Effects of ciprofibrate and fenofibrate on liver lipids and lipoprotein synthesis in normo- and hyperlipidemic rats.
The plasma lipoprotein and liver lipid composition, and the lipid, cholesterol and apolipoprotein synthesis have been studied in normal and diet-induced hyperlipidemic rats, receiving ciprofibrate (2.5 mg/kg body weight) or fenofibrate (50 mg/kg b.w.) for 8 days. Ciprofibrate is about 25-fold more active than fenofibrate in reducing plasma triglyceride and cholesterol concentrations both in normolipemic and in hyperlipemic rats. In normolipemic rats ciprofibrate reduced the concentration and the lipid content of all lipoprotein classes. The incorporation of [14C]palmitate and [3H]leucine into the lipoproteins was reduced by ciprofibrate and fenofibrate. The reduction in lipoprotein production was confirmed by prevention of Triton-induced hyperlipemia. Liver and plasma cholesterol synthesis estimated by 3H2O and [14C]mevalonate incorporation indicated an inhibitory effect on HMG-CoA reductase. Administration of ciprofibrate or fenofibrate to rats fed a fat and cholesterol-rich diet partially prevented liver steatosis and hyperlipemia. Both drugs reduced the overproduction of lower density lipoproteins. The ratio of (VLDL + LDL)-cholesterol/HDL-cholesterol which was increased by the diet alone from 0.4 (normal) to 11 remained close to the normal value in the animals receiving ciprofibrate. In the hyperlipemic animals, ciprofibrate reduced the incorporation of [3H]oleate into the liver and plasma glycerolipid and increased cholesterol esterification. Ciprofibrate efficiently reduces plasma levels of cholesterol, triglyceride and phospholipid. Cholesterol and glycerolipid synthesis in the liver were significantly reduced leading to a lower lipoprotein secretion rate in both normolipidemic and diet-induced hyperlipidemic rats.
Petit
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INSERM U9, Hôpital Saint-Antoine, Paris, France.
Bonnefis
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MT
Rey
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Infante
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D000818:Animals; D001053:Apolipoproteins / Q000096:biosynthesis; D002784:Cholesterol / Q000096:biosynthesis; D002994:Clofibrate / Q000031:analogs & derivatives*; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D011345:Fenofibrate / Q000494:pharmacology*; D058607:Fibric Acids; D006949:Hyperlipidemias / Q000378:metabolism*; D008055:Lipids / Q000096:biosynthesis* / Q000097:blood; D008074:Lipoproteins / Q000096:biosynthesis* / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D001053:Apolipoproteins; D058607:Fibric Acids; D008055:Lipids; D008074:Lipoproteins; D011422:Propionates; D002995:Clofibric Acid; D002784:Cholesterol; C019304:ciprofibrate; D002994:Clofibrate; D011345:Fenofibrate