Circulating adipocyte fatty acid-binding protein induces insulin resistance in micein 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 b-cell responsiveness, hepatic glycogen content, and peroxisome proliferator-activated receptor (PPAR) c 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 PPARc protein content in perigonadal adipose tissue and diminished circulating adiponectin. AFABP treatment did not affect pancreatic b-cell responsiveness and hepatic glycogen content. Conclusions: Circulating AFABP induces insulin resistance in male mice. AFABP-mediated degradation of PPARc in adipose tissue and subsequently decreased expression of insulin-sensitizing adiponectin are potential mechanisms for this effect.

Metabolic functions of FABPs—mechanisms and therapeutic implications

“…Furthermore, reduced insulin secretion in the setting of adrenergic stimulation has been previously described in FABP4-deficient mice, which was attributed to alteration of free fatty acid profile. 64 Indeed, delivery of exogenous FABP4 can induce insulin resistance without altering β cell responsiveness, 150 consequently FABP4 might initiate hyperinsulinaemia downstream of insulin resistance.…”

Cytokine-like Activity of Liver Type Fatty Acid Binding Protein (L-FABP) Inducing Inflammatory Cytokine Interleukin-6

“…Furthermore, another study revealed that exogenous A-FABP can induce replication and migration of human coronary artery smooth muscle cells (33). Moreover, some recent studies reported that exogenous A-FABP to primary hepatocytes can induce gluconeogenesis (19), and insulin resistance without altering beta-cell responsiveness in the pancreas (20). Altogether, previous data suggest that A-FABP has some hormonal functions on other tissues after release from adipose tissue.…”

“…L-FABP is detectable in bile in the absence of cellular injury (), H-, A-, and E-FABPs are present in milk (1415), and several recent reports have shown that A-FABP is secreted from adipocytes into the circulation or extracellular spaces (1617). Furthermore, it has become evident that the A-FABP after release from adipose tissue has crucial hormonal functions on liver, pancreas and heart (181920). As for the role of L-FABP, different studies have shown that urinary L-FABP in humans would be a useful clinical marker for acute kidney injury, and prediction and monitoring of the progression of chronic kidney disease (212223).…”

Circulating serum chemerin levels are elevated in lipodystrophy

“…Chemerin (Chem) mRNA synthesis was determined relative to 36B4 by quantitative real-time RT-PCR in a fluorescent temperature cycler (Roche, Heidelberg, Germany) as described previously 29 using the following mouse primers: Chem:…”