Estudios científicos
AMP-activated protein kinase-deficient mice are resistant to the metabolic effects of resveratrol
Abstract:
OBJECTIVE: Resveratrol, a natural polyphenolic compound that is found in grapes and red wine, increases metabolic rate, insulin sensitivity, mitochondrial biogenesis, and physical endurance and reduces fat accumulation in mice. Although it is thought that resveratrol targets Sirt1, this is controversial because resveratrol also activates 5' AMP-activated protein kinase (AMPK), which also regulates insulin sensitivity and mitochondrial biogenesis. Here, we use mice deficient in AMPKalpha1 or -alpha2 to determine whether the metabolic effects of resveratrol are mediated by AMPK. RESEARCH DESIGN AND METHODS: Mice deficient in the catalytic subunit of AMPK (alpha1 or alpha2) and wild-type mice were fed a high-fat diet or high-fat diet supplemented with resveratrol for 13 weeks. Body weight was recorded biweekly and metabolic parameters were measured. We also used mouse embryonic fibroblasts deficient in AMPK to study the role of AMPK in resveratrol-mediated effects in vitro. RESULTS: Resveratrol increased the metabolic rate and reduced fat mass in wild-type mice but not in AMPKalpha1(-/-) mice. In the absence of either AMPKalpha1 or -alpha2, resveratrol failed to increase insulin sensitivity, glucose tolerance, mitochondrial biogenesis, and physical endurance. Consistent with this, the expression of genes important for mitochondrial biogenesis was not induced by resveratrol in AMPK-deficient mice. In addition, resveratrol increased the NAD-to-NADH ratio in an AMPK-dependent manner, which may explain how resveratrol may activate Sirt1 indirectly. CONCLUSIONS: We conclude that AMPK, which was thought to be an off-target hit of resveratrol, is the central target for the metabolic effects of resveratrol
Comentarios divulgativos:
El resveratrol es un compuesto polifenólico que se encuentra en uvas y vino tinto y que incrementa la sensibilidad a la insulina, la biogénesis de mitocondrias y reduce la acumulación de grasa en ratones. Aunque se ha descrito que el resveratrol es la diana de Sirt1, esto es muy controvertido porque el resveratrol también activa a la 5 AMP proteina kinasa (AMPK). En este estudio se usan ratones deficiwentes en AMPK alfa1 o alfa2 para determinar como los efectos del resveratrol son mediados por AMPK. Los investigadores concluyen que AMPK es la Diana central del resveratrol
