High-fat- and lipid-induced insulin resistance in rats: The comparison of glucose metabolism, plasma resistin and adiponectin levels

Aims: In animal models, both an acute elevation in plasma free fatty acid (FFA) via intravenous infusion of a lipid emulsion and a chronic elevation in plasma FFA via high-fat feeding have been shown to induce skeletal muscle and liver insulin resistance. However, there have been very few studies comparing the effects of high-fat- and lipid-induced insulin resistance on glucose metabolism and adipocytokines. Methods: In the current study, we used lipid infusion and a high-fat feed in combination with the hyperinsulinemic-euglycemic clamp technique to assess the impact of acute and chronically elevated FFA levels on overall glucose metabolism and insulin action; two adipocytokines, resistin and adiponectin, were used. Results: At baseline, plasma FFA levels were significantly increased in the high-fat diet (HF) group compared to the control group (p < 0.05). During clamp steady-state, the FFA levels were reduced by similar to 25% in the control and similar to 48% in the HF groups. In contrast, there was a significant increase in the plasma FFA level in the lipid-infused group (from 0.82 +/- 0.03 to 2.87 +/- 0.18 mmol/l). The glucose infusion rates (GIRs) in the HF and lipid groups were obviously lower than in the control group (p < 0.01). Moreover, GIR was lower in the lipid group compared with the HF group (p < 0.05). The rate of glucose disappearance (G(Rd)) was significantly lower in the lipid group compared with the control group. Hepatic glucose production in the control group was suppressed by similar to 15% compared with the HF and lipid groups where it was suppressed by only similar to 72 and similar to 91%, respectively. The resistin level of muscle tissues in the lipid group was significantly higher compared with the control and HF groups (both p < 0.05). After the insulin clamp, the circulating adiponectin level was significantly decreased in the lipid group compared with the control and HF groups (p < 0.05). Conclusions: Lipid infusion, which was more effective than a high-fat diet, can induce peripheral and hepatic insulin resistance in rats. Insulin-induced resistance might be associated with elevated resistin and decreased adiponectin. Copyright (c) 2006 S. Karger AG, Basel.