The Anti-Obesity Effects of Xanthohumol Are Partly Mediated by the Adenosine Monophosphate-activated Protein Kinase Signaling Pathway
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 onthe 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 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 cocktail comprised of insulin, dexamethasone, isobutyl methyl xanthine and rosiglitazone in DMEM supplemented with 10% FBS following an 8 - 10 day adipogenic 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 6.25 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 after 24 hours suggesting browning of 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 AMPK pathway and 5-Aminoimidazole-4-carboxamide ribonucleotide (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. On the other hand, 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.
Samuels, J.; Fitch, Z.; Chae, H.-G.; and Rayalam, Srujana, "The Anti-Obesity Effects of Xanthohumol Are Partly Mediated by the Adenosine Monophosphate-activated Protein Kinase Signaling Pathway" (2017). PCOM Scholarly Papers. 1878.