Long-term alpha1-adrenergic blockade attenuates diet-induced dyslipidemia and hyperinsulinemia in the rat.
This study evaluated the ability of alpha1-adrenergic blockade to interfere with the development of diet-induced hyperlipidemia and deterioration of insulin action. Diets having extremely divergent effects on glucose and lipid metabolism were contrasted. Rats were fed for 4 weeks either a nonpurified diet (chow) or a hyperlipidemic (HL) purified diet containing 40% energy as sucrose, 40% as fat, and 20% as casein. Half of each dietary cohort was given the alpha1-adrenergic antagonist prazosin (3 mg/kg/day in the food). Blood was collected in the fasted state (10 h after food removal) and 2 h after the intake of a meal. In the fasted state, plasma triacylglycerols (TGs) were higher in rats fed the HL diet than in those given chow and were not affected by long-term treatment with prazosin. Postprandially, plasma TG increased twofold in the chow-fed group, with or without long-term prazosin. In contrast, prazosin reduced by more than half the eightfold increase in TG that followed intake of the high-fat meal (Diet x Blocker interaction; p < 0.002) in the HL cohort. The HL-fed animals also displayed fasting hypercholesterolemia (+30%; p < 0.0001), which was prevented by long-term treatment with prazosin. Likewise, the 50% increase in plasma cholesterol that followed meal ingestion only in the HL cohort was blunted by the alpha1-blocker (Diet x Blocker interaction; p < 0.001). Long-term prazosin also abolished fasting hyperinsulinemia in the HL cohort, whereas it did not alter fasting insulin in chow-fed animals (Diet x Blocker interaction; p < 0.005). Measurement of postprandial lipoprotein lipase activity in several tissues did not suggest the involvement of changes in the absolute availability of the enzyme as a determinant of the hypotriacylglycerolemic action of the alpha1-blocker. Thus long-term alpha1-adrenergic blockade, with minimal effects in rats fed a hypolipidemic diet, strongly attenuates several of the fasting and postprandial alterations in plasma variables of lipid and glucose metabolism induced by an extremely lipogenic diet.
Fajardo
N
N
Department of Physiology, School of Medicine, Laval University, Québec, Québec, Canada.
Deshaies
Y
Y
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D004032:Diet; D004041:Dietary Fats / Q000009:adverse effects; D005215:Fasting; D006946:Hyperinsulinism / Q000209:etiology / Q000517:prevention & control*; D006949:Hyperlipidemias / Q000209:etiology / Q000517:prevention & control*; D008071:Lipoprotein Lipase / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D001786:Blood Glucose; D004041:Dietary Fats; D008071:Lipoprotein Lipase