Pterostilbene induces browning of white adipocytes via AMPK/PGC-1α pathway

Abstract

Background: Many studies have demonstrated that certain dietary polyphenols exert anti-obesity effects by increasing energy expenditure as heat via activating brown adipose and/or browning of white adipose. Pterostilbene, a resveratrol dimethyl ether analogue, has been demonstrated to have anti-obesity effects. However, studies on the mechanisms by which pterostilbene exert anti-obesity effect are still inadequate. As such, the current study tests the hypothesis that pterostilbene administration induces browning of white adipose, thus controlling body weight gain. Method: The effects of pterostilbene administration on white adipocytes browning in inguinal white adipose tissue (iWAT) of rats and 3T3-L1 adipocytes as well as their underlying mechanisms were investigated in the current study. Results: The administration of pterostilbene for 8 weeks reduced rats’ body weight gain and iWAT index. Furthermore, pterostilbene increased the content of mitochondria and the expression of brown and beige adipocyte markers such as uncoupling protein 1 (UCP1), PR domain-containing 16 (PRDM16), and transmembrane protein 26 (TMEM26) in iWAT. Pterostilbene treatment also activated AMP-activated protein kinase (AMPK) and increased expression of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α) in iWAT. In agreement with the in vivo findings, the in vitro results showed that 1 μM pterostilbene treatment also activated AMPK and increased PGC-1α expression, and stimulated formation of brown-like adipocytes as evidenced by the increased mitochondria content and expression of brown and beige adipocytes markers in 3T3-L1 adipocytes. However, those positive effects of pterostilbene on 3T3-L1 adipocytes were significantly inhibited by pretreatment with an AMPK inhibitor (compound C) or PGC-1α siRNA. Conclusion: These findings suggest that pterostilbene exerts body weight gain-lowering effect by inducing white adipocytes browning via the AMPK/PGC-1α pathway.