IMPROVED INSULIN SENSITIVITY BY BEZAFIBRATE IN RATS - RELATIONSHIP TOFATTY-ACID COMPOSITION OF SKELETAL-MUSCLE TRIGLYCERIDES

We investigated the effect of the lipid-lowering agent, bezafibrate, o n insulin sensitivity in a dietary model of insulin resistance. Male S prague-Dawley rats were divided into four groups: control group, admin istered a standard diet; high-fructose group, given a 40% fructose die t; high-fructose plus lard group, given a 40% fructose diet with 7% la rd; and bezafibrate group, given a 40% fructose plus 7% lard diet with 10 mg . kg(-1) . day(-1) of oral bezafibrate. Insulin action was asse ssed after 2 weeks with a steady-state plasma glucose (SSPG) level. Th e fatty acid (FA) composition of skeletal-muscle triglycerides was als o 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 p ressure (120 +/- 2 vs. 101 +/- 2 mmHg, P < 0.01) was observed in the h igh-fructose plus lard group, but not in the high-fructose group. Thes e changes were prevented by bezafibrate administration. The FA composi tion of skeletal-muscle triglycerides demonstrated a higher percentage of saturated and monounsaturated FAs (P < 0.01) and a lower percentag e of polyunsaturated FAs (P < 0.01) in the high-fructose plus lard gro up versus the control group. These changes were consistent with differ ences in the dietary intake of FAs. Bezafibrate virtually normalized t he FA composition in the high-fructose plus lard group. The ratio of C 20:4 to C20:3, an index of Delta 5 desaturase activity, was significan tly 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 r ats fed 40% fructose. Bezafibrate increased Delta 5 desaturase activit y. Such action may contribute to the improvement of insulin sensitivit y.