The Anti-Obesity Effects of Xanthohumol Are Mediated Partly by the Adenosine Monophosphate-protein Kinase Signaling Pathway

Georgia

Xanthohumol (XN), a flavonoid compound extracted from the hop plant Humulus lupus, has been studied for its anti-cancer and anti-adipogenic effects. In this study, we have investigated the effects of XN on the inhibition of adipogenesis and the induction of browning in 3T3-L1 adipocytes. Furthermore, we provide evidence for the first time on the role of adenosine monophosphate-activated protein kinase (AMPK) signaling pathway in XN-induced anti-obesity effects. Browning of white adipose tissue, WAT, is emerging as a novel approach to address obesity. AMPK is activated in response to stress-like exposure to cold and has been shown to induce browning of WAT. 3T3-L1 preadipocytes were differentiated using a differentiating media supplemented with 10% FBS for 8-10 days following a standard differentiation protocol. Mature adipocytes were treated with either 0.01% DMSO or varying doses of XN for 24-48hrs. Treatment of mature 3T3-L1 adipocytes with XN 6.25µM and 25µM decreased lipid content during adipogenesis and increased the expression of uncoupling protein 1 (UCP1), in a dose-dependent manner in mature adipocytes. XN further increased mitochondrial activity in mature adipocytes. To demonstrate the role of AMPK pathway in XN-induced anti-obesity effects, mature adipocytes were treated with either 0.01% DMSO or XN 25µM in the presence or absence of dorsomorphin, an established inhibitor of the AMPK pathway, and AICAR, an AMPK stimulator. XN increased the expression of phospho-AMPK and this XN-induced increase in AMPK activation was diminished in the presence of dorsomorphin. In contrast, XN+AICAR demonstrated an additive effect on the activation of AMPK. Likewise, dorsomorphin reversed XN-induced inhibition of adipogenesis while XN+AICAR demonstrated an additive effect on the inhibition of lipid content during adipogenesis. These results provide evidence for the potential role of AMPK pathway in XN-induced anti-obesity effects in 3T3-L1 adipocytes.