title: Additive regulation of adiponectin expression by the mediterranean diet olive oil components oleic Acid and hydroxytyrosol in human adipocytes.
abstract: Adiponectin, an adipocyte-derived insulin-sensitizing and anti-inflammatory hormone, is suppressed in obesity through mechanisms involving chronic inflammation and oxidative stress. Olive oil consumption is associated with beneficial cardiometabolic actions, with possible contributions from the antioxidant phenol hydroxytyrosol (HT) and the monounsaturated fatty acid oleic acid (OA, 18:1n-9 cis), both possessing anti-inflammatory and vasculo-protective properties. We determined the effects of HT and OA, alone and in combination, on adiponectin expression in human and murine adipocytes under pro-inflammatory conditions induced by the cytokine tumor necrosis factor(TNF)-α. We used human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes and murine 3T3-L1 adipocytes as cell model systems, and pretreated them with 1-100 μmol/L OA, 0.1-20 μmol/L HT or OA plus HT combination before stimulation with 10 ng/mL TNF-α. OA or HT significantly (P<0.05) prevented TNF-α-induced suppression of total adiponectin secretion (by 42% compared with TNF-α alone) as well as mRNA levels (by 30% compared with TNF-α alone). HT and OA also prevented-by 35%-TNF-α-induced downregulation of peroxisome proliferator-activated receptor PPARγ. Co-treatment with HT and OA restored adiponectin and PPARγ expression in an additive manner compared with single treatments. Exploring the activation of JNK, which is crucial for both adiponectin and PPARγ suppression by TNF-α, we found that HT and OA additively attenuated TNF-α-stimulated JNK phosphorylation (up to 55% inhibition). In conclusion, the virgin olive oil components OA and HT, at nutritionally relevant concentrations, have additive effects in preventing adiponectin downregulation in inflamed adipocytes through an attenuation of JNK-mediated PPARγ suppression.
authors.affiliation: National Research Council (CNR) Institute of Clinical Physiology, Lecce, Italy.
authors.forename: Egeria
authors.initials: E
authors.lastname: Scoditti
authors.affiliation: National Research Council (CNR) Institute of Clinical Physiology, Lecce, Italy.
authors.forename: Marika
authors.initials: M
authors.lastname: Massaro
authors.affiliation: National Research Council (CNR) Institute of Clinical Physiology, Lecce, Italy.
authors.forename: Maria Annunziata
authors.initials: MA
authors.lastname: Carluccio
authors.affiliation: Department of Biological and Environmental Science and Technology (DISTEBA), University of Salento, Lecce, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Pellegrino
authors.affiliation: Division of Pediatric Endocrinology, Diabetes and Obesity, Department of Pediatrics and Adolescent Medicine, University of Ulm, Ulm, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Wabitsch
authors.affiliation: National Research Council (CNR) Institute of Clinical Physiology, Lecce, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Calabriso
authors.affiliation: Department of Biological and Environmental Science and Technology (DISTEBA), University of Salento, Lecce, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Storelli
authors.affiliation: "G. d'Annunzio" University and Center of Excellence on Aging, Chieti, Italy; "G. Monasterio" Foundation for Clinical Research, Pisa, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Caterina
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics*; D000818:Animals; D038441:Diet, Mediterranean; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D019301:Oleic Acid / Q000494:pharmacology*; D000069463:Olive Oil / Q000737:chemistry*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D052242:Adiponectin; D000069463:Olive Oil; D047495:PPAR gamma; D014409:Tumor Necrosis Factor-alpha; C005975:3,4-dihydroxyphenylethanol; D019301:Oleic Acid; D048031:JNK Mitogen-Activated Protein Kinases; D010626:Phenylethyl Alcohol