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Titolo:
THE EFFECTS OF FIBRATES AND THIAZOLIDINEDIONES ON PLASMA TRIGLYCERIDE-METABOLISM ARE MEDIATED BY DISTINCT PEROXISOME PROLIFERATOR ACTIVATEDRECEPTORS (PPARS)
Autore:
STAELS B; SCHOONJANS K; FRUCHART JC; AUWERX J;
Indirizzi:
INST PASTEUR,U325,INSERM,DEPT ATHEROSCLEROSE,1 RUE CALMETTE F-59019 LILLE FRANCE
Titolo Testata:
Biochimie
fascicolo: 2-3, volume: 79, anno: 1997,
pagine: 95 - 99
SICI:
0300-9084(1997)79:2-3<95:TEOFAT>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
APOLIPOPROTEIN-C-III; LIPOPROTEIN-LIPASE DEFICIENCY; CIII GENE-EXPRESSION; RICH LIPOPROTEINS; TRANSGENIC MICE; SERUM-LIPIDS; A-I; HYPERTRIGLYCERIDEMIA; FENOFIBRATE; RAT;
Keywords:
GENE EXPRESSION; NUCLEAR RECEPTORS; APOLIPOPROTEINS; LIPOPROTEIN LIPASE; TRIGLYCERIDE METABOLISM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
39
Recensione:
Indirizzi per estratti:
Citazione:
B. Staels et al., "THE EFFECTS OF FIBRATES AND THIAZOLIDINEDIONES ON PLASMA TRIGLYCERIDE-METABOLISM ARE MEDIATED BY DISTINCT PEROXISOME PROLIFERATOR ACTIVATEDRECEPTORS (PPARS)", Biochimie, 79(2-3), 1997, pp. 95-99

Abstract

The hypolipidemic fibrates and antidiabetic thiazolidinediones display potent triglyceride-lowering activities. Studies on the molecular action mechanisms of these compounds indicate that thiazolidinediones and fibrates exert their action by activating distinct transcription factors of the peroxisome proliferator activated receptor (PPAR) family, resulting in increased expression of lipoprotein lipase (LPL) and decreased expression of apolipoprotein (apo) C-III, both key-players in plasma triglyceride metabolism. Fibrates, on the one hand, are PPAR alpha activators, which selectively induce LPL mRNA levels and activity inthe liver. Furthermore, hepatic apo C-III mRNA levels and protein production strongly decrease after fibrate treatment. On the other hand, thiazolidinediones, which are high affinity ligands for PPAR gamma, have no effect in the liver, but act primarily on adipose tissue, where they induce LPL mRNA levels and activity. The modulation of the expression of the LPL and apo C-III genes in liver and adipose tissue is correlated with the tissue-specific distribution of the respective PPARs (PPAR gamma expression being restricted to adipose tissue, whereas PPAR alpha is expressed predominantly in liver) confirming that fibrates and thiazolidinediones exert their effects primarily through PPAR alpha and PPAR gamma respectively. This distinct tissue-specific transcriptional regulation of genes involved in lipid metabolism by fibrates and thiazolidinediones indicates that research of compounds displaying combined PPAR alpha and PPAR gamma activation potential should lead to the discovery of more potent triglyceride lowering drugs, which may beof use in the treatment of hypertriglyceridemia.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 15/08/20 alle ore 20:00:27