Abstract：
:Resveratrol induces mitochondrial biogenesis and protects against metabolic decline, but whether SIRT1 mediates these benefits is the subject of debate. To circumvent the developmental defects of germline SIRT1 knockouts, we have developed an inducible system that permits whole-body deletion of SIRT1 in adult mice. Mice treated with a moderate dose of resveratrol showed increased mitochondrial biogenesis and function, AMPK activation, and increased NAD(+) levels in skeletal muscle, whereas SIRT1 knockouts displayed none of these benefits. A mouse overexpressing SIRT1 mimicked these effects. A high dose of resveratrol activated AMPK in a SIRT1-independent manner, demonstrating that resveratrol dosage is a critical factor. Importantly, at both doses of resveratrol no improvements in mitochondrial function were observed in animals lacking SIRT1. Together these data indicate that SIRT1 plays an essential role in the ability of moderate doses of resveratrol to stimulate AMPK and improve mitochondrial function both in vitro and in vivo.
journal_name
Cell Metabjournal_title
Cell metabolismauthors
Price NL,Gomes AP,Ling AJ,Duarte FV,Martin-Montalvo A,North BJ,Agarwal B,Ye L,Ramadori G,Teodoro JS,Hubbard BP,Varela AT,Davis JG,Varamini B,Hafner A,Moaddel R,Rolo AP,Coppari R,Palmeira CM,de Cabo R,Baur JA,Sindoi
10.1016/j.cmet.2012.04.003subject
Has Abstractpub_date
2012-05-02 00:00:00pages
675-90issue
5eissn
1550-4131issn
1932-7420pii
S1550-4131(12)00143-Xjournal_volume
15pub_type
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