Resveratrol Improves Mitochondrial Function and Protects against Metabolic Disease by Activating SIRT1 and PGC-1

Lagouge M, Argmann C, et al. Cell. 2006; 127(6): 1109-22

Abstract: In a study involving 4-8 week male mice, treatment with resveratrol (RSV) was found to significantly increase aerobic capacity, improve mitochondrial function, and protect against diet-induced obesity and insulin resistance. For a period of 15 weeks, male mice were fed a dose of 200 or 400 mg/kg/day (mpk) of resveratrol given either in a chow diet or high-fat diet. Plasma levels of resveratrol were dose-related, and ranged from 10 ng/ml to 120 ng/ml. Compared to controls that were not fed resveratrol, mice who received resveratrol gained less weight, which was significant in mice fed the high-fat diet. The authors discuss the effect of resveratrol on energy expenditure. Resveratrol was found to enhance adaptive thermogenesis. In mice, the majority of heat is produced by BAT (brown adipose tissue); resveratrol was found to increase larger BAT mitochondrial structures. Resveratrol was also found to increase resistance to muscle fatigue, increase muscle strength, and improve motor coordination and traction force, suggesting a beneficial effect on neuromuscular function. Fasting insulin levels were significantly reduced in resveratrol-fed mice. Glucose tolerance was also found to improve in a genetic mouse model of diabetes-obesity in animals fed resveratrol 400 mpk for 10 weeks, as compared to the same such mice not fed resveratrol. These results suggest that resveratrol may have potential to protect against weight gain and metabolic disorders.

Commentary: There continues to be excellent research on resveratrol, one of the major phenolic compounds found in red wine and red grape juice. This study is important because it demonstrates that resveratrol may enhance thermogenesis-the body's ability to burn calories, improve insulin resistance and metabolic syndrome, and improve glucose tolerance. This study also showed that this phenolic compound may also improve aspects of exercise tolerance and performance. It will be great to see if a supplement of resveratrol would have the same anti-obesity effect in humans. The levels of resveratrol that were given to the animals were quite large and would equate to about 14,000-28,000 mg being given to a 70 kg man. So clearly this would need to be repeated with a dose that would be reasonable.