title: AMPK modulatory activity of olive-tree leaves phenolic compounds: Bioassay-guided isolation on adipocyte model and in silico approach.
abstract: METHODS
  Olive-tree polyphenols have demonstrated potential for the management of obesity-related pathologies. We aimed to explore the capacity of Olive-tree leaves extract to modulate triglyceride accumulation and AMP-activated protein kinase activity (AMPK) on a hypertrophic adipocyte model.
  
  
  METHODS
  Intracellular triglycerides and AMPK activity were measured on the hypertrophic 3T3-L1 adipocyte model by AdipoRed and immunofluorescence microscopy, respectively. Reverse phase high performance liquid chromatography coupled to time-of-flight mass detection with electrospray ionization (RP-HPLC-ESI-TOF/MS) was used for the fractionation of the extract and the identification of the compounds. In-silico molecular docking of the AMPK alpha-2, beta and gamma subunits with the identified compounds was performed.
  
  
  RESULTS
  Olive-tree leaves extract decreased the intracellular lipid accumulation through AMPK-dependent mechanisms in hypertrophic adipocytes. Secoiridoids, cinnamic acids, phenylethanoids and phenylpropanoids, flavonoids and lignans were the candidates predicted to account for this effect. Molecular docking revealed that some compounds may be AMPK-gamma modulators. The modulatory effects of compounds over the alpha and beta AMPK subunits appear to be less probable.
  
  
  CONCLUSIONS
  Olive-tree leaves polyphenols modulate AMPK activity, which may become a therapeutic aid in the management of obesity-associated disturbances. The natural occurrence of these compounds may have important nutritional implications for the design of functional ingredients.
authors.affiliation: Department of Analytical Chemistry, University of Granada. Granada, Spain.|Research and Development of Functional Food Centre (CIDAF), PTS, Granada, Spain.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Jiménez-Sánchez
authors.affiliation: Instituto de Biología Molecular y Celular (IBMC), Miguel Hernández University (UMH), Elche, Alicante, Spain.
authors.forename: Mariló
authors.initials: M
authors.lastname: Olivares-Vicente
authors.affiliation: Department of Analytical Chemistry, University of Granada. Granada, Spain.|Research and Development of Functional Food Centre (CIDAF), PTS, Granada, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Rodríguez-Pérez
authors.affiliation: Instituto de Biología Molecular y Celular (IBMC), Miguel Hernández University (UMH), Elche, Alicante, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Herranz-López
authors.affiliation: Department of Analytical Chemistry, University of Granada. Granada, Spain.|Research and Development of Functional Food Centre (CIDAF), PTS, Granada, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Lozano-Sánchez
authors.affiliation: Department of Analytical Chemistry, University of Granada. Granada, Spain.|Research and Development of Functional Food Centre (CIDAF), PTS, Granada, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Segura-Carretero
authors.affiliation: Department of Analytical Chemistry, University of Granada. Granada, Spain.|Research and Development of Functional Food Centre (CIDAF), PTS, Granada, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Fernández-Gutiérrez
authors.affiliation: Instituto de Biología Molecular y Celular (IBMC), Miguel Hernández University (UMH), Elche, Alicante, Spain.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Encinar
authors.affiliation: Instituto de Biología Molecular y Celular (IBMC), Miguel Hernández University (UMH), Elche, Alicante, Spain.|CIBER: CB12/03/30038, Fisiopatología de la Obesidad y la Nutrición, CIBERobn, Instituto de Salud Carlos III (ISCIII), Palma de Mallorca, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Micol
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D005786:Gene Expression Regulation / Q000187:drug effects*; D051379:Mice; D008856:Microscopy, Fluorescence; D062105:Molecular Docking Simulation; D031658:Olea / Q000737:chemistry* / Q000378:metabolism; D010936:Plant Extracts / Q000032:analysis / Q000737:chemistry; D018515:Plant Leaves / Q000737:chemistry / Q000378:metabolism; D059808:Polyphenols / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000032:analysis / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014280:Triglycerides / Q000032:analysis / Q000378:metabolism
chemical_list: D010936:Plant Extracts; D059808:Polyphenols; D021122:Protein Subunits; D014280:Triglycerides; D055372:AMP-Activated Protein Kinases