Experimental hyperlipidemia induces insulin resistance in sheep

This study aimed to evaluate the effects of intravenous infusion of a soybean-based lipid emulsion on some blood energy-related metabolites and insulin sensitivity indexes in sheep. Four clinically healthy ewes were assigned into a 2-treatment, 2-period cross-over design. Either normal saline (NS) or lipid emulsion (LE) was intravenously introduced at a rate of 0.025 mL·kg(-1) min(-1) for 6 h. The concentrations of blood nonesterified fatty acid (NEFA), beta-hydroxybutyrate, triglyceride, cholesterol, urea, creatinine, cortisol, glucose, and insulin were measured at different time points. After 6 h, intravenous glucose tolerance test was performed. Lipid infusion elicited an increase (P < 0.05) in the NEFA, beta-hydroxybutyrate, and triglyceride concentrations compared with the baseline value and NS infusion. Infusion of NS did not influence blood glucose concentration; however, LE infusion increased plasma glucose concentration (P < 0.05). At time point 12 h, serum insulin concentrations were increased (P < 0.05) in NS treatment; however, such an increase was not observed in the LE treatment. Insulin sensitivity index for the LE infusion was lower (P < 0.05) than that for the NS treatment. The glucose effectiveness was not (P > 0.05) different among treatments. In the LE treatment, acute-phase insulin responses increased (P < 0.05) and disposition index decreased (P < 0.001) compared with NS treatment. The results showed that experimentally induced NEFA in blood could cause insulin resistance in sheep. The current model could be used to evaluate the pathogenesis of conditions associated with increased lipid mobilization and insulin resistance.