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Clin Invest Arterioscl 2003;15:248-57 - DOI: 10.1016/S0214-9168(03)78936-0
Estudio del mecanismo de acción hipolipemiante de la lovastatina en la rata
Study of the mechanism of hypolipemiant effect of lovastatin in the rat
I.C. López-Pérez, E. Relaño, E. Herrera, C. Bocos1,
Departamento de Biología Celular, Bioquímica y Biología Molecular. Facultad de Ciencias Experimentales y de la Salud. Universidad San Pablo-CEU. Madrid. España

Statins are hypolipidemic drugs that not only improve cholesterol but also triglyceride levels. Whereas their cholesterol-lowering effect involves inhibition of cholesterogenesis through inhibition of enzyme 3-hidroxy-methylglutaryl CoA (HMG-CoA) reductase, the mechanism by whichthey reduce triglycerides remains unknown. Peroxisome proliferator-activated receptor alpha (PPAR-α is crucial in lipid metabolism and has been related to the pharmacologic effect on triglyceridemia (as is the case of fibrates).


This study was carried out to determine the effect of acute administration of a high dose of lovastatin on hepatic expression of both PPAR-α and some of its target genes in normolipidemic rats. In parallel, the ex vivo lipolytic activity of white adipose tissue from the same rats was also studied.


Cholesterolemia was not affected by the drug at the times considered (1,5, 3 and 7 hours after administration of the drug) and, although triglyceridemia did not seem to be affected by the treatment, a hypotriglyceridemic effect was observed at 7 hours after administration. Expression of PPAR-α and its target gene, peroxisomal acyl-CoA oxidase (ACO) were similarly affected by the treatment, showing a trend to increase in treated animals. This increase was statistically significant at 7 hours. Expression of apolipoprotein CIII remained unchanged but that of phosphoenolpyruvate carboxykinase (PEPCK) seemed to be sensitive to the plasma FFA profile in both animal groups. Regarding adipose tissue lipolytic activity, the basal values, which increased throughout the study, were markedly reduced by lovastatin at 7 hours after administration. However, at 3 hours after administration adipose tissue from treated rats seemed to be more sensitive to epinephrine than tissue from control rats.


The results of this study suggest that the hypotriglyceridemic effect of lovastatin is related to both induction of hepatic expression of PPAR-α and genes related to peroxisomal oxidation, as well as to the antilipolytic effect on adipose tissue.

Palabras clave
Estatinas, PPAR, Expresión génica, Lipólisis, Triglicéridos
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Correspondencia: Dr. C. Bocos. Laboratorio de Biología Molecular. Facultad de Ciencias Experimentales y de la Salud. Universidad San Pablo-CEU. Ctra. Boadilla del Monte, km 5,300. 28668 Boadilla del Monte. Madrid. España. Correo electrónico:
Copyright © 2003. Sociedad Española de Arteriosclerosis y Elsevier España, S.L.