Resveratrol and Oxyresveratrol Activate Thermogenesis via Different Transcriptional Coactivators in High-Fat Diet-Induced Obese Mice

Obesity is a global public health issue. Thermogenesis is a novel way to promote anti-obesity by consuming energy as heat rather than storing it as triacylglycerols. The browning program allows mitochondrial biosynthesis and thermogenesis-related gene expression to occur in subcutaneous white adipose tissue, which results in the formation of beige adipose tissue. Some phytochemicals have exerted the capability to activate the fat browning process. Resveratrol and oxyresveratrol are both natural stilbenoids that have been reported for their anti-obesity efficacy. However, the comparison between the two as they relate to thermogenesis as well as the differences in their underlying mechanisms are still not widely discussed. Our result reveals that both resveratrol and oxyresveratrol could elevate the expression of thermogenesis-related protein expression including UCP1 (uncoupling protein-1) and PRDM (PR domain containing 16) via Sirt1/PGC-1α (sirtuin 1/peroxisome proliferation gamma coactivator-1 α) activation. However, it is suggested that the transcriptional factor PPARα (peroxisome proliferator-activator receptor α) was activated by resveratrol (1.38 ± 0.07 fold) but not oxyresveratrol. Conversely, C/EBPβ (CCAAT/enhancer-binding protein β) was upregulated by oxyresveratrol (1.58 ± 0.05 fold) but not by resveratrol. On the other hand, CPT1 (carnitine palmitoyltransferase) was found to be significantly activated at lower concentrations of oxyresveratrol up to 1.89 ± 0.04 fold as compared to high-fat diet, and it could be a leading reason for UCP1 activation. Lastly, adiponectin expression was promoted in all experimental groups (1.53 ± 0.08 and 1.49 ± 0.11-fold in resveratrol (RES) and high oxyresveratrol (HOXY), respectively), which could be an activator for mitochondrial biosynthesis and UCP1 expression.