Fenofibrate reduces serum retinol-binding protein-4 by suppressing its expression in adipose tissue.
Fenofibrate is a peroxisome proliferator-activated receptor-alpha (PPARalpha) 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 that 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 obese rats. Consistent with a direct effect on RBP4 expression, fenofibrate treatment significantly reduced the mRNA expression levels of RPB4 in 3T3-L1 adipocytes. Together, our results demonstrate for the first time that fenofibrate inhibits RPB4 expression in dyslipidemic human subjects and suggest that inhibition of RBP4 expression in adipocytes may provide a mechanism by which fenofibrate improves insulin sensitivity in dyslipidemic patients.
Wu
Haiya
H
Department of Endocrinology and Metabolism, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai Clinical Center of Diabetes, 600 Yishan Rd., Shanghai 200233, China.
Wei
Li
L
Bao
Yuqian
Y
Lu
Junxi
J
Huang
Ping
P
Liu
Yong
Y
Jia
Weiping
W
Xiang
Kunsan
K
D041721:3T3-L1 Cells; D052242:Adiponectin / Q000097:blood / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000328:Adult; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D050171:Dyslipidemias / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D011345:Fenofibrate / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D054839:Retinol-Binding Proteins, Plasma / Q000235:genetics* / Q000378:metabolism
C499918:ADIPOQ protein, human; D052242:Adiponectin; D000960:Hypolipidemic Agents; C101326:RBP4 protein, human; D054839:Retinol-Binding Proteins, Plasma; D011345:Fenofibrate