Serum Visfatin Is Differentially Regulated by Insulin and Free Fatty Acids in Healthy Men

CONTEXT: Serum visfatin is elevated in insulin-resistant states, ie, obesity, type 2 diabetes mellitus, and polycystic ovary syndrome, thus linking visfatin with the pathogenesis of insulin resistance. OBJECTIVE: Our objective was to evaluate the effect of hyperinsulinemia and the acute elevation of free fatty acids (FFAs) on serum visfatin in humans. DESIGN, SETTING AND SUBJECTS: We estimated serum visfatin during hyperinsulinemia and the insulin-resistant conditions caused by an acute elevation of FFAs in 19 healthy male volunteers (mean age, 25 ± 7 years; body mass index, 26 ± 4 kg/m(2)) at a university hospital. INTERVENTIONS: Intervention included a 6-hour euglycemic-hyperinsulinemic clamp without and with Intralipid/heparin infusion. MAIN OUTCOME MEASURES: Measurements were made of serum visfatin at baseline and at 2 and 6 hours during both clamp studies. RESULTS: Hyperinsulinemia resulted in a significant decrease in serum visfatin concentration (P = .043). Concomitant Intralipid/heparin infusion, which caused a reduction of insulin sensitivity by 40% (P < .0001), resulted in a marked increase in serum visfatin (P < .0001), which was already observed after 2 hours of FFAs increase (P < .0001). Serum visfatin during the clamp study after 2 and 6 hours of Intralipid/heparin infusion was significantly higher than respective values during the clamp study without the elevation of FFAs (both P < .0001). The increase in serum visfatin during Intralipid/heparin infusion was positively related to body weight (r = 0.54, P = .016) and γ-glutamyltransferase activity (r = 0.56, P = .011). CONCLUSIONS: Serum visfatin is differentially regulated by insulin and FFAs. One might hypothesize that the induction of insulin resistance by FFAs suppresses insulin inhibition of visfatin secretion, resulting in a serum visfatin increase in insulin-resistant conditions.