Use of vgii3 activity modulator for the modulation of adipogenesis

Abstract

The present invention concerns Vgll3 a new target involved in adipogenesis modulation. Further, the present invention relates to methods to increase Vgll3 activity in adipocytes and preadipocytes. In addition, pharmaceutical composition comprising Vgll3 activity enhancing molecules in order to enhance the Vgll3 activity in a target tissue are also provided. These methods, compositions and molecules can be useful to modulate adipogenesis and thus treat obesity and related disorders.

1 . (canceled) 
     
     
         2 . A Vgll3 activity enhancing molecule that has a property selected from the group consisting of: reducing apidogenesis; treating obesity, hypertension, coronary artery disease, dyslipidemia, insulin resistance, type 2 diabetes, cardiovascular disorders, and metabolic syndrome; and reducing visceral fat accumulation, subcutaneous fat accumulation, or both visceral and subcutaneous fat accumulation. 
     
     
         3 . (canceled) 
     
     
         4 . (canceled) 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . A composition comprising a Vgll3 activity enhancing molecule and at least one pharmaceutically acceptable excipient. 
     
     
         11 . The composition according to  claim 10  for the preparation of a medicament to reduce adipogenesis. 
     
     
         12 . The composition according to  claim 10  for the preparation of a medicament to treat obesity, hypertension, coronary artery disease, dyslipidemia, insulin resistance, type 2 diabetes, cardiovascular disorders, and metabolic syndrome. 
     
     
         13 . The composition according to  claim 10  for the preparation of a medicament to reduce visceral and/or subcutaneous fat accumulation. 
     
     
         14 . (canceled) 
     
     
         15 . A method of screening for enhancers of the activity of Vgll3 comprising the steps of:
 a) transfecting a cell line with a reporter construction comprising a Vgll3 promoter linked to a reporter gene;   b) cultivating said cell line in condition to allow expression of the reporter gene;   c) adding candidate compounds into the cell culture; and   d) identifying enhancer compounds as being those compounds which have the ability to increase the reporter gene expression.   
     
     
         16 . The Vgll3 activity enhancing molecule of  claim 2 , wherein the Vgll3 activity enhancing molecule is a small molecule. 
     
     
         17 . The Vgll3 activity enhancing molecule of  claim 2 , wherein the Vgll3 activity enhancing molecule is a vector expressing a Vgll3 recombinant protein, 
     
     
         18 . The Vgll3 activity enhancing molecule of  claim 17 , wherein the vector comprises SEQ NO:15. 
     
     
         19 . The Vgll3 activity enhancing molecule of  claim 17 , wherein the Vgll3 recombinant protein comprises SEQ ID NO:2 or SEQ ID NO:4.