Research Paper Volume 1, Issue 9 pp 771—783
Diet and exercise signals regulate SIRT3 and activate AMPK and PGC-1α in skeletal muscle
- 1 USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
- 2 Howard Hughes Medical Institute & Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
- 3 Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA
- 4 Department of Society, Human Development, and Health, Harvard School of Public Health, Boston, MA 02115, USA
- 5 Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
- 6 Joslin Diabetes Center & Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
- 7 These authors contributed equally to this work
Received: June 4, 2009 Accepted: August 13, 2009 Published: August 15, 2009
https://doi.org/10.18632/aging.100075How to Cite
Abstract
SIRT3 is a member of the sirtuin family of NAD+-dependent deacetylases, which is localized to the mitochondria and is enriched in kidney, brown adipose tissue, heart, and other metabolically active tissues. We report here that SIRT3 responds dynamically to both exercise and nutritional signals in skeletal muscle to coordinate downstream molecular responses. We show that exercise training increases SIRT3 expression as well as associated CREB phosphorylation and PGC-1α up-regulation. Furthermore, we show that SIRT3 is more highly expressed in slow oxidative type I soleus muscle compared to fast type II extensor digitorum longus or gastrocnemius muscles. Additionally, we find that SIRT3 protein levels in skeletal muscle are sensitive to diet, for SIRT3 expression increases by fasting and caloric restriction, yet it is decreased by high-fat diet. Interestingly, the caloric restriction regimen also leads to phospho-activation of AMPK in muscle. Conversely in SIRT3 knockout mice, we find that the phosphorylation of both AMPK and CREB and the expression of PGC-1α are down regulated, suggesting that these key cellular factors may be important components of SIRT3-mediated biological signals in vivo.