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 25 μM 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. Funding Sources This study was funded by the Department of Research, PCOM.

Xanthohumol (XN), a prenylated chalcone extracted from common hop plants, has been studied for its anti-inflammatory properties. In this study, we hypothesize that XN induces M2 polarization of macrophages and the resulting anti-inflammatory effects are mediated through the activation of adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. RAW 264.7 cells were treated with either 0.1% DMSO or XN and the culture supernatant was collected for ELISA and whole cell lysates were collected for western blotting. Our results demonstrate that XN upregulated the secretion of IL10, a signature cytokine for M2 polarization, in RAW264.7 cells. We further demonstrated that XN increased arginase expression, a marker for M2 polarization, and suppressed IFNγ-mediated upregulation of inducible nitric oxide synthase (iNOS) expression, a marker for M1 polarization. Additionally, XN decreased IFNγ – induced elevation of nitrite release, indicating the inhibitory effects of XN against M1 polarization. Furthermore, XN at 25μM increased the secretion of catecholamines from macrophages comparable to IL4, an inducer of M2 phenotype and these effects were accompanied by an increased expression of tyrosine hydroxylase, a rate-limiting enzyme of catecholamine biosynthesis. Finally, XN and AICAR, an AMPK stimulator, upregulated the expression of phospho-AMPK and arginase while dorsomorphin, an established inhibitor of the AMPK pathway failed to do so in RAW264.7 cells. These results provide evidence for the anti-inflammatory effects of XN mediated through the induction of M2 polarization and activation of AMPK signaling pathway.