Results
Title

Rho-kinase regulates energy balance by targeting hypothalamic leptin receptor signaling.

Authors

Huang, Hu; Kong, Dong; Byun, Kyung Hee; Ye, Chianping; Koda, Shuichi; Lee, Dae Ho; Oh, Byung-Chul; Lee, Sam W; Lee, Bonghee; Zabolotny, Janice M; Kim, Min Seon; Bjørbæk, Christian; Lowell, Bradford B; Kim, Young-Bum

Abstract

Leptin regulates energy balance. However, knowledge of the critical intracellular transducers of leptin signaling remains incomplete. We found that Rho-kinase 1 (ROCK1) regulates leptin action on body weight homeostasis by activating JAK2, an initial trigger of leptin receptor signaling. Leptin promoted the physical interaction of JAK2 and ROCK1, thereby increasing phosphorylation of JAK2 and downstream activation of Stat3 and FOXO1. Mice lacking ROCK1 in either pro-opiomelanocortin (POMC) or agouti-related protein neurons, mediators of leptin action, displayed obesity and impaired leptin sensitivity. In addition, deletion of ROCK1 in the arcuate nucleus markedly enhanced food intake, resulting in severe obesity. Notably, ROCK1 was 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.

Subjects

LEPTIN receptors; BIOENERGETICS; BODY weight; HOMEOSTASIS; PROTEIN-protein interactions; PHOSPHORYLATION; NEURONS; SENSITIVITY analysis

Publication

Nature Neuroscience, 2012, Vol 15, Issue 10, p1391

ISSN

1097-6256

Publication type

Academic Journal

DOI

10.1038/nn.3207