FABP4 is secreted from adipocytes by adenyl cyclase-PKA- and guanylyl cyclase-PKG-dependent lipolytic mechanisms

Obesity (Silver Spring). 2015 Feb;23(2):359-67. doi: 10.1002/oby.20954. Epub 2014 Dec 17.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adenylyl Cyclases / metabolism*
  • Adipocytes / metabolism*
  • Adult
  • Aged
  • Animals
  • Blood Glucose / analysis
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Cyclic GMP-Dependent Protein Kinases / metabolism*
  • Diet, High-Fat
  • Fatty Acid-Binding Proteins / blood
  • Fatty Acid-Binding Proteins / metabolism*
  • Female
  • Glucose Tolerance Test
  • Guanylate Cyclase / metabolism*
  • Humans
  • Insulin / metabolism
  • Lipid Metabolism
  • Lipolysis
  • Male
  • Mice
  • Middle Aged


  • Blood Glucose
  • FABP4 protein, human
  • Fatty Acid-Binding Proteins
  • Insulin
  • Cyclic AMP-Dependent Protein Kinases
  • Cyclic GMP-Dependent Protein Kinases
  • Adenylyl Cyclases
  • Guanylate Cyclase