Caffeic acid phenethyl ester and its fluorinated derivative as natural anti-obesity agents

Objectives Caffeic acid phenethyl ester (CAPE), an active component of propolis from honeybee hives, is well studied for its beneficial effects on cancer, inflammation and diabetes. There are however limited studies investigating the effects of CAPE on obesity. Currently, several natural products are under investigation for their effects on adipocyte life cycle. A multi-targeted approach for prevention and treatment of obesity includes targeting adipocytes at all the stages of life cycle by decreasing adipocyte differentiation, inducing lipolysis and/or by inducing adipocyte apoptosis. In this study, we examined the effects of CAPE on preadipocyte viability, adipogenesis and lipolysis. Earlier reports on CAPE indicate that CAPE is liable to enzymatic hydrolysis in vivo making this compound unstable for therapeutic applications. In the current study, we compared the anti-adipogenic effects of CAPE with its novel fluorinated derivative (FCAPE), a more stable compound. Methods 3T3-L1 pre-adipocytes were differentiated using a cocktail consisting of insulin, dexamethasone, and isobutyl methyl xanthine in DMEM supplemented with 10% FBS following adipogeneic differentiation. Pre- and mature adipocytes were incubated with CAPE or FCAPE for 24-48 hours and their effects on viability, lipolysis, and adipogenesis was tested using Prestoblue, Lipolysis assay (Zen-Bio) and AdipoRed assay respectively. Results Our results indicate that neither CAPE nor FCAPE significantly altered preadipocyte viability within the tested dose range. Although both CAPE and FCAPE significantly decreased adipogenesis compared to control, FCAPE decreased lipid content by 73.6±1.6% while CAPE reduced lipid content by only 36.8±9.1% at 25μM concentration. In contrast to adipogenesis data, our preliminary results with lipolysis assay indicate that only CAPE, but not FCAPE induces lipolysis in mature adipocytes. Conclusions These findings suggest that both CAPE and FCAPE possess anti-adipogenic properties. Further studies are needed to elucidate their differential effects on adipogenesis and lipolysis. ObjectivesCaffeic acid phenethyl ester (CAPE), an active component of propolis from honeybee hives, is well studied for its beneficial effects oncancer, inflammation and diabetes. There are however limited studies investigating the effects of CAPE on obesity. Currently, severalnatural products are under investigation for their effects on adipocyte life cycle. A multi-targeted approach for prevention andtreatment of obesity includes targeting adipocytes at all the stages of life cycle by decreasing adipocyte differentiation, inducinglipolysis and/or by inducing adipocyte apoptosis. In this study, we examined the effects of CAPE on preadipocyte viability, adipogenesisand lipolysis. Earlier reports on CAPE indicate that CAPE is liable to enzymatic hydrolysis in vivo making this compound unstable fortherapeutic applications. In the current study, we compared the anti-adipogenic effects of CAPE with its novel fluorinated derivative(FCAPE), a more stable compound.Methods3T3-L1 pre-adipocytes were differentiated using a cocktail consisting of insulin, dexamethasone, and isobutyl methyl xanthine in DMEMsupplemented with 10% FBS following adipogeneic differentiation. Pre- and mature adipocytes were incubated with CAPE or FCAPE for24-48 hours and their effects on viability, lipolysis, and adipogenesis was tested using Prestoblue, Lipolysis assay (Zen-Bio) andAdipoRed assay respectively.ResultsOur results indicate that neither CAPE nor FCAPE significantly altered preadipocyte viability within the tested dose range. Although bothCAPE and FCAPE significantly decreased adipogenesis compared to control, FCAPE decreased lipid content by 73.6±1.6% while CAPEreduced lipid content by only 36.8±9.1% at 25μM concentration. In contrast to adipogenesis data, our preliminary results with lipolysisassay indicate that only CAPE, but not FCAPE induces lipolysis in mature adipocytes.ConclusionsThese findings suggest that both CAPE and FCAPE possess anti-adipogenic properties. Further studies are needed to elucidate theirdifferential effects on adipogenesis and lipolysis