Submitted on June 21, 2008
Revised on September 18, 2008
Accepted on November 20, 2008
Fenofibrate Reduces Serum Retinol Binding Protein 4 by Suppressing its Expression in Adipose Tissue
Haiya Wu1, Li Wei1, Yunqian Bao1, Junxi Lu1, Ping Huang2, Yong Liu2, Weiping Jia1*, and Kunsan Xiang1
1 Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai Clinical Center of Diabetes
2 Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
* To whom correspondence should be addressed. E-mail: wpjia{at}sjtu.edu.cn.
Fenofibrate is a peroxisome proliferator-activated receptor 
(PPAR) activator that has been clinically used to treat dyslipidemia and insulin resistance. To better understand the molecular mechanisms underlying fenofibrate action, we investigated whether fenofibrate affects serum levels of retinol binding protein 4 (RBP4), an adipocytokine which has recently been shown to link obesity and insulin resistance. Fenofibrate treatment significantly decreased serum RBP4 levels of dyslipidemic patients, which correlated with reduced body weight and increased insulin sensitivity. To elucidate the biochemical mechanisms of fenofibrate action, we investigated the effect of fenofibrate on RBP4 expression in obese rats. Fenofibrate greatly decreased RBP4 mRNA levels in adipose tissue but not in the liver, which correlated with decreased serum RBP4 levels and increased insulin sensitivity in the obese rats. Consistent with a direct effect on RBP4 expression, fenofibrate treatment significantly reduced the mRNA expression levels of RPB4 in 3T3-L1 adipocytes. Taken together, our results demonstrate for the first time that fenobibrate inhibits RPB4 expression in dyslipidemic human subjects and suggest that inhibiting RBP4 expression in adipocytes may provide a mechanism by which fenofibrate improves insulin sensitivity in dyslipidemic patients.
