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

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

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Title: Rho-kinase Regulates Energy Balance by Targeting Hypothalamic Leptin Receptor Signaling
Author: Huang, Hu; Kong, Dong; Byun, Kyung Hee; Ye, Chianping; Koda, Shuichi; Lee, Dae Ho; Oh, Byung-Chul; Lee, Sam Whan; Lee, Bonghee; Zabolotny, Janice M.; Kim, Min Seon; Bjørbæk, Christian; Lowell, Bradford Barr; Kim, Young-Bum

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Citation: 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.
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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.
Published Version: doi:10.1038/nn.3207
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#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11180389
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