Circulating Angptl8 is positively and independently associated with T2DM and fasting glucose in vivo. Furthermore, Angptl8 mRNA expression is induced by insulin and during adipogenesis in 3T3-L1 adipocytes in vitro.
Leptin administration within the subphysiological to physiological range diminishes atherosclerotic lesions. Leptin appears to mediate its antiatherogenic effects indirectly through reduction of hypercholesterolemia and liver steatosis, as well as upregulation of insulin-sensitizing and atheroprotective adiponectin.
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.
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