Improved Insulin Sensitivity by Bezafibrate in Rats: Relationship to Fatty Acid Composition of Skeletal-Muscle Triglycerides

Abstract

We investigated the effect of the lipid-lowering agent, bezafibrate, on insulin sensitivity in a dietary model of insulin resistance. Male Sprague-Dawley rats were divided into four groups: control group, administered a standard diet; high-fructose group, given a 40% fructose diet; high-fructose plus lard group, given a 40% fructose diet with 7% lard; and bezafibrate group, given a 40% fructose plus 7% lard diet with 10 mg · kg−1 · day−1 of oral bezafibrate. Insulin action was assessed after 2 weeks with a steady-state plasma glucose (SSPG) level. The fatty acid (FA) composition of skeletal-muscle triglycerides was also determined. A higher SSPG level (20.9 ± 0.9 vs. 16.5 ±1.1 mmol/l in the control group, P < 0.05) as well as a higher systolic blood pressure (120 ± 2 vs. 101 ± 2 mmHg, P < 0.01) was observed in the high-fructose plus lard group, but not in the high-fructose group. These changes were prevented by bezafibrate administration. The FA composition of skeletal-muscle triglycerides demonstrated a higher percentage of saturated and monounsaturated FAs (P < 0.01) and a lower percentage of polyunsaturated FAs (P < 0.01) in the highfructose plus lard group versus the control group. These changes were consistent with differences in the dietary intake of FAs. Bezafibrate virtually normalized the FA composition in the high-fructose plus lard group. The ratio of C20:4 to C20:3, an index of ∆5 desaturase activity, was significantly higher in the bezafibrate group versus the high-fructose plus lard group (8.60 ± 0.76 vs. 2.04 ± 0.27, P < 0.01). In conclusion, the dietary FA composition was closely related to insulin resistance in rats fed 40% fructose. Bezafibrate increased ∆5 desaturase activity. Such action may contribute to the improvement of insulin sensitivity.