Catalogo Articoli (Spogli Riviste)

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Titolo:
A potent PPAR alpha agonist stimulates mitochondrial fatty acid beta-oxidation in liver and skeletal muscle
Autore:
Minnich, A; Tian, N; Byan, L; Bilder, G;
Indirizzi:
Aventis Pharmaceut Res & Dev, Dept Cardiovasc Biol, Collegeville, PA 19426USA Aventis Pharmaceut Res & Dev Collegeville PA USA 19426 ville, PA 19426USA
Titolo Testata:
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
fascicolo: 2, volume: 280, anno: 2001,
pagine: E270 - E279
SICI:
0193-1849(200102)280:2<E270:APPAAS>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROLIFERATOR-ACTIVATED RECEPTOR; CARNITINE PALMITOYLTRANSFERASE-I; TRIGLYCERIDE-RICH LIPOPROTEINS; PEROXISOME PROLIFERATORS; GENE-TRANSCRIPTION; TRANSPORT PROTEIN; APOLIPOPROTEIN C; RAT-LIVER; EXPRESSION; METABOLISM;
Keywords:
fibrates; carnitine palmitoyltransferase I; nuclear receptors; gene expression; peroxisome proliferator-activated receptor;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Minnich, A Aventis Pharmaceut, Div Resp Dis & Rheumatoid Arthrit, Rt 202-206, Bridgewater, NJ 08807 USA Aventis Pharmaceut Rt 202-206 Bridgewater NJ USA 08807 8807 USA
Citazione:
A. Minnich et al., "A potent PPAR alpha agonist stimulates mitochondrial fatty acid beta-oxidation in liver and skeletal muscle", AM J P-ENDO, 280(2), 2001, pp. E270-E279

Abstract

The proposed mechanism for the triglyceride (TG) lowering by fibrate drugsis via activation of the peroxisome proliferator-activated receptor-alpha (PPAR alpha). Here we show that a PPAR alpha agonist, ureido-fibrate-5 (UF-5), similar to 200-fold more potent than fenofibric acid, exerts TG-lowering effects (37%) in fat-fed hamsters after 3 days at 30 mg/kg. In addition to lowering hepatic apolipoprotein C-III (apoC-III) gene expression by similar to 60%, UF-5 induces hepatic mitochondrial carnitine palmitoyltransferase I (CPT I) expression. A 3-wk rising-dose treatment results in a greater TG-lowering effect (70%) at 15 mg/kg and a 2.3-fold elevation of muscle CPT I mRNA levels, as well as effects on hepatic gene expression. UF-5 also stimulated mitochondrial [H-3] palmitate beta -oxidation in vitro in human hepatic and skeletal muscle cells 2.7- and 1.6-fold, respectively, in a dose-related manner. These results suggest that, in addition to previously described effects of fibrates on apoC-III expression and on peroxisomal fatty acid (FA) beta -oxidation, PPAR alpha agonists stimulate mitochondrial FA beta-oxidation in vivo in both liver and muscle. These observations suggest animportant mechanism for the biological effects of PPAR alpha agonists.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/10/20 alle ore 03:43:22