title: Studies with etofibrate in the rat. Part I: Effects on glycerol, free fatty acid and triacylglycerol metabolism.
abstract: Etofibrate is the 1,2-ethandiol diester of clofibric acid and nicotinic acid that decreases circulating levels of triacylglycerols and cholesterol. To understand the mechanism by which the drug affects plasma triacylglycerols, normolipemic rats were treated daily with 300 mg of etofibrate/kg body weight or with the medium by a stomach tube. They were decapitated on the 10th day, and showed lower levels of plasma beta-hydroxybutyrate, glycerol, free fatty acids (FFA), total triacylglycerols and cholesterol and VLDL triacylglycerols and cholesterol, whereas glucose and RIA-determined insulin levels were unmodified. Epididymal fat pad pieces from etofibrate-treated rats incubated in vitro released more glycerol but the same amount of FFA to the medium, and had greater uptake of [U-14C]glycerol for [14C]acylglycerol formation. In the presence of heparin, they also showed an enhanced release of lipoprotein lipase activity to the medium. The disappearance from plasma of intravenously administered [1-14C]palmitate was faster in the etofibrate-treated rats, and although they showed a decrease in 14C-esterified fatty acids of neutral lipids in both liver and plasma VLDL, there was an increase in liver 14C-labelled water-soluble components. After intravenous [U-14C]glycerol administration, there was a decrease in plasma VLDL [14C]acylglycerol and [14C]glucose and in liver [14C]acylglycerol, but an increase in plasma [14C]lactate. In the liver, etofibrate treatment heightened the cytosolic glycerol-3-phosphate dehydrogenase activity and the total carnitine concentration, whereas it reduced triacylglycerol and cholesterol concentrations. It is proposed that etofibrate enhances the reesterification of fatty acids and glycerol in adipose tissue, which, together with its augmented lipoprotein lipase activity, may facilitate the clearance of circulating triacylglycerols. These effects may act concomitantly with the decreased synthesis of triacylglycerols, secondary to the increased utilization of their precursors, acyl-CoA and glycerol-3-phosphate, in other pathways, causing the reduction of plasma VLDL triacylglycerols produced by etofibrate treatment.
authors.affiliation: Departamento de Bioquímica, Universidad de Alcalá de Henares, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Herrera
authors.forename: M A
authors.initials: MA
authors.lastname: Lasunción
authors.forename: M
authors.initials: M
authors.lastname: Castro
authors.forename: D
authors.initials: D
authors.lastname: Gómez-Coronado
authors.forename: A
authors.initials: A
authors.lastname: Martín
authors.forename: G
authors.initials: G
authors.lastname: Quack
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D002994:Clofibrate / Q000031:analogs & derivatives*; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005990:Glycerol / Q000097:blood*; D008066:Lipolysis / Q000187:drug effects; D008079:Lipoproteins, VLDL / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects; D008297:Male; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D014280:Triglycerides / Q000096:biosynthesis / Q000097:blood*
chemical_list: D005230:Fatty Acids, Nonesterified; D008079:Lipoproteins, VLDL; D010169:Palmitic Acids; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; C009746:etofibrate; D019308:Palmitic Acid; D002995:Clofibric Acid; D002994:Clofibrate; D005990:Glycerol