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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| Published in: | Cell metabolism Vol. 15; no. 5; p. 675 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
02.05.2012
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| Subjects: | |
| ISSN: | 1932-7420, 1932-7420 |
| Online Access: | Get more information |
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| 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. |
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| AbstractList | 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. 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.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. |
| Author | North, Brian J Agarwal, Beamon Price, Nathan L Varamini, Behzad Duarte, Filipe V Ye, Lan Hubbard, Basil P Hafner, Angela Teodoro, Joao S Sinclair, David A Varela, Ana T Ling, Alvin J Y Palmeira, Carlos M Gomes, Ana P Davis, James G Baur, Joseph A Coppari, Roberto de Cabo, Rafael Moaddel, Ruin Martin-Montalvo, Alejandro Ramadori, Giorgio Rolo, Anabela P |
| Author_xml | – sequence: 1 givenname: Nathan L surname: Price fullname: Price, Nathan L organization: Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, Boston, MA 02115, USA – sequence: 2 givenname: Ana P surname: Gomes fullname: Gomes, Ana P – sequence: 3 givenname: Alvin J Y surname: Ling fullname: Ling, Alvin J Y – sequence: 4 givenname: Filipe V surname: Duarte fullname: Duarte, Filipe V – sequence: 5 givenname: Alejandro surname: Martin-Montalvo fullname: Martin-Montalvo, Alejandro – sequence: 6 givenname: Brian J surname: North fullname: North, Brian J – sequence: 7 givenname: Beamon surname: Agarwal fullname: Agarwal, Beamon – sequence: 8 givenname: Lan surname: Ye fullname: Ye, Lan – sequence: 9 givenname: Giorgio surname: Ramadori fullname: Ramadori, Giorgio – sequence: 10 givenname: Joao S surname: Teodoro fullname: Teodoro, Joao S – sequence: 11 givenname: Basil P surname: Hubbard fullname: Hubbard, Basil P – sequence: 12 givenname: Ana T surname: Varela fullname: Varela, Ana T – sequence: 13 givenname: James G surname: Davis fullname: Davis, James G – sequence: 14 givenname: Behzad surname: Varamini fullname: Varamini, Behzad – sequence: 15 givenname: Angela surname: Hafner fullname: Hafner, Angela – sequence: 16 givenname: Ruin surname: Moaddel fullname: Moaddel, Ruin – sequence: 17 givenname: Anabela P surname: Rolo fullname: Rolo, Anabela P – sequence: 18 givenname: Roberto surname: Coppari fullname: Coppari, Roberto – sequence: 19 givenname: Carlos M surname: Palmeira fullname: Palmeira, Carlos M – sequence: 20 givenname: Rafael surname: de Cabo fullname: de Cabo, Rafael – sequence: 21 givenname: Joseph A surname: Baur fullname: Baur, Joseph A – sequence: 22 givenname: David A surname: Sinclair fullname: Sinclair, David A |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/22560220$$D View this record in MEDLINE/PubMed |
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| Title | SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function |
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