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Titolo:
Disturbances in the normal regulation of SREBP-sensitive genes in PPAR alpha-deficient mice
Autore:
Patel, DD; Knight, BL; Wiggins, D; Humphreys, SM; Gibbons, GF;
Indirizzi:
Univ Oxford, Nuffield Dept Clin Med, Metab Res Lab, Oxford OX2 6HE, England Univ Oxford Oxford England OX2 6HE etab Res Lab, Oxford OX2 6HE, England Hammersmith Hosp, Imperial Coll Sch Med, MRC Clin Sci Ctr, Lipoprot Grp, London W12 0NN, England Hammersmith Hosp London England W12 0NN rot Grp, London W12 0NN, England Univ Oxford, Nuffield Dept Clin Med, Oxford Lipid Metab Grp, Oxford OX2 6HE, England Univ Oxford Oxford England OX2 6HE id Metab Grp, Oxford OX2 6HE, England
Titolo Testata:
JOURNAL OF LIPID RESEARCH
fascicolo: 3, volume: 42, anno: 2001,
pagine: 328 - 337
SICI:
0022-2275(200103)42:3<328:DITNRO>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROLIFERATOR-ACTIVATED RECEPTORS; LOW-DENSITY-LIPOPROTEIN; MESSENGER-RNA LEVELS; FATTY-ACID SYNTHESIS; RAT-LIVER; 3-HYDROXY-3-METHYLGLUTARYL COENZYME; CHOLESTEROL-BIOSYNTHESIS; REDUCTASE-ACTIVITY; CIRCADIAN-RHYTHM; DIURNAL RHYTHM;
Keywords:
cholesterol; fatty acids; liver; diurnal cycle; plasma; sterol regulatory element-binding protein; peroxisome proliferator-activated receptor;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Gibbons, GF Univ Oxford, Nuffield Dept Clin Med, Metab Res Lab, Oxford OX26HE, England Univ Oxford Oxford England OX2 6HE , Oxford OX2 6HE, England
Citazione:
D.D. Patel et al., "Disturbances in the normal regulation of SREBP-sensitive genes in PPAR alpha-deficient mice", J LIPID RES, 42(3), 2001, pp. 328-337

Abstract

Peroxisome proliferator-activated receptor alpha (PPAR alpha)-null mice were used to investigate the nature of the relationship between the normal circadian rhythm of hepatic PPAR alpha expression and the expression of the Lipogenic and cholesterogenic sterol regulatory element-binding protein (SREBP)-regulated genes, acetyl-CoA carboxylase, fatty acid synthase (FAS), and3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoAR), The expression of FASand HMG-CoAR varied rhythmically over the diurnal cycle in the normal mice, with patterns that were the opposite of that of PPAR alpha, The diurnal variation of lipogenic and cholesterogenic gene expression was attenuated orabolished in the PPAR alpha -null mice. This resulted in decreased expression compared with normal mice, but only during the dark phase of the cycle,when food intake was high. The diurnal variation in hepatic fatty acid andcholesterol synthesis was also abolished in the PPAR alpha -null animals and the variations in the concentration of plasma triacylglycerol, nonesterified fatty acids, and cholesterol were all attenuated. The failure of HMG-CoAR expression to increase during the feeding period in the PPAR alpha -null mice was associated with a decrease in hepatic nonesterified cholesterol content and an increase in cholesteryl ester compared with normal mice. There was no defect in the downregulation of hepatic HMG-CoAR mRNA in responseto dietary cholesterol in the PPAR alpha -null mice. Under these conditions, hepatic PPAR gamma expression increased in both the control and PPAR alpha -deficient mice. The results suggest that PPAR alpha -deficiency disturbs the normal circadian regulation of certain SREBP-sensitive genes in the liver, but does not affect their response to dietary cholesterol.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/11/20 alle ore 17:58:28