@article{d92c31f639844429be05b14e84abe322,
title = "Xbp1s in pomc neurons connects ER stress with energy balance and glucose homeostasis",
abstract = "Summary The molecular mechanisms underlying neuronal leptin and insulin resistance in obesity and diabetes remain unclear. Here we show that induction of the unfolded protein response transcription factor spliced X-box binding protein 1 (Xbp1s) in pro-opiomelanocortin (Pomc) neurons alone is sufficient to protect against diet-induced obesity as well as improve leptin and insulin sensitivity, even in the presence of strong activators of ER stress. We also demonstrate that constitutive expression of Xbp1s in Pomc neurons contributes to improved hepatic insulin sensitivity and suppression of endogenous glucose production. Notably, elevated Xbp1s levels in Pomc neurons also resulted in activation of the Xbp1s axis in the liver via a cell-nonautonomous mechanism. Together our results identify critical molecular mechanisms linking ER stress in arcuate Pomc neurons to acute leptin and insulin resistance as well as liver metabolism in diet-induced obesity and diabetes.",
author = "Williams, {Kevin W.} and Tiemin Liu and Xingxing Kong and Makoto Fukuda and Yingfeng Deng and Berglund, {Eric D.} and Zhuo Deng and Yong Gao and Tianya Liu and Sohn, {Jong Woo} and Lin Jia and Teppei Fujikawa and Daisuke Kohno and Scott, {Michael M.} and Syann Lee and Lee, {Charlotte E.} and Kai Sun and Yongsheng Chang and Scherer, {Philipp E.} and Elmquist, {Joel K.}",
note = "Funding Information: We thank Dr. Jeffrey Friedman (Rockefeller University) for kindly providing us with the Lepr-cre mice. We also thank Dr. Bradford Lowell (Beth Israel Deaconess Medical Center) for kindly providing us with the Pomc-hrGFP mice. This work was supported by grants to K.W.W. (K01DK087780), Tiemin Liu (American Diabetes Association 7-11-MN-16), M.F. (American Heart Association 9SDG2080223), J.-W.S. (American Heart Association 12POST8860007), Y.D. (American Diabetes Association 7-08-MN-53), E.D.B. (NIH F32 DK092083 and K01 DK098317), X.K. (American Heart Association 13POST16710016), T.F. (Juvenile Diabetes Research Foundation 3-2011-405), and J.K.E. (R01DK53301, R01DK088423, and RL1DK081185). This work was also supported by PL1 DK081182 and UL1RR024923, as well as P01DK088761 (P.E.S. and J.K.E.) and R01DK55758 (P.E.S.). ",
year = "2014",
month = sep,
day = "2",
doi = "10.1016/j.cmet.2014.06.002",
language = "English (US)",
volume = "20",
pages = "471--482",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "3",
}