Circulating adipocyte fatty acid-binding protein induces insulin resistance in micein vivo
- 10 April 2015
- Vol. 23 (5), 1007-1013
- https://doi.org/10.1002/oby.21057
Abstract
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.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.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.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.Keywords
Funding Information
- Deutsche Forschungsgemeinschaft (DFG) (SFB 1052/1, C06 to M.F. and B04 to N.K.)
- Federal Ministry of Education and Research (BMBF) (FKZ: 01EO1001 (IFB AdiposityDiseases, project K7-3 to M.F., K7-58 to M.F., K05B to N.K)
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