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Titolo:
Induction of the phospholipid transfer protein gene accounts for the high density lipoprotein enlargement in mice treated with fenofibrate
Autore:
Bouly, M; Masson, D; Gross, B; Jiang, XC; Fievet, C; Castro, G; Tall, AR; Fruchart, JC; Staels, B; Lagrost, L; Luc, G;
Indirizzi:
Inst Pasteur, INSERM U545, Dept Atherosclerosis, F-59019 Lille, France Inst Pasteur Lille France F-59019 Atherosclerosis, F-59019 Lille, France Univ Lille 2, Fac Pharm, F-59006 Lille, France Univ Lille 2 Lille FranceF-59006 le 2, Fac Pharm, F-59006 Lille, France Hop Bocage, INSERM U498, Lab Lipoprot Biochem, Dijon, France Hop Bocage Dijon France NSERM U498, Lab Lipoprot Biochem, Dijon, France Columbia Univ, Dept Med, Div Mol Med, New York, NY 10032 USA Columbia Univ New York NY USA 10032 , Div Mol Med, New York, NY 10032 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 28, volume: 276, anno: 2001,
pagine: 25841 - 25847
SICI:
0021-9258(20010713)276:28<25841:IOTPTP>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROLIFERATOR-ACTIVATED RECEPTOR; APOLIPOPROTEIN-A-I; ADENOVIRUS-MEDIATED OVEREXPRESSION; TISSUE-SELECTIVE MANNER; ESTER TRANSFER PROTEIN; HUMAN-PLASMA; TRANSGENIC MICE; HEPATIC LIPASE; PARTICLE-SIZE; HDL LEVELS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Luc, G Inst Pasteur, INSERM U545, Dept Atherosclerosis, 1 Rue Prof Calmette, F-59019 Lille, France Inst Pasteur 1 Rue Prof Calmette Lille France F-59019 ille, France
Citazione:
M. Bouly et al., "Induction of the phospholipid transfer protein gene accounts for the high density lipoprotein enlargement in mice treated with fenofibrate", J BIOL CHEM, 276(28), 2001, pp. 25841-25847

Abstract

Fibrate treatment in mice is known to modulate high density lipoprotein (HDL) metabolism by regulating apolipoprotein (apo)AI and apoAII gene expression. In addition to alterations in plasma HDL levels, fibrates induce the emergence of large, cholesteryl ester-rich HDL in treated transgenic mice expressing human apoAI (HuAITg), The mechanisms of these changes may not be restricted to the modulation of apolipoprotein gene expression, and the aim of the present study was to determine whether the expression of factors known to affect HDL metabolism (ie. phospholipid transfer protein (PLTP), lecithin:cholesterol acyltransferase, and hepatic lipase) are modified in fenofibrate-treated mice. Significant rises in plasma PLTP activity were observed after 2 weeks of fenofibrate treatment in both wild-type and HuAITg mice. Simultaneously, hepatic PLTP mRNA levels increased in a dose-dependent fashion. In contrast to PLTP, lecithin: cholesterol acyltransferase mRNA levels in HuAITg mice were not significantly modified by fenofibrate despite a significant decrease in plasma cholesterol esterification activity, Fenofibrate did not induce any change in hepatic lipase activity. Fenofibrate significantly increased HDL size, an effect that was more pronounced in HuAITg mice than in wild-type mice, This effect in wild-type mice was completely abolished in PLTP-deficient mice. Finally, fenofibrate treatment did not influence PLTP activity or hepatic mRNA in peroxisome proliferator-activated receptor-alpha -deficient mice. It is concluded that 1) fenofibrate treatmentincreases plasma phospholipid transfer activity as the result of up-regulation of PLTP gene expression through a peroxisome proliferator-activated receptor-alpha -dependent mechanism, and 2) increased plasma PLTP levels account for the marked enlargement of HDL in fenofibrate-treated mice.

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Documento generato il 12/07/20 alle ore 08:34:50