Correlation between the cellular metabolism of quercetin and its glucuronide metabolite and oxidative stress in hypertrophied 3T3-L1 adipocytes
2017
Abstract Background Quercetin (Q) is one of the most abundant flavonoids in human dietary sources and has been related to the capacity to ameliorate obesity-related pathologies. Quercetin-3-O-β- d -glucuronide (Q3GA) is supposed to be the main metabolite in blood circulation, but the intracellular final effectors for its activity are still unknown. Hypothesis/purpose To identify and quantitate the intracellular metabolites in hypertrophied adipocytes incubated with Q or Q3GA and to correlate them with the intracellular generation of oxygen radical species (ROS). Methods Cytoplasmic fractions were obtained and quercetin metabolites were determined by liquid chromatography coupled to a time-of-flight mass detector with electrospray ionization (HPLC-DAD-ESI-TOF). Intracellular ROS generation was measured by a ROS-sensitive fluorescent probe. Results Both Q and Q3GA were absorbed by hypertrophied adipocytes and metabolized to some extent to Q3GA and Q, respectively, but Q absorption was more efficient (1.92 ± 0.03 µg/µg protein) and faster than that of Q3GA (0.12 ± 0.0015 µg/µg protein), leading to a higher intracellular concentration of the aglycone. Intracellular decrease of ROS correlated with the presence of the most abundant quercetin metabolite. Conclusion Q and Q3GA are efficiently absorbed by hypertrophied adipocytes and metabolized to some extent to Q3GA and Q, respectively. The intracellular decrease of ROS in a hypertrophied adipocyte model treated with Q or Q3GA is correlated with the most abundant intracellular metabolite for the first time. Both compounds might be able to reach other intracellular targets, thus contributing to their bioactivity.
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