Different routes of lipolysis as possible new therapeutic approaches of obesity

Abstract

Objective: obesity has increased worldwide, but there are currently few novel therapeutic options and the tendency to invasive procedures for the therapy of obesity and diabetes mellitus 2 are still an important risk. in order to assess the effect of compounds on the fat cell activity, we studied pre- clinically the activity of valproic acid, tricostatin a (histone deacetylase inhibitor) and eiD1 (eP300 inhibitor) which reduces the activity of PPar g, in a model of preadipocyte 3T3-l1 cells. Methods: transient transfections were performed with lipofectamine in 3T3-l1 and 293 cells. Unipotent 3T3-L1 cells underwent differentiation with the specific cocktail and the compounds were added to cells in physiological concentrations. We assessed the UCP1 expression through western blot, and the experiments were performed in triplicate. Results: we observed that the effect of tricostatin a was higher than that of the valproic acid in regard to lipolytic activity; however, both compounds exert an additive effect on eiD1 activity in adipose cell differentiation. eiD1 is able to stimulate the activity of protein UCP1, whose expression is characteristic of brown adipocyte. Conclusions: eiD1 is a reference protein to induce in the adipose cell higher caloric activity, reducing the accumulation of lipids in the adipocyte. The effect of valproic acid and tricostatin a can serve as a parameter for the search of new targeted therapeutic plans for obesity