Pharmaceutical composition, food or drink, and methods related thereto

Abstract

A pharmaceutical composition including, as an active ingredient, one of the following proteins (I) and (II): (I) an apoptosis inhibitor of macrophage; and (II) a protein which consists of an amino acid sequence having deletion, substitution, or addition of one or more amino acids in an amino acid sequence of the apoptosis inhibitor of macrophage and having homology to the amino acid sequence of the apoptosis inhibitor of macrophage, and has a function of inhibiting the differentiation of preadipocytes to mature adipocytes and/or a function of inducing lipolysis in the mature adipocytes.

1 . A pharmaceutical composition comprising, as an active ingredient, one of the following proteins (I) and (II):
 (I) an apoptosis inhibitor of macrophage; and   (II) a protein which consists of an amino acid sequence having deletion, substitution, or addition of one or more amino acids in an amino acid sequence of the apoptosis inhibitor of macrophage and having homology to the amino acid sequence of the apoptosis inhibitor of macrophage, and has a function of inhibiting differentiation of preadipocytes to mature adipocytes and/or a function of inducing lipolysis in the mature adipocytes.   
     
     
         2 . A pharmaceutical composition according to  claim 1 , comprising the protein (I) as the active ingredient. 
     
     
         3 . A pharmaceutical composition according to  claim 2 , wherein the protein (I) is a protein which consists of an amino acid sequence shown in Sequence Listing 1. 
     
     
         4 . A pharmaceutical composition according to  claim 2 , wherein the protein (I) is an apoptosis inhibitor of macrophage of an animal. 
     
     
         5 . A pharmaceutical composition according to  claim 4 , wherein the animal is one of a mouse, a dog, and a cat. 
     
     
         6 . A pharmaceutical composition according to  claim 1 , comprising the protein (II) as the active ingredient. 
     
     
         7 . A pharmaceutical composition according to  claim 6 , wherein the protein (II) is a protein which consists of an amino acid sequence having deletion, substitution, or addition of one or more amino acids in an amino acid sequence shown in Sequence Listing 1 and having 80% or more homology to the amino acid sequence shown in Sequence Listing 1, and has a function of inhibiting differentiation of preadipocytes to mature adipocytes and/or a function of inducing lipolysis in the mature adipocytes. 
     
     
         8 . A pharmaceutical composition according to  claim 7 , wherein the protein (II) is a protein which consists of an amino acid sequence having deletion, substitution, or addition of one or several amino acids in an amino acid sequence shown in Sequence Listing 1, and has a function of inhibiting differentiation of preadipocytes to mature adipocytes and/or a function of inducing lipolysis in the mature adipocytes. 
     
     
         9 . A pharmaceutical composition according to  claim 6 , wherein the protein (II) is a protein which consists of an amino acid sequence having deletion, substitution, or addition of one or more amino acids in an amino acid sequence shown in Sequence Listing 1, is formed by tandemly linking a first domain consisting of one of an amino acid sequence shown in Sequence Listing 2 and an amino acid sequence having deletion, substitution, or addition of one or more amino acids in the amino acid sequence shown in Sequence Listing 2 and having 80% or more homology to the amino acid sequence shown in Sequence Listing 2, a second domain consisting of one of an amino acid sequence shown in Sequence Listing 3 and an amino acid sequence having deletion, substitution, or addition of one or more amino acids in the amino acid sequence shown in Sequence Listing 3 and having 80% or more homology to the amino acid sequence shown in Sequence Listing 3, and a third domain consisting of one of an amino acid sequence shown in Sequence Listing 4 and an amino acid sequence having deletion, substitution, or addition of one or more amino acids in the amino acid sequence shown in Sequence Listing 4 and having 80% or more homology to the amino acid sequence shown in Sequence Listing 4, and has a function of inhibiting differentiation of preadipocytes to mature adipocytes and/or a function of inducing lipolysis in the mature adipocytes. 
     
