Method of obtaining factor associated with control of food consumption and/or body weight, polypeptide, possessing activity of food consumption suppression and/or weight gain, polipeptide-coding nucleic acid molecule, methods and polypeptide application

FIELD: medicine.

SUBSTANCE: elaborated is method of obtaining factor, which takes part in process of control of appetite and/or body weight. Also described are genes, obtained by said method, polypeptides, coded by said genes, intended for treatment, control or diagnostics of diseases, associated with eating disorders and/or control of body weight. Invention also relates to substances, which inhibit activity of said genes or said polypeptides, intended for treatment, control or diagnostics of diseases, associated with process of appetite and/or body weight control.

EFFECT: using tiasolidindions, possessing PPARγ-agonistic activity, it is possible to obtain genes and polypeptides, involved into regulation of appetite and/or body weight reduction.

27 cl, 41 dwg, 35 ex

 

The text descriptions are given in facsimile form.

1. A method of obtaining a factor that is associated with the control of food intake and/or body weight, containing the following steps:
the impact of the connection thiazolidinedione with PPARγ-agonistic activity, in a cell of a mammal, and
getting genes, the expression of which is induced by the specified connection, and the selection and identification of the gene encoding the protein containing the signal peptide of the above obtained genes.

2. The polypeptide consisting of the amino acid sequence shown in any of SEQ ID nos: 13-15, 39-41, 65-73, 101-103 or 107-115 having activity of suppressing food intake and/or suppressing gaining weight.

3. The polypeptide according to claim 2, in which the amino acid sequence shown in any of SEQ ID nos: 13-15.

4. The polypeptide according to claim 3, in which at least one amino acid residue is chemically modified compound or peptide.

5. Polypeptide having an activity of suppressing food intake and/or suppressing gaining weight that contain amino acid sequence having a homology of at least 80% with the amino acid sequence shown in any of SEQ ID nos: 13-15, 39-41, 65-73, 101-103 and 107-115.

6. The polypeptide according to claim 5, which consists of an amino acid sequence having a homology of at least 80% amino acid sequence shown is in any of SEQ ID nos: 13-15.

7. The polypeptide according to claim 5, where the activity of suppressing the gain in weight is the active suppression of adding body fat.

8. The polypeptide according to claim 6, in which at least one amino acid residue is chemically modified compound or peptide.

9. A fragment of a polypeptide according to claim 5, having an activity of suppressing food intake and/or suppressing gaining weight that contain amino acid sequence found in any of SEQ ID nos: 39-41, 65-73, 101-103 or 107-115.

10. A fragment of a polypeptide according to claim 9, in which at least one amino acid residue is chemically modified compound or peptide.

11. The nucleic acid molecule encoding a polypeptide listed in any one of claim 2, 5 and 7, where the polypeptide has an activity of suppressing food intake and/or suppressing gaining weight.

12. The nucleic acid molecule consisting of the nucleotide sequence shown in any of SEQ ID nos: 18-20, 44-46, 74-82, 104-106 or 116-124 encoding a polypeptide having an activity of suppressing food intake and/or suppressing gaining weight.

13. The molecule of nucleic acid, which hybridizes with the nucleotide sequence shown in any of SEQ ID nos: 18-20, 44-46, 74-82, 104-106, or 116-124, or its partial sequence under very stringent conditions, and which encodes the floor of the peptide, having activity of suppressing food intake and/or suppressing gaining weight.

14. The nucleic acid molecule according to any one of § § 11-13 where a specified activity suppression gaining weight is an activity of suppressing adding body fat.

15. The expression vector containing the nucleic acid molecule according to any one of § § 11-14.

16. The transformant containing the nucleic acid molecule according to any one of § § 11-14 expressing a polypeptide having an activity of suppressing food intake and/or suppressing gaining weight.

17. The pharmaceutical composition for suppressing food intake and/or suppressing gaining weight, containing polypeptide according to any one of claim 2, 5 and 7 or its fragment that retains all the properties of the polypeptide according to any one of claim 2, 5 and 7, the vector according to item 15 or the transformant according to item 16, as an active ingredient.

