SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function

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 SIRT...

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Vydané v:Cell metabolism Ročník 15; číslo 5; s. 675
Hlavní autori: Price, Nathan L, Gomes, Ana P, Ling, Alvin J Y, Duarte, Filipe V, Martin-Montalvo, Alejandro, North, Brian J, Agarwal, Beamon, Ye, Lan, Ramadori, Giorgio, Teodoro, Joao S, Hubbard, Basil P, Varela, Ana T, Davis, James G, Varamini, Behzad, Hafner, Angela, Moaddel, Ruin, Rolo, Anabela P, Coppari, Roberto, Palmeira, Carlos M, de Cabo, Rafael, Baur, Joseph A, Sinclair, David A
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States 02.05.2012
Predmet:
Animals
Cells, Cultured
Enzyme Activation
Hepatocytes - drug effects
Hepatocytes - enzymology
Mice
Mice, Inbred C57BL
Mice, Knockout
Mitochondria - drug effects
Mitochondria - enzymology
Mitochondria - genetics
Muscle, Skeletal - drug effects
Muscle, Skeletal - enzymology
NAD - metabolism
Protein Kinases - genetics
Protein Kinases - metabolism
Signal Transduction - drug effects
Sirtuin 1 - genetics
Sirtuin 1 - metabolism
Stilbenes - pharmacology
ISSN:1932-7420, 1932-7420
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Popis
Shrnutí: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.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1932-7420
1932-7420
DOI:10.1016/j.cmet.2012.04.003