Effects of Quercetin Metabolites on Glucose-Dependent Lipid Accumulation in 3T3-L1 Adipocytes

The aim of the study was to assess the effects of quercetin metabolites (QMs) on lipid accumulation in adipocytes under high-glucose and physiological-glucose concentrations and to elucidate the mechanisms involved. 3T3-L1 mature adipocytes were exposed to a physiological glucose concentration, as a model of caloric restriction (CR), or high glucose (control), with and without QMs (quercetin-3-glucuronide [Q3G] and isorhamnetin [ISOR]). Cells were treated with Q3G (0.3 and 0.6 mu mol/L) and ISOR (0.2 and 0.4 mu mol/L) for 48 h. Lipid accumulation (Oil Red O staining) and Delta glucose level (HPLC) were assessed. Under high glucose, Q3G and ISOR reduced lipid accumulation (-10.8% and -10.4%; p < 0.01) and Delta glucose level (-13.6% and -14.2%; p < 0.05). Under CR, QMs increased Delta glucose level (+21.6% for Q3G and +21% for ISOR; p < 0.05). ISOR increased pAMPK levels under high glucose (+1.4-fold; p < 0.05). Under CR, Q3G and ISOR increased pAMPK (+1.4- and +1.5-fold; p < 0.05), while ISOR upregulated SIRT1 and PGC-1 alpha (+2.3- and +1.5-fold; p < 0.05). Findings support, for the first time, the potential contribution of QMs, especially ISOR, in the regulation of lipid metabolism in vitro, possibly via AMPK activation. Further studies, including in vivo, are encouraged to strengthen evidence of the mechanisms observed.