Circulating Adipocyte Fatty Acid-Binding Protein Induces Insulin Resistance in Mice In Vivo

ObjectiveCirculating 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. MethodsC57BL/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 -cell responsiveness, hepatic glycogen content, and peroxisome proliferator-activated receptor (PPAR) protein expression was elucidated. ResultsIn 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 PPAR protein content in perigonadal adipose tissue and diminished circulating adiponectin. AFABP treatment did not affect pancreatic -cell responsiveness and hepatic glycogen content. ConclusionsCirculating AFABP induces insulin resistance in male mice. AFABP-mediated degradation of PPAR in adipose tissue and subsequently decreased expression of insulin-sensitizing adiponectin are potential mechanisms for this effect.