title: Circulating adipocyte fatty acid-binding protein induces insulin resistance in mice in vivo.
abstract: OBJECTIVE
  Circulating levels of the adipokine adipocyte fatty acid-binding protein (AFABP) are increased in obesity. However, the influence of circulating AFABP on insulin sensitivity in vivo remains unclear.
  
  
  METHODS
  C57BL/6NTac mice (10 weeks) were treated over 8 weeks i.p. with saline (control) or recombinant AFABP (0.5 mg/kg/d). A comprehensive characterization of metabolic parameters, body composition, and energy expenditure was performed. Furthermore, the effect of AFABP on pancreatic β-cell responsiveness, hepatic glycogen content, and peroxisome proliferator-activated receptor (PPAR) γ protein expression was elucidated.
  
  
  RESULTS
  In male mice, AFABP treatment induced insulin resistance with significantly increased fasting insulin, C-peptide, and homeostasis model assessment of insulin resistance. In female animals, a similar trend was observed. In both genders, no difference in body weight, lipid parameters, body composition, or energy expenditure could be detected between AFABP-treated and control mice. Insulin resistance in male AFABP-treated mice was accompanied by decreased PPARγ protein content in perigonadal adipose tissue and diminished circulating adiponectin. AFABP treatment did not affect pancreatic β-cell responsiveness and hepatic glycogen content.
  
  
  CONCLUSIONS
  Circulating AFABP induces insulin resistance in male mice. AFABP-mediated degradation of PPARγ in adipose tissue and subsequently decreased expression of insulin-sensitizing adiponectin are potential mechanisms for this effect.
authors: Department of Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany; Leipzig University Medical Center, IFB AdiposityDiseases, Leipzig, Germany.
authors: Susan
authors: S
authors: Kralisch
authors: Nora
authors: N
authors: Klöting
authors: Thomas
authors: T
authors: Ebert
authors: Matthias
authors: M
authors: Kern
authors: Annett
authors: A
authors: Hoffmann
authors: Kerstin
authors: K
authors: Krause
authors: Beate
authors: B
authors: Jessnitzer
authors: Ulrike
authors: U
authors: Lossner
authors: Ines
authors: I
authors: Sommerer
authors: Michael
authors: M
authors: Stumvoll
authors: Mathias
authors: M
authors: Fasshauer
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D052242:Adiponectin / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D002096:C-Peptide / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism
chemical_list: D052242:Adiponectin; D002096:C-Peptide; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D007328:Insulin; D047495:PPAR gamma