Tyrosol May Prevent Obesity by Inhibiting Adipogenesis in 3T3-L1 Preadipocytes.

Abstract

Tyrosol (TR), a major polyphenol found in extra virgin olive oil (EVOO), exerts several antioxidant effects. However, only scarce evidences are present regarding its activity on adipocytes and obesity. This study evaluated the role of TR in adipogenesis. Murine 3T3-L1 preadipocytes were incubated with TR (300 and 500 μM), and TR administration inhibited adipogenesis by downregulation of several adipogenic factors (leptin and aP2) and transcription factors (C/EBPα, PPARγ, SREBP1c, and Glut4) and by modulation of the histone deacetylase sirtuin 1. After complete differentiation, adipocytes treated with 300 and 500 μM TR showed a reduction of 20% and 30% in lipid droplets, respectively. Intracellular triglycerides were significantly reduced after TR treatment (p < 0.05). Mature adipocytes treated with TR at 300 and 500 μM showed a marked decrease in the inflammatory state and oxidative stress as shown by the modulation of specific biomarkers (TNF, IL6, ROS, and SOD2). TR treatment also acted on the early stage of differentiation by reducing cell proliferation (~40%) and inducing cell cycle arrest during Mitotic Expansion Clonal (first 48 h of differentiation), as shown by the increase in both S1 phase and p21 protein expression. We also showed that TR induced lipolysis by activating the AMPK-ATGL-HSL pathway. In conclusion, we provided evidence that TR reduces 3T3-L1 differentiation through downregulation of adipogenic proteins, inflammation, and oxidative stress. Moreover, TR may trigger adipose tissue browning throughout the induction of the AMPK-ATGL-UCP1 pathway and, subsequently, may have promise as a potential therapeutic agent for the treatment and prevention of obesity.

• Authors: Francesca Pacifici, Carolina Lane Alves Farias, Silvia Rea, Barbara Capuani, Alessandra Feraco, Andrea Coppola, Caterina Mammi, Donatella Pastore, Pasquale Abete, Valentina Rovella, Chiara Salimei, Mauro Lombardo, Massimiliano Caprio, Alfonso Bellia, Paolo Sbraccia, Nicola Di Daniele, Davide Lauro, David Della-Morte
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2020 Pg. 4794780 ( 2020) ISSN: 1942-0994 [Electronic] United States
• PMID: 33376578 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Francesca Pacifici et al.

Chemical References

• 4-hydroxyphenylethanol
• Phenylethyl Alcohol

Topics

• 3T3-L1 Cells
• Adipocytes (metabolism, pathology)
• Adipogenesis (drug effects)
• Animals
• Gene Expression Regulation (drug effects)
• Mice
• Obesity (metabolism, pathology, prevention & control)
• Phenylethyl Alcohol (analogs & derivatives, pharmacology)