     
         10 . A pharmaceutical composition according to  claim 9 , wherein the protein (II) is a protein which is formed by tandemly linking a first domain consisting of one of an amino acid sequence shown in Sequence Listing 2 and an amino acid sequence having deletion, substitution, or addition of one or several amino acids in the amino acid sequence shown in Sequence Listing 2, a second domain consisting of one of an amino acid sequence shown in Sequence Listing 3 and an amino acid sequence having deletion, substitution, or addition of one or several amino acids in the amino acid sequence shown in Sequence Listing 3, and a third domain consisting of one of an amino acid sequence shown in Sequence Listing 4 and an amino acid sequence having deletion, substitution, or addition of one or several amino acids in the amino acid sequence shown in Sequence Listing 4, and has a function of inhibiting differentiation of preadipocytes to mature adipocytes and/or a function of inducing lipolysis in the mature adipocytes. 
     
     
         11 . A pharmaceutical composition according to  claim 10 , wherein, the protein (II) is a protein which is formed by tandemly linking a first domain consisting of an amino acid sequence shown in Sequence Listing 2, a second domain consisting of an amino acid sequence shown in Sequence Listing 3, and a third domain consisting of an amino acid sequence shown in Sequence Listing 4, and has a function of inhibiting differentiation of preadipocytes to mature adipocytes and/or function of inducing lipolysis in the mature adipocytes. 
     
     
         12 . A pharmaceutical composition according to  claim 9 , wherein the protein (II) is a protein which is formed by tandemly and directly linking the first domain, the second domain, and the third domain, and has a function of inhibiting differentiation of preadipocytes to mature adipocytes and/or function of inducing lipolysis in the mature adipocytes. 
     
     
         13 . A pharmaceutical composition according to  claim 6 , wherein the protein (II) is a protein which is formed by tandemly linking a first domain consisting of one of an amino acid sequence shown in Sequence Listing 2 and an amino acid sequence having deletion, substitution, or addition of one or more amino acids in a portion other than a consensus sequence in the amino acid sequence shown in Sequence Listing 2, a second domain consisting of one of an amino acid sequence shown in Sequence Listing 3 and an amino acid sequence having deletion, substitution, or addition of one or more amino acids in a portion other than a consensus sequence in the amino acid sequence shown in Sequence Listing 3, and a third domain consisting of one of an amino acid sequence shown in Sequence Listing 4 and an amino acid sequence having deletion, substitution, or addition of one or more amino acids in a portion other than a consensus sequence in the amino acid sequence shown in Sequence Listing 4, and has a function of inhibiting differentiation of preadipocytes to mature adipocytes and/or a function of inducing lipolysis in the mature adipocytes. 
     
     
         14 . A pharmaceutical composition according to  claim 13 , wherein the protein (II) is a protein which is formed by tandemly and directly linking the first domain, the second domain, and the third domain, and has a function of inhibiting differentiation of preadipocytes to mature adipocytes and/or a function of inducing lipolysis in the mature adipocytes. 
     
     
         15 . A pharmaceutical composition according to  claim 6 , wherein the protein (II) is one of the following proteins (x1), (x2), and (x3), which has a function of inhibiting differentiation of preadipocytes to mature adipocytes and/or a function of inducing lipolysis in the mature adipocytes:
 (x1) one of a first domain protein consisting of an amino acid sequence shown in Sequence Listing 2 and a protein formed by tandemly linking a plurality of the first domain proteins;   (x2) one of a second domain protein consisting of an amino acid sequence shown in Sequence Listing 3 and a protein formed by tandemly linking a plurality of the second domain proteins; and   (x3) one of a third domain protein consisting of an amino acid sequence shown in Sequence Listing 4 and a protein formed by tandemly linking a plurality of the third domain proteins.   
     
     
         16 . A pharmaceutical composition according to  claim 6 , wherein the protein (II) is a protein which consists of an amino acid sequence having deletion, substitution, or addition of one or more amino acids in an amino acid sequence of an apoptosis inhibitor of macrophage of an animal and having 80% or more homology to the amino acid sequence of the apoptosis inhibitor of macrophage of the animal, and has a function of inhibiting differentiation of preadipocytes to mature adipocytes and/or a function of inducing lipolysis in the mature adipocytes. 
     
