Oleuropein attenuates visceral adiposity in high‐fat diet‐induced obese mice through the modulation of WNT10b‐ and galanin‐mediated signalings

SCOPE: The aim of the present study was to investigate the antiobesity effect of oleuropein on high-fat diet (HFD) induced body weight gain and visceral adiposity in mice, and to explore the underlying mechanisms involved. METHODS AND RESULTS: C57BL/6N mice were fed with a normal diet, HFD (40% fat of total energy), and HFD-supplemented with 0.03% oleuropein for 10 wk. Oleuropein significantly reduced HFD-induced body weight gain and visceral adiposity. Oleuropein also significantly reversed the HFD-induced elevations of adipogenic related gene expression involved in WNT10b- and galanin-mediated signalings in adipose tissue of mice. Consistent with in vivo findings, oleuropein dose-dependently suppressed lipid accumulation in 3T3-L1 cells during preadipocyte differentiation. Additionally, exposure of the 3T3-L1 preadipocytes to oleuropein resulted in a marked attenuation of the secreted frizzled-related protein 2 (WNT inhibitor) or galnon (galanin receptor agonist) induced cellular lipid accumulation. CONCLUSION: This study demonstrated the oleuropein-reduced body weight gain and visceral adiposity in HFD-fed mice. The protective effect of oleuropein against HFD-induced adiposity in mice appeared to be mediated through the upregulation of genes involved in WNT10b-mediated signaling and downregulation of genes involved in galanin-mediated signaling cascades.