| First Author | Lee JH | Year | 2012 |
| Journal | Cell Metab | Volume | 16 |
| Issue | 3 | Pages | 311-21 |
| PubMed ID | 22958918 | Mgi Jnum | J:189021 |
| Mgi Id | MGI:5444071 | Doi | 10.1016/j.cmet.2012.08.004 |
| Citation | Lee JH, et al. (2012) Maintenance of metabolic homeostasis by Sestrin2 and Sestrin3. Cell Metab 16(3):311-21 |
| abstractText | 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. |
