The effects of caloric restriction on fetuin-A and cardiovascular risk factors in rats and humans: a randomized controlled trial.
OBJECTIVE
The liver-secreted protein fetuin-A is associated with insulin resistance, metabolic syndrome, type 2 diabetes and atherosclerosis. We examined the effect of caloric restriction (CR) on fetuin-A levels and concomitant changes in hepatic steatosis and cardiovascular risk factors in rats and humans.


METHODS
We performed a randomized, controlled clinical trial to examine circulating fetuin-A levels and cardiovascular risk parameters including visceral fat area (VFA), atherogenic lipid profile, inflammatory markers, adipokines levels and brachial artery endothelial function in 76 overweight women with type 2 diabetes before and after 12 weeks of CR. In addition, the effects of CR on hepatic steatosis and fetuin-A mRNA expression were evaluated in Otuska Long Evans Tokushima Fatty (OLETF) rats, an animal model of obesity and type 2 diabetes.


RESULTS
Circulating fetuin-A levels were significantly decreased after 12 weeks of CR and were accompanied by improvements in VFA, blood pressure, glucose, lipid profiles and liver function. The CR group also showed a significant decrease in apolipoprotein B, leptin and insulin resistance compared to those in the control group, although endothelial function was not different. Multiple regression analysis showed that the changes in fetuin-A levels were independently associated with CR and changes in hsCRP and adiponectin (R² = 0·156). Moreover, CR significantly reduced hepatic steatosis and fetuin-A expression, as well as weight, glucose, total cholesterol and triglyceride levels, in OLETF rats.


CONCLUSIONS
Caloric restriction significantly reduced the hepatic expression of fetuin-A and its circulating levels and improved several cardiovascular risk factors in obese rats and humans with type 2 diabetes.
Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea.
Kyung Mook
KM
Choi
Kyung Ah
KA
Han
Hee Jung
HJ
Ahn
So Young
SY
Lee
Soon Young
SY
Hwang
Baek-Hui
BH
Kim
Ho Cheol
HC
Hong
Hae Yoon
HY
Choi
Sae Jeong
SJ
Yang
Hye Jin
HJ
Yoo
Sei Hyun
SH
Baik
Dong Seop
DS
Choi
Kyung Wan
KW
Min
D054392:Adipokines / Q000096:biosynthesis; D000368:Aged; D000818:Animals; D001823:Body Composition; D031204:Caloric Restriction; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D048909:Diabetes Complications / Q000175:diagnosis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D005234:Fatty Liver / Q000517:prevention & control; D005260:Female; D006801:Humans; D007249:Inflammation; D050152:Intra-Abdominal Fat / Q000473:pathology; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D050177:Overweight; D051381:Rats; D020318:Rats, Long-Evans; D012307:Risk Factors; D014057:Tomography, X-Ray Computed; D060749:alpha-2-HS-Glycoprotein / Q000096:biosynthesis*
D054392:Adipokines; D008055:Lipids; D060749:alpha-2-HS-Glycoprotein