Hydroxytyrosol Modulates Adipocyte Gene and miRNA Expression Under Inflammatory Condition

Nutrients

Raffaele De Caterina¹  Martin Wabitsch²  Mariangela Pellegrino³  Tiziano Verri³  Sara Carpi⁴  Beatrice Polini⁴  Paola Nieri⁴  Marika Massaro⁵  MariaAnnunziata Carluccio⁵  Egeria Scoditti⁵ 

[1] Cardiology Division, Pisa University Hospital, 56126 Pisa, Italy;Division of Pediatric Endocrinology, Diabetes and Obesity, Department of Pediatrics and Adolescent Medicine, University of Ulm, 89075 Ulm, Germany;Laboratory of Applied Physiology, Department of Biological and Environmental Science and Technology (DISTEBA), University of Salento, 73100 Lecce, Italy;Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Pisa, 56126 Pisa, Italy;National Research Council (CNR) Institute of Clinical Physiology (IFC), 73100 Lecce, Italy;

关键词: adipocyte;    exosome;    gene expression;    hydroxytyrosol;    inflammation;    insulin resistance;    extra virgin olive oil;    mirna;    obesity;    polyphenol;   

DOI  :  10.3390/nu11102493

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown