Lsr receptor, its activity, its cloning, and its applications to the diagnosis, prevention and/or treatment of obesity and related risks or complications

Abstract

The present invention relates to a new complex receptor polypeptide LSR (Lipolysis Stimulated Receptor), characterized by its functional activities, the cloning of the cDNAs complementary to the messenger RNAs encoding each of the subunits of the multimeric complex, vectors and transformed cells, methods of diagnosis and of selection of compounds which can be used as medicament for the prevention and/or treatment of pathologies and/or of pathogeneses such as obesity and anorexia, hyperlipidemias, atherosclerosis, diabetes, hypertension, and more generally the various pathologies associated with abnormalities in the metabolism of cytokines.

1 . A composition of matter comprising:
 a) a purified polypeptide comprising at least 10 to 15 consecutive amino acids of SEQ ID NO: 2, 4, 6, 10, 16, 17 or 18 or comprising a polypeptide that is at least 90% identical to SEQ ID NO: 2, 4, 6, 10, 16, 17 or 18;   b) a purified nucleic acid sequence comprising: SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 14 or 15; or encoding: a polypeptide comprising at least 10 to 15 consecutive amino acids of SEQ ID NO: 2, 4, 6, 8, 10, 12, 16, 17 or 18; or comprising a polypeptide that is at least 90% identical to SEQ ID NO: 2, 4, 6, 8, 10, 12, 16, 17 or 18;   c) a vector comprising a nucleic acid comprising SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 14 or 15 or encoding: a polypeptide comprising at least 10 to 15 consecutive amino acids of SEQ ID NO: 2, 4, 6, 8, 10, 12, 16, 17 or 18; or comprising a polypeptide that is at least 90% identical to SEQ ID NO: 2, 4, 6, 8, 10, 12, 16, 17 or 18;   d) a recombinant cell comprising:
 i) SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 14 or 15; 
 ii) a vector comprising SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 14 or 15; or 
 iii) a nucleic sequence encoding: a polypeptide comprising at least 10 to 15 consecutive amino acids of SEQ ID NO: 2, 4, 6, 8, 10, 12, 16, 17 or 18; or comprising a polypeptide that is at least 90% identical to SEQ ID NO: 2, 4, 6, 8, 10, 12, 16, 17 or 18; or 
   e) an isolated antibody that specifically binds to a polypeptide comprising at least 10 to 15 consecutive amino acids of SEQ ID NO: 2, 4, 6, 16, 17 or 18.   
     
     
         2 . The composition of matter according to  claim 1 , wherein said polypeptide is a purified or recombinant Lipolysis Stimulated Receptor and said receptor comprises at least 10 to 15 consecutive amino acids of SEQ ID NO: 2, 4, 6, 10, 16, 17 or 18. 
     
     
         3 . The composition of matter according to  claim 1 , wherein said polypeptide comprises at least 10 to 15 consecutive amino acids of SEQ ID NO: 2, 4, 6, 10, 16, 17 or 18. 
     
     
         4 . The composition of matter according to  claim 3 , wherein said polypeptide comprises SEQ ID NO: 2, 4, 6, 10, 16, 17 or 18. 
     
     
         5 . The composition of matter according to  claim 1 , wherein said polypeptide is at least 90% identical to SEQ ID NO: 2, 4, 6, 10, 16, 17 or 18. 
     
     
         6 . The composition of matter according to  claim 5 , wherein said polypeptide comprises SEQ ID NO: 2, 4, 6, 10, 16, 17 or 18. 
     
     
         7 . The composition of matter according to  claim 1 , wherein said nucleic acid encodes polypeptide comprising at least 10 to 15 consecutive amino acids of SEQ ID NO: 2, 4, 6, 8, 10, 12, 16, 17 or 18. 
     
     
         8 . The composition of matter according to  claim 1 , wherein said nucleic acid encodes a polypeptide that is at least 90% identical to SEQ ID NO: 2, 4, 6, 8, 10, 12, 16, 17 or 18. 
     
     
         9 . The composition of matter according to  claim 1 , wherein said nucleic acid encodes SEQ ID NO: 2, 4, 6, 8, 10, 12, 16, 17 or 18. 
     
     
         10 . The composition of matter according to  claim 1 , wherein said nucleic acid is SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 14 or 15. 
     
     
         11 . A method for selecting a compound useful for enhancing lipoprotein uptake in cells comprising the steps:
 a) contacting the recombinant cell of  claim 1  with a candidate compound in the presence of a lipoprotein; and   b) determining whether the amount of internalized lipoprotein is greater in the presence of said compound than in the absence of said compound, wherein a determination that said amount of internalized lipoprotein is greater in the presence of said compound indicates that said compound is useful for enhancing lipoprotein uptake in cells.   
     
     
         12 . The method according to  claim 11 , wherein said candidate compound is a small molecule. 
     
     
         13 . A method for selecting a compound useful for enhancing lipoprotein uptake in cells comprising the steps:
 a) contacting the recombinant cell of  claim 1  with a candidate compound in the presence of a lipoprotein; and   b) determining whether the amount of internalized lipoprotein is greater in the presence of said compound than in the absence of said compound, wherein a determination that said amount of internalized lipoprotein is greater in the presence of said compound indicates that said compound is useful for enhancing lipoprotein uptake in cells.   
     
     
         14 . The method according to  claim 13 , wherein said candidate compound is a small molecule. 
     
     
         15 . A composition comprising the composition of matter according to  claim 1  and a physiologically acceptable carrier. 
     
     
         16 . A method of making a polypeptide comprising:
 a) obtaining a recombinant cell according to  claim 1  that expresses said polypeptide;   b) growing said recombinant cells under conditions suitable to produce said polypeptide; and   c) isolating said polypeptide produced by said recombinant cell.   
     
     
         17 . The method according to  claim 16 , wherein said cell is prokaryotic. 
     
     
         18 . The method according to  claim 16 , wherein said cell is eukaryotic. 
     
     
         19 . The method according to  claim 16 , further comprising purifying said polypeptide produced by said cell.