Author
SHI, XUEMEI - Children'S Nutrition Research Center (CNRC) | |
WANG, YI - China Agricultural University | |
LI, XIAOJIE - China Agricultural University | |
LI, DEFA - China Agricultural University | |
BURRIN, DOUGLAS - Children'S Nutrition Research Center (CNRC) | |
CHAN, LAWRENCE - Baylor College Of Medicine | |
GUAN, XINFU - Children'S Nutrition Research Center (CNRC) |
Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only Publication Acceptance Date: 1/25/2011 Publication Date: 4/1/2011 Citation: Shi, X., Wang, Y., Li, X., Li, D., Burrin, D., Chan, L., Guan, X. 2011. SIRTI deficiency in mice impairs energy balance by disrupting hypothalamic melanocortin signaling [abstract]. Federation of American Societies for Experimental Biology Conference. 25:351.1. Interpretive Summary: Technical Abstract: The NAD+-dependent deacetylase SIRT1 is induced to adjust energy metabolism in response to caloric restriction and probably mediates mammalian longevity. Due to extremely high rates of SIRT1-null neonatal mice, the physiological significance of SIRT1 has not been fully defined in whole-body energy homeostasis. Our objective was to critically test if SIRT1 deficiency impairs energy balance partially attributed to disorderly central melanocortin signaling. First, we showed that SIRT1-null mice had relatively higher food intake, augmented whole-body energy expenditure, enhanced locomotor activity, and retarded body size of the same body composition. Then, we demonstrated that the melanocortin system in the SIRT1-null mice was disrupted at the hypothalamic level. In the hypothalamus, SIRT1 protein expressed in both AgRP- and POMC-neurons and linked with AMPK-mTOR signaling. Moreover, SIRT1 protein increased at the fast status and interacted directly with FOXO1 and PGC-1 alpha in the hypothalamus. Furthermore, the relative expression of Agrp to Pomc in the SIRT1-deficient hypothalamus did not respond to energy availability. Finally, we demonstrated that SIRT1 deficiency impaired leptin-mediated AMPK and STAT3 signaling in the hypothalamus. We conclude that SIRT1 as an energy sensor positively regulates energy balance partially through hypothalamic control of whole-body energy metabolism. |