Rho-kinase Regulates Energy Balance by Targeting Hypothalamic Leptin Receptor Signaling

View/ Open
Author
Byun, Kyung Hee
Ye, Chianping
Koda, Shuichi
Lee, Dae Ho
Oh, Byung-Chul
Lee, Bonghee
Kim, Min Seon
Bjørbæk, Christian
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1038/nn.3207Metadata
Show full item recordCitation
Huang, Hu, Dong Kong, Kyung Hee Byun, Chianping Ye, Shuichi Koda, Dae Ho Lee, Byung-Chul Oh, et al. 2012. Rho-kinase regulates energy balance by targeting hypothalamic leptin receptor signaling. Nature neuroscience 15(10): 1391-1398.Abstract
Leptin regulates energy balance. However, knowledge of the critical intracellular transducers of leptin signaling remains incomplete. Here we report that Rho-kinase 1 (ROCK1) regulates leptin action on body weight homeostasis by activating JAK2, an initial trigger of leptin receptor signaling. Leptin promotes the physical interaction of JAK2 and ROCK1, thereby increasing phosphorylation of JAK2 and downstream activation of Stat3 and FOXO1. Mice lacking ROCK1 in either POMC or AgRP neurons, mediators of leptin action, display obesity and impaired leptin sensitivity. In addition, deletion of ROCK1 in the arcuate nucleus markedly enhances food intake, resulting in severe obesity. Of note, ROCK1 is a specific mediator of leptin, but not insulin, regulation of POMC neuronal activity. Our data identify ROCK1 as a key regulator of leptin action on energy homeostasis.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3458121/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:11180389
Collections
- HMS Scholarly Articles [17714]
Contact administrator regarding this item (to report mistakes or request changes)