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Titolo:
Regulation of lipid metabolism and gene expression by fenofibrate in hamsters
Autore:
Guo, Q; Wang, PR; Milot, DP; Ippolito, MC; Hernandez, M; Burton, CA; Wright, SD; Chao, YS;
Indirizzi:
Merck & Co Inc, Dept Atherosclerosis & Endocrinol, Rahway, NJ 07065 USA Merck & Co Inc Rahway NJ USA 07065 sis & Endocrinol, Rahway, NJ 07065 USA
Titolo Testata:
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
fascicolo: 3, volume: 1533, anno: 2001,
pagine: 220 - 232
SICI:
1388-1981(20011031)1533:3<220:ROLMAG>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
FATTY-ACID SYNTHASE; APOLIPOPROTEIN-A-I; PROLIFERATOR-ACTIVATED RECEPTORS; LIPOPROTEIN-LIPASE GENE; PPAR-GAMMA ACTIVATORS; C-III EXPRESSION; PEROXISOME PROLIFERATOR; CHOLESTEROL-METABOLISM; MESSENGER-RNA; MOLECULAR-CLONING;
Keywords:
hypolipidemia; gene regulation; hypolipidemic drug; fenofibrate; syrian hamster;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
77
Recensione:
Indirizzi per estratti:
Indirizzo: Guo, Q Merck & Co Inc, Dept Atherosclerosis & Endocrinol, R80W250,POB 2000, Rahway, NJ 07065 USA Merck & Co Inc R80W250,POB 2000 Rahway NJ USA 07065 y, NJ 07065 USA
Citazione:
Q. Guo et al., "Regulation of lipid metabolism and gene expression by fenofibrate in hamsters", BBA-MOL C B, 1533(3), 2001, pp. 220-232

Abstract

Fenofibrate is a potent hypolipidemic agent that lowers plasma lipid levels and may thus decrease the incidence of atherosclerosis. Here we investigated the molecular mechanism of fenofibrate's hypolipidemic action by characterizing its in vivo effects on the expression of mRNAs and the activities of pivotal enzymes in cholesterol and triglyceride metabolism in the hamster. Treatment of hamsters with fenofibrate led to a dose-dependent reductionin serum cholesterol concentrations. Studies on the incorporation of [C-14]acetate and [C-14]mevalonate into cholesterol suggested that this effect occurs primarily through inhibition of cholesterol biosynthesis at steps prior to mevalonate. Fenofibrate decreased levels of hepatic enzyme activitiesand mRNAs for 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) synthase andHMG CoA reductase. A potential mechanism for transcriptional regulation ofthese enzymes is via SREBP-2 that we found to be suppressed 2-fold by fenofibrate. Fenofibrate also lowered circulatory triglyceride levels. In keeping with the effect, we observed strong suppression of fatty acid synthase, acetyl-CoA carboxylase and apolipoprotein C-III mRNA and stimulation of lipoprotein lipase and acyl-CoA oxidase mRNA in the liver of fenofibrate-treated hamsters. These observations suggest that the effect of fenofibrate on triglyceride metabolism is likely to be a result of both decreased fatty acid synthesis and increased lipoprotein lipase and acyl-CoA oxidase gene expression in the liver. Surprisingly, alterations in lipoprotein lipase, acyl-CoA oxidase, acetyl-CoA carboxylase, and apolipoprotein C-III could not be observed in hamster hepatocytes incubated with fenofibric acid in vitro. These observations raise the possibility that changes in these genes may be secondary to the metabolic alterations occurring in animals but not in cultured cells and thus that the effect of fenofibrate on these genes may be indirect. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 18:33:16