title: Reduction of circulating FABP4 level by treatment with omega-3 fatty acid ethyl esters.
abstract: BACKGROUND
  Fatty acid-binding protein 4 (FABP4/A-FABP/aP2) mainly expressed in adipocytes is secreted and acts as an adipokine. Increased circulating FABP4 level is associated with obesity, insulin resistance and atherosclerosis. However, little is known about the modulation of serum FABP4 level by drugs including anti-dyslipidemic agents.
  
  
  METHODS
  Patients with dyslipidemia were treated with omega-3 fatty acid ethyl esters (4 g/day; n = 14) containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for 4 weeks. Serum FABP4 level was measured before and after treatment. Expression and secretion of FABP4 were also examined in mouse 3T3-L1 adipocytes treated with EPA or DHA.
  
  
  RESULTS
  Treatment with omega-3 fatty acid ethyl esters significantly decreased triglycerides and serum FABP4 level (13.5 ± 1.5 vs. 11.5 ± 1.1 ng/ml, P = 0.017). Change in FABP4 level by omega-3 fatty acids was negatively correlated with change in levels of EPA + DHA (r = -0.643, P = 0.013), EPA (r = -0.540, P = 0.046) and DHA (r = -0.650, P = 0.011) but not change in the level of triglycerides or other fatty acid composition. Treatment of 3T3-L1 adipocytes with EPA or DHA had no effect on short-term (2 h) secretion of FABP4. However, gene expression and long-term (24 h) secretion of FABP4 were significantly reduced by treatment with EPA or DHA.
  
  
  CONCLUSIONS
  Omega-3 fatty acids decrease circulating FABP4 level, possibly by reducing expression and consecutive secretion of FABP4 in adipocytes. Reducing FABP4 level might be involved in suppression of cardiovascular events by omega-3 fatty acids.
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan. furuhasi@sapmed.ac.jp.
authors.forename: Masato
authors.initials: M
authors.lastname: Furuhashi
authors.affiliation: Hiramitsu Heart Clinic, Shiroshita-cho 2-35, Minami-ku, Nagoya, 457-0047, , Aichi, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Hiramitsu
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Mita
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Akina
authors.initials: A
authors.lastname: Omori
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fuseya
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Shutaro
authors.initials: S
authors.lastname: Ishimura
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hoshina
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Marenao
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Norihito
authors.initials: N
authors.lastname: Moniwa
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yoshida
authors.affiliation: Department of Joint Research Laboratory of Clinical Medicine, Fujita Health University School of Medicine, Toyoake, 470-1192, , Aichi, Japan.
authors.forename: Junnichi
authors.initials: J
authors.lastname: Ishii
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Miura
mesh_terms: D041721:3T3-L1 Cells; D000328:Adult; D000818:Animals; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy; D004952:Esters / Q000494:pharmacology* / Q000627:therapeutic use; D050556:Fatty Acid-Binding Proteins / Q000097:blood* / Q000235:genetics; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D051379:Mice
chemical_list: D004952:Esters; C493410:FABP4 protein, human; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D015525:Fatty Acids, Omega-3