AMPK modulatory activity of olive-tree leaves phenolic compounds: Bioassay-guided isolation on adipocyte model and in silico approach

• Published in: PloS one Vol. 12; no. 3; p. e0173074
• Main Authors: Jiménez-Sánchez, Cecilia, Olivares-Vicente, Mariló, Rodríguez-Pérez, Celia, Herranz-López, María, Lozano-Sánchez, Jesús, Segura-Carretero, Antonio, Fernández-Gutiérrez, Alberto, Encinar, José Antonio, Micol, Vicente
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09-03-2017; Public Library of Science (PLoS)
• Subjects: 3T3-L1 Cells; Accumulation; Adipocytes; Adipocytes - cytology; Adipocytes - drug effects; Adipocytes - metabolism; AMP-activated protein kinase; AMP-Activated Protein Kinases - analysis; AMP-Activated Protein Kinases - chemistry; AMP-Activated Protein Kinases - metabolism; Analysis; Analytical chemistry; Animals; Binding Sites; Bioassays; Biology and Life Sciences; Care and treatment; Chromatography; Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Cinnamic acid; Energy; Flavonoids; Food; Fractionation; Fruit trees; Functional foods & nutraceuticals; Gene Expression Regulation - drug effects; Health aspects; Herbal medicine; High performance liquid chromatography; Homeostasis; Immunofluorescence; Immunomodulation; Intracellular; Ionization; Kinases; Leaves; Lignans; Liquid chromatography; Medicine and Health Sciences; Metabolism; Mice; Microscopy; Microscopy, Fluorescence; Modulators; Molecular docking; Molecular Docking Simulation; Obesity; Olea - chemistry; Olea - metabolism; Olea europaea; Olives; Phenolic compounds; Phenols; Phenylpropanoids; Phosphorylation; Physical Sciences; Physiological aspects; Plant Extracts - analysis; Plant Extracts - chemistry; Plant Leaves - chemistry; Plant Leaves - metabolism; Polyphenols; Polyphenols - chemistry; Polyphenols - isolation & purification; Polyphenols - metabolism; Polyphenols - pharmacology; Protein kinases; Protein Structure, Tertiary; Protein Subunits - analysis; Protein Subunits - metabolism; Proteins; R&D; Research & development; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Triglycerides; Triglycerides - analysis; Triglycerides - metabolism; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0173074

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.
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.
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.
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.