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Citation
Lee, J.H., Budanov, A.V., Talukdar, S., Park, E.J., Park, H.L., Park, H.W., Bandyopadhyay, G., Li, N., Aghajan, M., Jang, I., Wolfe, A.M., Perkins, G.A., Ellisman, M.H., Bier, E., Scadeng, M., Foretz, M., Viollet, B., Olefsky, J., Karin, M. (2012). Maintenance of metabolic homeostasis by Sestrin2 and Sestrin3.  Cell Metab. 16(3): 311--321.
FlyBase ID
FBrf0244812
Publication Type
Research paper
Abstract

Chronic activation of mammalian target of rapamycin complex 1 (mTORC1) and p70 S6 kinase (S6K) in response to hypernutrition contributes to obesity-associated metabolic pathologies, including hepatosteatosis and insulin resistance. Sestrins are stress-inducible proteins that activate AMP-activated protein kinase (AMPK) and suppress mTORC1-S6K activity, but their role in mammalian physiology and metabolism has not been investigated. We show that Sestrin2--encoded by the Sesn2 locus, whose expression is induced upon hypernutrition--maintains metabolic homeostasis in liver of obese mice. Sesn2 ablation exacerbates obesity-induced mTORC1-S6K activation, glucose intolerance, insulin resistance, and hepatosteatosis, all of which are reversed by AMPK activation. Furthermore, concomitant ablation of Sesn2 and Sesn3 provokes hepatic mTORC1-S6K activation and insulin resistance even in the absence of nutritional overload and obesity. These results demonstrate an important homeostatic function for the stress-inducible Sestrin protein family in the control of mammalian lipid and glucose metabolism.

PubMed ID
PubMed Central ID
PMC3687365 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Cell Metab.
    Title
    Cell Metabolism
    Publication Year
    2005-
    ISBN/ISSN
    1550-4131
    Data From Reference
    Alleles (6)
    Genes (6)
    Insertions (1)
    Transgenic Constructs (4)