Metabolic actions of Rho-kinase in periphery and brain

• ROCK inhibition is beneficial for cardiovascular-related diseases.
• ROCK positively regulates metabolic action of insulin on glucose transport.
• Loss of ROCK1 in hypothalamic neurons of mice promotes adiposity.
• ROCK1 regulates energy balance by targeting hypothalamic leptin receptor signaling.

Obesity has increased at an alarming rate in recent years and is now a worldwide public health problem. Elucidating the mechanisms behind the metabolic dysfunctions associated with obesity is of high priority. The metabolic function of Rho-kinase (Rho-associated coiled-coil-containing kinase; ROCK) has been the subject of a great deal of investigation in metabolic-related diseases. It appears that inhibition of ROCK activity is beneficial for the treatment of a wide range of cardiovascular-related diseases. However, recent studies with genetic models of ROCK demonstrate that ROCK plays a positive role in insulin and leptin signaling. Here we discuss the newly identified functions of ROCK in regulating glucose and energy metabolism, with particular emphasis on metabolic actions of insulin and leptin.