USE OF INHIBITORS OF PLAC8 ACTIVITY FOR THE MODULATION OF ADIPOGENESIS
The present invention concerns Plac8, a new target involved in adipogenesis modulation. Using a siRNA approach, the inventors demonstrated that decrease in Plac8 activity in preadipocytes and adipose tissue induces a decrease in adipogenesis. Thus, the present invention relates to modulators of Plac8 activity as well screening test for identification of modulators as of the activity of this target, and their use, especially in pharmaceutical composition, to modulate adipogenesis and thus treat obesity and related disorders.
1 . An inhibitor of the activity of Plac8 for the modulation of adipogenesis.
2 . The inhibitor according to claim 1 which reduces adipogenesis.
3 . The inhibitor according to claim 2 for the treatment of obesity and related disorders.
4 . The inhibitor according to claim 2 for the reduction of visceral and/or subcutaneous fat accumulation.
5 . The inhibitor according to claim 2 wherein said inhibitor is a small molecule.
6 . The inhibitor according to claim 2 wherein said inhibitor is small interfering RNA (siRNA) molecule.
7 . The inhibitor according to claim 6 wherein the siRNA is a shRNA having a sequence corresponding to SEQ ID NO.5 or SEQ ID NO.6 or SEQ ID NO.7.
8 . (canceled)
9 . A nucleic acid comprising the sequence SEQ ID NO.6 or SEQ ID NO.7.
10 . The nucleic acid of claim 9 , wherein the nucleic acid is an siRNA specific for Plac8 transcriptional inhibition.
11 . A method for screening for inhibitors of the activity of Plac8 comprising:
a) transfecting a cell line with a reporter construction comprising a Plac8 promoter linked to a reporter gene
b) cultivating said cell line in condition to allow expression of the reporter gene
c) adding candidate compound into the cell culture, and
d) identifying inhibitor compounds as being those compounds which have the ability to reduce or inhibit the reporter gene expression
12 . A composition comprising an inhibitor of Plac8 activity and at least one pharmaceutically acceptable excipient.
13 . The composition according to claim 12 for treatment of obesity and related diseases.
14 . The composition according to claim 12 for reduction of visceral and/or subcutaneous fat accumulation.
15 . A method of modulation of adipogenesis comprising the step of administering to a patient in need thereof of an inhibitor of Plac8 to modulate adipogenesis.