< Example  3> Food Intake and Weight  Change measurement

After the administration of FAM19A5, changes in food intake and body weight were measured directly on an hourly basis. At this time, 0.9% saline was supplied to the control group. Data are represented as mean ± SEM (CTL n = 4, FAM19A5 n = 3) (* p <0.05 vs. control mouse).

As a result, as shown in Fig. 1, it was confirmed that the food intake and body weight were significantly lowered in the group to which FAM19A5 was administered.

< Example  4> Immunochemical staining

The mice were anesthetized with triboromoethanol (250 mg / kg, Sigma-Aldrich, St. Louis, Mo., USA) and transcardially transfected with phosphate buffer (PB, 0.1M, pH 7.4) Fresh perfusion solution 4% paraformaldehyde was perfused, and heparin (10 mg / L) contained in cold 0.9% saline was perfused.

The brain was incised and fixed with the fixative overnight. The cells were then washed several times in cold PB (0.1 M) and digested with the hypothalamic ARC (arcuate hypothalamic nuclei) using a vibratome (VT1000P; Leica Microsystems, Wetzlar, Germany).

Coronal brain sections of 50 μm thickness were washed several times with PB and placed in PB containing 1% hydrogen peroxide (H ₂ O ₂ ) to block the activity of endogenous peroxidase and incubated for 20 min in the dark Respectively.

PB, and then pre-incubated for 30 minutes in PB containing 0.2% Triton X-100.

After washing with PB, sections and primary antibody were added to the shaker and allowed to react for 15 hours at 4 ° C.

After washing with PB, the section and secondary antibody were added to the shaker and reacted at room temperature for 2 hours.

Claims (8)

A composition for preventing or treating obesity comprising FAM19A5 protein or an activating agent thereof. The method according to claim 1,
Wherein the composition is selected from a pharmaceutical composition or a health food composition. Treating any compound with a biological sample obtained from an individual in need of preventing or treating obesity; And detecting the expression profile of said FAM19A5. A composition for improving or treating anorexia, comprising an inhibitor of FAM19A5 protein. 5. The method of claim 4,
Wherein said loss of appetite comprises loss of appetite due to cancer or tumor chemotherapy. 5. The method of claim 4,
A composition for improving or treating anorexia, wherein the composition is used in combination with a known anticancer agent. 5. The method of claim 4,
Wherein the composition is selected from a pharmaceutical composition or a health food composition. Treating any compound in a biological sample obtained from an individual in need of ameliorating or treating anorexia; And detecting the expression profile of said FAM19A5.

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