Rho-kinase Regulates Energy Balance by Targeting Hypothalamic Leptin Receptor Signaling
Byun, Kyung Hee
Lee, Dae Ho
Kim, Min Seon
MetadataShow full item record
CitationHuang, 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.
AbstractLeptin 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.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11180389
- HMS Scholarly Articles