     
         17 . A pharmaceutical composition according to  claim 16 , wherein the animal is one of a mouse, a dog, and a cat. 
     
     
         18 . A pharmaceutical composition according to  claim 16 , wherein the protein (II) is a protein which consists of an amino acid sequence having deletion, substitution, or addition of one or several amino acids in an amino acid sequence of an apoptosis inhibitor of macrophage of an animal, and has a function of inhibiting differentiation of preadipocytes to mature adipocytes and/or a function of inducing lipolysis in the mature adipocytes. 
     
     
         19 . A pharmaceutical composition according to  claim 18 , wherein the animal is one of a mouse, a dog, and a cat. 
     
     
         20 . A pharmaceutical composition according to  claim 6 , wherein the protein (II) is a protein which consists of an amino acid sequence having deletion, substitution, or addition of one or more amino acids in an amino acid sequence of an apoptosis inhibitor of macrophage having an SRCR1 domain, an SRCR2 domain, and an SRCR3 domain of an animal, is formed by tandemly linking a first domain consisting of one of an amino acid sequence of the SRCR1 domain and an amino acid sequence having deletion, substitution, or addition of one or more amino acids in the amino acid sequence of the SRCR1 domain and having 80% or more homology to the amino acid sequence of the SRCR1 domain, a second domain consisting of one of an amino acid sequence of the SRCR2 domain and an amino acid sequence having deletion, substitution, or addition of one or more amino acids in the amino acid sequence of the SRCR2 domain and having 80% or more homology to the amino acid sequence of the SRCR2 domain, and a third domain consisting of one of an amino acid sequence of the SRCR3 domain and an amino acid sequence having deletion, substitution, or addition of one or more amino acids in the amino acid sequence of the SRCR3 domain and having 80% or more homology to the amino acid sequence of the SRCR3 domain, and has a function of inhibiting differentiation of preadipocytes to mature adipocytes and/or a function of inducing lipolysis in the mature adipocytes. 
     
     
         21 . A pharmaceutical composition according to  claim 20 , wherein the animal is one of a mouse, a dog, and a cat. 
     
     
         22 . A pharmaceutical composition according to  claim 20 , wherein the protein (II) is a protein which is formed by tandemly linking a first domain consisting of one of an amino acid sequence of the SRCR1 domain and an amino acid sequence having deletion, substitution, or addition of one or several amino acids in the amino acid sequence of the SRCR1 domain, a second domain consisting of one of an amino acid sequence of the SRCR2 domain and an amino acid sequence having deletion, substitution, or addition of one or several amino acids in the amino acid sequence of the SRCR2 domain, and a third domain consisting of one of an amino acid sequence of the SRCR3 domain and an amino acid sequence having deletion, substitution, or addition of one or several amino acids in the amino acid sequence of the SRCR3 domain, and has a function of inhibiting differentiation of preadipocytes to mature adipocytes and/or a function of inducing lipolysis in the mature adipocytes. 
     
     
         23 . A pharmaceutical composition according to  claim 22 , wherein the animal is one of a mouse, a dog, and a cat. 
     
     
         24 . A pharmaceutical composition according to  claim 20 , wherein the protein (II) is a protein which is formed by tandemly linking a first domain consisting of an amino acid sequence of the SRCR1 domain, a second domain consisting of an amino acid sequence of the SRCR2 domain, and a third domain consisting of an amino acid sequence of the SRCR3 domain, and has a function of inhibiting differentiation of preadipocytes to mature adipocytes and/or a function of inducing lipolysis in the mature adipocytes. 
     
     
         25 . A pharmaceutical composition according to  claim 24 , wherein the animal is one of a mouse, a dog, and a cat. 
     
     
         26 . A pharmaceutical composition according to  claim 20 , wherein the protein (II) is a protein which is formed by tandemly and directly linking the first domain, the second domain, and the third domain, and has a function of inhibiting differentiation of preadipocytes to mature adipocytes and/or a function of inducing lipolysis in the mature adipocytes. 
     
