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United States Department of Agriculture

Agricultural Research Service


Location: Children's Nutrition Research Center

Title: SIRTI deficiency in mice impairs energy balance by disrupting hypothalamic melanocortin signaling)

item Shi, Xuemei
item Wang, Yi
item Li, Xiaojie
item Li, Defa
item Burrin, Douglas
item Chan, Lawrence
item Guan, Xinfu

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.

Last Modified: 05/28/2017
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