title: Correlation between the cellular metabolism of quercetin and its glucuronide metabolite and oxidative stress in hypertrophied 3T3-L1 adipocytes.
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.
  
  
  OBJECTIVE
  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 ± 0.03µg/µg protein) and faster than that of Q3GA (0.12 ± 0.0015µg/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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Molecular and Cell Biology (IMCB), Miguel Hernández University (UMH), Elche 03202, Alicante, Spain. Electronic address: mherranz@umh.es.
authors.forename: María
authors.initials: M
authors.lastname: Herranz-López
authors.affiliation: Center for Research and Development of Functional Food (CIDAF), Science Technology Park Health, Armilla, Granada, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Borrás-Linares
authors.affiliation: Institute of Molecular and Cell Biology (IMCB), Miguel Hernández University (UMH), Elche 03202, Alicante, Spain.
authors.forename: Mariló
authors.initials: M
authors.lastname: Olivares-Vicente
authors.affiliation: CIBER-EHD, Department of Pharmacology, Center for Biomedical Research (CIBM), University of Granada, Avenida del Conocimiento s/n 18016, Armilla, Granada, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Gálvez
authors.affiliation: Center for Research and Development of Functional Food (CIDAF), Science Technology Park Health, Armilla, Granada, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Segura-Carretero
authors.affiliation: Institute of Molecular and Cell Biology (IMCB), Miguel Hernández University (UMH), Elche 03202, Alicante, Spain; CIBER, Fisiopatología de la Obesidad y la Nutrición, CIBERobn, Instituto de Salud Carlos III (CB12/03/30038), Spain. Electronic address: vmicol@umh.es.
authors.forename: Vicente
authors.initials: V
authors.lastname: Micol
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D020719:Glucuronides / Q000378:metabolism; D031584:Hibiscus / Q000737:chemistry; D006801:Humans; D006984:Hypertrophy; D051379:Mice; D009765:Obesity / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D011794:Quercetin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D020719:Glucuronides; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D011794:Quercetin
keywords: Adipocytes; Cellular metabolism; HPLC-DAD-ESI-TOF; Quercetin; Quercetin-3-O-β-D-glucuronide; ROS