Hydroxytyrosol Modulates Adipocyte Gene and miRNA Expression Under Inflammatory Condition

• Published in: Nutrients 2019-10, Vol.11 (10), p.2493
• Main Authors: Scoditti, Egeria, Carpi, Sara, Massaro, Marika, Pellegrino, Mariangela, Polini, Beatrice, Carluccio, Maria Annunziata, Wabitsch, Martin, Verri, Tiziano, Nieri, Paola, De Caterina, Raffaele
• Format: Article
• Language: English
• Subjects: adipocyte; Adipocytes; Adipocytes - drug effects; Adipocytes - metabolism; Adipogenesis; Angiogenesis; Antioxidants; Cell activation; Cell Line; Chemokines; Cyclooxygenase-2; Diabetes; Diet; DNA; Endocrinology; Endothelial cells; Ethanol; exosome; Exosomes - metabolism; extra virgin olive oil; Extracellular matrix; Gelatinase A; Gelatinase B; Gene expression; Gene Expression Regulation - drug effects; Gene regulation; Growth factors; High fat diet; Humans; hydroxytyrosol; Inflammation; Inflammation - chemically induced; Inflammation - metabolism; Insulin; insulin resistance; Intercellular adhesion molecule 1; Interleukin 6; Lipids; Maintenance; Matrix metalloproteinases; Metabolic syndrome; Metabolites; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Obesity; Oils & fats; Olive oil; Oxidative stress; Pediatrics; Phenylethyl Alcohol - analogs & derivatives; Phenylethyl Alcohol - pharmacology; Physiology; polyphenol; Polyphenols; Protein Binding; Reactive Oxygen Species; Scavenging; Transcription Factor RelA - metabolism; Tumor Necrosis Factor-alpha - pharmacology; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu11102493

Chronic inflammation of the adipose tissue (AT) is a major contributor to obesity-associated cardiometabolic complications. The olive oil polyphenol hydroxytyrosol (HT) contributes to Mediterranean diet cardiometabolic benefits through mechanisms still partially unknown. We investigated HT (1 and 10 μmol/L) effects on gene expression (mRNA and microRNA) related to inflammation induced by 10 ng/mL tumor necrosis factor (TNF)-α in human Simpson-Golabi-Behmel Syndrome (SGBS) adipocytes. At real-time PCR, HT significantly inhibited TNF-α-induced mRNA levels, of monocyte chemoattractant protein-1, C-X-C Motif Ligand-10, interleukin (IL)-1β, IL-6, vascular endothelial growth factor, plasminogen activator inhibitor-1, cyclooxygenase-2, macrophage colony-stimulating factor, matrix metalloproteinase-2, Cu/Zn superoxide dismutase-1, and glutathione peroxidase, as well as surface expression of intercellular adhesion molecule-1, and reverted the TNF-α-mediated inhibition of endothelial nitric oxide synthase, peroxisome proliferator-activated receptor coactivator-1α, and glucose transporter-4. We found similar effects in adipocytes stimulated by macrophage-conditioned media. Accordingly, HT significantly counteracted miR-155-5p, miR-34a-5p, and let-7c-5p expression in both cells and exosomes, and prevented NF-κB activation and production of reactive oxygen species. HT can therefore modulate adipocyte gene expression profile through mechanisms involving a reduction of oxidative stress and NF-κB inhibition. By such mechanisms, HT may blunt macrophage recruitment and improve AT inflammation, preventing the deregulation of pathways involved in obesity-related diseases.