Improved insulin sensitivity by bezafibrate in rats: relationship to fatty acid composition of skeletal-muscle triglycerides.
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 x kg-1 x 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 high-fructose 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 delta5 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 delta5 desaturase activity. Such action may contribute to the improvement of insulin sensitivity.
Matsui
H
H
Internal Medicine II, Nagoya University School of Medicine, Japan.
Okumura
K
K
Kawakami
K
K
Hibino
M
M
Toki
Y
Y
Ito
T
T
D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D000090943:Delta-5 Fatty Acid Desaturase; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D044943:Fatty Acid Desaturases / Q000378:metabolism; D005227:Fatty Acids / Q000032:analysis*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005632:Fructose / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010743:Phospholipids / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000737:chemistry / Q000378:metabolism*
D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D000090943:Delta-5 Fatty Acid Desaturase; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D010743:Phospholipids; D014280:Triglycerides; D005632:Fructose; D002784:Cholesterol; D044943:Fatty Acid Desaturases; C029310:lard; D001629:Bezafibrate