     
         27 . A pharmaceutical composition according to  claim 6 , wherein the protein (II) is a protein which consists of an amino acid sequence having deletion, substitution, or addition of one or more amino acids in an amino acid sequence of an apoptosis inhibitor of macrophage having an SRCR1 domain, an SRCR2 domain, and an SRCR3 domain of an animal, is formed by tandemly linking a first domain consisting of one of an amino acid sequence of the SRCR1 domain and an amino acid sequence having deletion, substitution, or addition of one or more amino acids in a portion other than a consensus sequence in the amino acid sequence of the SRCR1 domain, a second domain consisting of one of an amino acid sequence of the SRCR2 domain and an amino acid sequence having deletion, substitution, or addition of one or more amino acids in a portion other than a consensus sequence in the amino acid sequence of the SRCR2 domain, and a third domain consisting of one of an amino acid sequence of the SRCR3 domain and an amino acid sequence having deletion, substitution, or addition of one or more amino acids in a portion other than a consensus sequence in the amino acid sequence of the SRCR3 domain, and has a function of inhibiting differentiation of preadipocytes to mature adipocytes and/or a function of inducing lipolysis in the mature adipocytes. 
     
     
         28 . A pharmaceutical composition according to  claim 27 , wherein the animal is one of a mouse, a dog, and a cat. 
     
     
         29 . A pharmaceutical composition according to  claim 27 , wherein the protein (II) is a protein which is formed by tandemly and directly linking the first domain, the second domain, and the third domain, and has a function of inhibiting differentiation of preadipocytes to mature adipocytes and/or a function of inducing lipolysis in the mature adipocytes. 
     
     
         30 . A pharmaceutical composition according to  claim 6 , wherein the protein (II) is one of the following proteins (p1), (p2), and (p3), which has a function of inhibiting differentiation of preadipocytes to mature adipocytes and/or a function of inducing lipolysis in the mature adipocytes:
 (p1) one of a first domain protein consisting of an amino acid sequence of an SRCR1 domain in an apoptosis inhibitor of macrophage of an animal and a protein formed by tandemly linking a plurality of the first domain proteins;   (p2) one of a second domain protein consisting of an amino acid sequence of an SRCR2 domain in the apoptosis inhibitor of macrophage of the animal and a protein formed by tandemly linking a plurality of the second domain proteins; and   (p3) one of a third domain protein consisting of an amino acid sequence of an SRCR3 domain in the apoptosis inhibitor of macrophage of the animal and a protein formed by tandemly linking a plurality of the third domain proteins.   
     
     
         31 . A pharmaceutical composition according to  claim 30 , wherein the animal is one of a mouse, a dog, and a cat. 
     
     
         32 . A pharmaceutical composition according to  claim 1 , wherein the pharmaceutical composition is administered to a human. 
     
     
         33 . A pharmaceutical composition according to  claim 1 , wherein the pharmaceutical composition is administered to an animal. 
     
     
         34 . A pharmaceutical composition according to  claim 33 , wherein the animal is one of a mouse, a dog, and a cat. 
     
     
         35 . A protein which is the protein (I) or the protein (II) according to  claim 1 , wherein the protein is used as an active ingredient of a pharmaceutical composition. 
     
     
         36 . A method comprising producing the pharmaceutical composition according to  claim 1 . 
     
     
         37 . A method comprising administering the pharmaceutical composition according to  claim 1  to a living body. 
     
     
         38 . A method according to  claim 37 , wherein the living body is a human. 
     
     
         39 . A method according to  claim 37 , wherein the living body is an animal. 
     
     
         40 . A pharmaceutical composition according to  claim 39 , wherein the animal is one of a mouse, a dog, and a cat. 
     
     
         41 . A food or drink comprising one of the following proteins (I) and (II):
 (I) an apoptosis inhibitor of macrophage; and   (II) a protein which consists of an amino acid sequence having deletion, substitution, or addition of one or more amino acids in an amino acid sequence of the apoptosis inhibitor of macrophage and having homology to the amino acid sequence of the apoptosis inhibitor of macrophage, and has a function of inhibiting differentiation of preadipocytes to mature adipocytes and/or a function of inducing lipolysis in the mature adipocytes.   
     
     
         42 . A method comprising producing the food or drink according to  claim 41 .