title: FABP4 is secreted from adipocytes by adenyl cyclase-PKA- and guanylyl cyclase-PKG-dependent lipolytic mechanisms.
abstract: OBJECTIVE
  Fatty acid-binding protein 4 (FABP4) is expressed in adipocytes, and elevated plasma FABP4 level is associated with obesity-mediated metabolic phenotype. Postprandial regulation and secretory signaling of FABP4 has been investigated.
  
  
  METHODS
  Time courses of FABP4 levels were examined during an oral glucose tolerance test (OGTT; n=53) or a high-fat test meal eating (n=35). Effects of activators and inhibitors of adenyl cyclase (AC)-protein kinase A (PKA) signaling and guanylyl cyclase (GC)-protein kinase G (PKG) signaling on FABP4 secretion from mouse 3T3-L1 adipocytes were investigated.
  
  
  RESULTS
  FABP4 level significantly declined after the OGTT or a high-fat meal eating, while insulin level was increased. Treatment with low and high glucose concentration or palmitate for 2 h did not affect FABP4 secretion from 3T3-L1 adipocytes. FABP4 secretion was increased by stimulation of lipolysis using isoproterenol, a β3 -adrenoceptor agonist (CL316243), forskolin, dibutyryl-cAMP and atrial natriuretic peptide, and the induced FABP4 secretion was suppressed by insulin or an inhibitor of PKA (H-89), PKG (KT5823) or hormone sensitive lipase (CAY10499).
  
  
  CONCLUSIONS
  FABP4 is secreted from adipocytes in association with lipolysis regulated by AC-PKA- and GC-PKG-mediated signal pathways. Plasma FABP4 level declines postprandially, and suppression of FABP4 secretion by insulin-induced anti-lipolytic signaling may be involved in this decline in FABP4 level.
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, 060-8543, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Mita
authors.forename: Masato
authors.initials: M
authors.lastname: Furuhashi
authors.forename: Shinya
authors.initials: S
authors.lastname: Hiramitsu
authors.forename: Junnichi
authors.initials: J
authors.lastname: Ishii
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hoshina
authors.forename: Shutaro
authors.initials: S
authors.lastname: Ishimura
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fuseya
authors.forename: Yuki
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Marenao
authors.initials: M
authors.lastname: Tanaka
authors.forename: Kohei
authors.initials: K
authors.lastname: Ohno
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Akasaka
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ohnishi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yoshida
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Saitoh
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Shimamoto
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Miura
mesh_terms: D041721:3T3-L1 Cells; D000262:Adenylyl Cyclases / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D059305:Diet, High-Fat; D050556:Fatty Acid-Binding Proteins / Q000097:blood / Q000378:metabolism*; D005260:Female; D005951:Glucose Tolerance Test; D006162:Guanylate Cyclase / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050356:Lipid Metabolism; D008066:Lipolysis; D008297:Male; D051379:Mice; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D007328:Insulin; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase