 Recently, it is hypothesized that liver may regulate systemic energy metabolism through production of secretory proteins known as hepatokines. Fetuin-A, a circulating glycoprotein almost exclusively secreted by the liver, has been found to inhibit insulin receptor tyrosine kinase activity in animal studies 4. Fetuin-A knockout KO mice have enhanced glucose sensitivity, resistance to weight gain, and lower serum free fatty acid levels 5. In humans, high fetuin-A levels are associated with insulin resistance and fat accumulation in the liver 6. Ix et al. reported that higher human fetuin-A concentrations are strongly associated with metabolic syndrome and atherogenic lipid profile in non-diabetic patients with coronary artery disease 7. In addition, fetuin-A levels were associated with surrogate marker of atherosclerosis such as arterial stiffness and intima-media thickness IMT 8. Recent studies reported that elevated fetuin-A levels predict increased risk of myocardial infarction and ischemic stroke 9 as well as type 2 diabetes 10. However, there has been no previous report about the effects of CR on fetuin-A comparing with changes of cardiovascular risk indicators in animals or humans. 