Xbp1s in Pomc Neurons Connects ER Stress with Energy Balance and Glucose Homeostasis

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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-opio-melanocortin (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.
Publisher
CELL PRESS
Issue Date
2014-09
Language
English
Article Type
Article
Keywords

ENDOPLASMIC-RETICULUM STRESS; TYROSINE-PHOSPHATASE 1B; DIET-INDUCED OBESITY; BROWN ADIPOSE-TISSUE; ARCUATE PROOPIOMELANOCORTIN NEURONS; LIVER-SPECIFIC DELETION; NERVOUS-SYSTEM CONTROL; LEPTIN RESISTANCE; INSULIN-RESISTANCE; LINKING OBESITY

Citation

CELL METABOLISM, v.20, no.3, pp.471 - 482

ISSN
1550-4131
DOI
10.1016/j.cmet.2014.06.002
URI
http://hdl.handle.net/10203/194523
Appears in Collection
BS-Journal Papers(저널논문)
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