18. The pharmaceutical composition according to 17, in which the activity of suppressing the gain in weight is the active suppression of adding body fat.

19. The antibody against the polypeptide according to any one of claim 2, 5 and 7.

20. The method of producing the polypeptide according to any one of claim 2, 5, and 7, comprising the following stages (a) or (b):
(a) the cultivation of transformant in article 16, and removing the produced polypeptide from transformant; or
(b) implementation of the method, the peptide is Intesa.

21. Analytical method for predicting or diagnosing the condition of increased food intake or increased gaining weight, containing stage:
detection is contained in the number of molecules of nucleic acid containing the nucleotide sequence specified in any of SEQ ID nos: 10-12, 18-20, 44-46, 74-82, 104-106 and 116-124, or polypeptide containing the amino acid sequence found in any of SEQ ID NO: 3, 6, 9, 13-15, 39-41, 65-73, 101-103 and 107-115, in a biological sample from the mammal; and
prediction or diagnosis that the mammal is in a state of heightened food intake or increased gaining weight, detected when a specified number is lower compared to the quantity contained in a biological sample obtained from a normal individual.

22. A set of reagents for use in the analytical method according to item 21, containing:
at least one of: primer for PCR, probe or a DNA chip for detection of a nucleic acid molecule containing the nucleotide sequence specified in any of SEQ ID nos: 10-12, 18-20, 44-46, 74-82, 104-106 and 116-124; or an antibody that recognizes the polypeptide containing the amino acid sequence found in any of SEQ ID NO: 3, 6, 9, 13-15, 39-41, 65-73, 101-103 or 107-115, standard peptide or modified peptide for competitive Rea is the binding.

23. Method of screening a therapeutic or preventive agent having an overwhelming effect on food intake and/or gaining weight, contains the following stages:
the bringing into contact of the analyte with the cell of the mammal, and detecting increased expression of a gene in a given cell containing the nucleotide sequence specified in any of SEQ ID nos: 10-12, 18-20, 44-46, 74-82, 104-106 and 116-124, or the increased amount of the polypeptide contained intracellular specified in the cell or secreted extracellular containing the amino acid sequence found in any of SEQ ID NO: 3, 6, 9, 13-15, 39-41, 65-73, 101-103 and 107-115.

24. Method of screening a therapeutic or preventive agent having an overwhelming effect on food intake and/or gaining weight, contains the following stages:
the introduction of the analyte to the mammal and
the detection of increased expression of the gene containing the nucleotide sequence specified in any of SEQ ID nos: 10-12, 18-20, 44-46, 74-82, 104-106 or 116-124, or increased production of the polypeptide containing the amino acid sequence found in any of SEQ ID NO: 3, 6, 9, 13-15, 39-41, 65-73, 101-103 or 107-115, in a biological sample from the specified investigational animal.

25. Method of screening a therapeutic or prophylactic the ski agent, with overwhelming effect in relation to food intake and/or gaining weight, contains the following stages:
the introduction of the analyte knocked out an animal, not a person, in which the whole area or part of the gene containing the nucleotide sequence specified in any of SEQ ID nos: 10-12, 18-20, 44-46, 74-82, 104-106 and 116-124, was removed, and the detection suppression of food intake or gaining weight at a specified animal, not a person.

26. Therapeutic or prophylactic agent that has an overwhelming effect on food intake and/or gaining weight, obtained in accordance with the method according to any of p-25.

27. The pharmaceutical composition for suppressing food intake and/or suppressing gaining weight, containing:
the polypeptide containing the amino acid sequence found in any of SEQ ID NO: 3, 6, 9, 13-15, 39-41, 65-73, 101-103 and 107-115, or its fragment that retains all the properties of the polypeptide according to any one of claim 2, 5 and 7; or
the vector or the transformant containing a nucleic acid molecule containing the nucleotide sequence specified in any of SEQ ID nos: 10-12, 18-20, 44-46, 65-73, 74-82, 104-106 or 116-124 as the active ingredient.



 

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