Use of inhibitors of zdhhc2 activity for modulation of adipogenesis

Abstract

The present invention concerns Zdhhc2, a new target involved in adipogenesis modulation. Using a siRNA approach, the inventors demonstrated that decrease in Zdhhc2 activity in adipose tissue induces a decrease in adipogenesis. Thus, the present invention relates to modulators of Zdhhc2 activity as well as screening test for identification of modulators of the activity of this target, and their use, especially in pharmaceutical composition, to modulate adipogenesis and thus treat obesity and related disorders.

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         8 . A nucleic acid comprising a siRNA specific for Zinc finger, DHHC-type containing 2 protein (Zdhhc2) transcriptional inhibition. 
     
     
         9 . The nucleic acid of  claim 8 , wherein the nucleic acid comprises the nucleic acid sequence of SEQ ID NO: 5 or SEQ ID NO: 6. 
     
     
         10 . A method for identifying a compound able to modulate the enzymatic activity of Zinc finger, DHHC-type containing 2 protein (Zdhhc2) comprising:
 a) providing a sample containing Zdhhc2 activity;   b) adding a candidate compound to the sample;   c) measuring the activity of palmitoylation in the sample;   d) comparing the activity of palmitoylation in the sample to the activity of palmitoylation in a control; and   e) identifying the candidate compound as a compound able to modulate enzymatic activity of Zdhhc2 when the activity of palmitoylation in the sample is decreased compared to the activity of palmitoylation in the control.   
     
     
         11 . A composition comprising an inhibitor of Zinc finger, DHHC-type containing 2 protein (Zdhhc2) activity and at least one pharmaceutically acceptable excipient. 
     
     
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         16 . The composition of  claim 11 , wherein the inhibitor is a nucleic acid comprising a siRNA specific for Zdhhc2 transcriptional inhibition. 
     
     
         17 . The composition of  claim 16 , wherein the nucleic acid comprises the nucleic acid sequence of SEQ ID NO: 5 or SEQ ID NO: 6.