Pterostilbene Enhances Thermogenesis and Mitochondrial Biogenesis by Activating the SIRT1/PGC-1α/SIRT3 Pathway to Prevent Western Diet-Induced Obesity

Mol Nutr Food Res. 2023 Sep;67(18):e2300370. doi: 10.1002/mnfr.202300370. Epub 2023 Jul 23.

Abstract

Scope: Sirtuin 1/peroxisome proliferator-activated receptor gamma co-activator 1 alpha (SIRT1/PGC-1α) pathway activation is known to promote thermogenesis and mitochondrial biogenesis. Pterostilbene (PSB) and pinostilbene (PIN), the methylated analogs of resveratrol, are potential candidates to enhance thermogenesis and mitochondrial biogenesis.

Method and results: A model of Western diet-induced obesity in mice is designed. Either PSB or PIN is supplemented in the diet for 16 weeks. Both samples can significantly reduce body weight gain but only PSB can decrease inguinal adipose tissue weight. Besides, both samples can promote lipolysis but only PSB supplementation activates the SIRT1/PGC-1α/SIRT3 pathway to enhance mitochondrial biogenesis and thermogenesis in the inguinal adipose tissue. In addition, although both samples exert a modulatory effect on gut microbiota but significant increments in fecal isobutyric acid, valeric acid, and isovaleric acid are only observed in the PSB group, functioning as gut microbial metabolites.

Conclusion: Overall, these findings suggest PSB and PIN as potential candidates for the improvement of obesity and gut microbiota dysbiosis. With its higher stability, PSB exerts a greater effect than PIN by promoting thermogenesis and mitochondrial biogenesis via SIRT1 activation.

Keywords: SIRT1; mitochondrial biogenesis; pinostilbene; pterostilbene; thermogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diet, Western
  • Mice
  • Mitochondria
  • Obesity / etiology
  • Obesity / metabolism
  • Organelle Biogenesis
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Sirtuin 1 / metabolism
  • Sirtuin 3* / metabolism
  • Thermogenesis
  • Transcription Factors* / metabolism

Substances

  • Transcription Factors
  • Sirtuin 3
  • Sirtuin 1
  • pterostilbene
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha