title: Effects of peroxisome proliferator-activated receptor ligands, bezafibrate and fenofibrate, on adiponectin level.
abstract: OBJECTIVE
  Adiponectin is adipose-specific secretory protein and acts as anti-diabetic and anti-atherosclerotic molecule. We previously found peroxisome proliferators response element in adiponectin promoter region, suggesting that peroxisome proliferator-activated receptor (PPAR) ligands elevate adiponectin. Fibrates are known to be PPARalpha ligands and were shown to reduce risks of diabetes and cardiovascular disease. Effect of fibrates on adiponectin has not been clarified, whereas thiazolidinediones enhance adiponectin. Thus, we explored the possibility and mechanism that fibrates enhance adiponectin in humans, mice, and cells.
  
  
  RESULTS
  Significant increase of serum adiponectin was observed in bezafibrate-treated subjects compared with placebo group in patients enrolled in The Bezafibrate Infarction Prevention study. Higher baseline adiponectin levels were strongly associated with reduced risk of new diabetes. Fibrates, bezafibrate and fenofibrate, significantly elevated adiponectin levels in wild-type mice and 3T3-L1 adipocytes. Such an effect was not observed in PPARalpha-deficient mice and adipocytes. Fibrates activated adiponectin promoter but failed to enhance its activity when the point mutation occurred in peroxisome proliferators response element site and the endogenous PPARalpha was knocked down by PPARalpha-RNAi.
  
  
  CONCLUSIONS
  Our results suggest that fibrates enhance adiponectin partly through adipose PPARalpha and measurement of adiponectin might be a useful tool for searching subjects at high risk for diabetes.
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2, B5, Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Hiuge
authors.forename: Alexander
authors.initials: A
authors.lastname: Tenenbaum
authors.forename: Norikazu
authors.initials: N
authors.lastname: Maeda
authors.forename: Michal
authors.initials: M
authors.lastname: Benderly
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kumada
authors.forename: Enrique Z
authors.initials: EZ
authors.lastname: Fisman
authors.forename: David
authors.initials: D
authors.lastname: Tanne
authors.forename: Zipora
authors.initials: Z
authors.lastname: Matas
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Hibuse
authors.forename: Koichi
authors.initials: K
authors.lastname: Fujita
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nishizawa
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Adler
authors.forename: Michael
authors.initials: M
authors.lastname: Motro
authors.forename: Shinji
authors.initials: S
authors.lastname: Kihara
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
authors.forename: Solomon
authors.initials: S
authors.lastname: Behar
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism*; D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D001629:Bezafibrate / Q000627:therapeutic use*; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004311:Double-Blind Method; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D005786:Gene Expression Regulation; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008024:Ligands; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism*; D011336:Probability; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis; D018709:Statistics, Nonparametric; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism
chemical_list: D052242:Adiponectin; D000960:Hypolipidemic Agents; D008024:Ligands; D047492:Peroxisome Proliferator-Activated Receptors; D012333:RNA, Messenger; D011345:Fenofibrate; D001629:Bezafibrate