Summary 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.

these authors contributed equally to this work.

The effect of process parameters such as plasma composition, ICP (Inductively Coupled Plasma) source power and rf chuck power on the etch characteristics of GaN epitaxy layer was studied. Cl 2 /Ar ICP discharges showed higher etch rates than SF 6 /Ar discharges because of the higher volatility of GaCl x etch products than GaF x compounds. As the Ar ratio increases in the Cl 2 /Ar ICP discharges, the etch anisotropy was enhanced due to the improved physical component of the etching. For both plasma chemistries, the GaN etch rate increased continuously as both the ICP source power and rf chuck power increased, and a maximum etch rate of 251.9 nm/min was obtained at 13Cl 2 /2Ar, 750 W ICP power, 400 W rf chuck power and 10 mTorr condition.