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

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.

The Anti-Obesity and Anti-Inflammatory Capabilities of Pterostilbene and its Colonic Metabolite Pinostilbene Protect against Tight Junction Disruption from Western Diet Feeding.

SCOPE: Tight junctions (TJs) are a member of the intestinal epithelium barrier that provides the first line of protection against external factors. Anti-obesity and protective effects of pterostilbene (PSB) on TJs have previously been reported, but the effect of its colonic metabolite, pinostilbene (PIN), is less understood. METHODS AND RESULTS: A 16-week animal model feed with western-diet to induce colonic TJs disruption is designed, supplemented with PSB and PIN to evaluate their potent in colonic TJ protection. The results show that both PSB and PIN exert suppressive effects on obesity, hepatic steatosis, and chronic inflammation in western-diet-fed mice. Western-diet feeding significantly reduces expression of TJ proteins, including ZO-1, occludin, and claudin-1, while PSB and PIN supplementation effectively protects TJ proteins against disruption. Increment in serum, hepatic, and mesenteric pro-inflammatory cytokines suggests their probable involvement in TJ disruption supported with the findings in macrophage polarization. The adverse are revered by PSB and PIN. The protective effect of PSB and PIN on TJ proteins may stem from their anti-inflammation capabilities. CONCLUSION: This is the first study suggesting that PIN, the metabolite of PSB, demonstrates a similar protective effect on colonic TJ proteins via its anti-obesity, hepatic protection, and anti-inflammatory capabilities.