Effects of free fatty acids on plasma resistin and insulin resistance in awake rats

Resistin has been postulated to play a role in obesity-related insulin resistance. To explore this possibility, we have investigated effects of acute euglycemic (5.2 ± 0.1 mmol/L) hyperinsulinemia (96 ± 8 μU/mL) with and without concurrent infusion of lipid plus heparin (to raise or lower plasma free fatty acid [FFA] levels) on glucose turnover and plasma resistin levels in alert rats. Plasma FFA concentrations increased during lipid/heparin (L/H) infusion (from 0.82 to 2.86 mmol/L, P < .001) and decreased (from 0.83 to 0.21 mmol/L, P < .001) in controls who were infused with insulin but not with L/H. L/H infusion reduced insulin suppression of endogenous glucose production by ∼90% (from 28.9 to 3.1 mg· kg−1 · min−1, P < .001) and insulin-stimulated glucose uptake (glucose rate of disappearance) by 78% (from 30.8% to 6.9%, P < .001). Plasma resistin levels increased by 46% (from 39.9 to 58.4 μg/L, P < .05) during L/H infusion and did not change in controls (39.7 vs 39.3 μg/L). Plasma ghrelin levels decreased by 41% (from 892 to 584 ng/L, P < .05) in response to hyperinsulinemia, whereas concurrent L/H infusion had no additional effect on ghrelin levels (584 ± 67 vs 548 ± 82 ng/L). In summary, we found that FFA induced hepatic insulin resistance, and to a lesser extent, peripheral insulin resistance was associated with elevated plasma resistin levels. We conclude that FFA-induced release of resistin may contribute to the development of FFA-induced insulin resistance in rats.