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Titolo:
Diabetic KKA(y) mice exhibit increased hepatic PPAR gamma 1 gene expression and develop hepatic steatosis upon chronic treatment with antidiabetic thiazolidinediones
Autore:
Bedoucha, M; Atzpodien, E; Boelsterli, UA;
Indirizzi:
Hoffmann La Roche Ag, Dept Nonclin Drug Safety, CH-4070 Basel, SwitzerlandHoffmann La Roche Ag Basel Switzerland CH-4070 H-4070 Basel, Switzerland
Titolo Testata:
JOURNAL OF HEPATOLOGY
fascicolo: 1, volume: 35, anno: 2001,
pagine: 17 - 23
SICI:
0168-8278(200107)35:1<17:DKMEIH>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROLIFERATOR-ACTIVATED RECEPTORS; FATTY-ACID OXIDATION; PPAR-GAMMA; ADIPOSE-TISSUE; INSULIN SENSITIZER; MESSENGER-RNA; IN-VITRO; TROGLITAZONE; LIVER; ALPHA;
Keywords:
non-insulin-dependent diabetes mellitus; thiazolidinediones; troglitazone; rosiglitazone; peroxisome proliferator-activated receptor-gamma; hepatic steatosis; KKA(y) mice; drug-induced hepatotoxicity; ob/ob mice;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Boelsterli, UA HepaTox, POB 14, CH-4148 Pfeffingen, Switzerland HepaTox POB 14 Pfeffingen Switzerland CH-4148 Switzerland
Citazione:
M. Bedoucha et al., "Diabetic KKA(y) mice exhibit increased hepatic PPAR gamma 1 gene expression and develop hepatic steatosis upon chronic treatment with antidiabetic thiazolidinediones", J HEPATOL, 35(1), 2001, pp. 17-23

Abstract

Background/Aims: Peroxisome proliferator-activated receptor-gamma, which is involved in the regulation of lipid homeostasis, is upregulated in the liver of obese and diabetic mice, but the biological consequences of this induction are largely unknown. This study was aimed at further characterizing this upregulation and exploring the downstream biological effects of specific activators on hepatic lipid metabolism. Methods: Hepatic expression of peroxisome proliferator-activated receptor-gamma1 and gamma2 mRNA and protein was analyzed by real-time polymerase chain reaction and Western immunoblotting in KKA(y) mice and ob/ob mice. KKA(y) mice were treated with thiazolidinediones, and hepatic triglyceride content and lipid distribution were analyzed biochemically and by histopathology. Results: KKA(y) mice exhibited a marked increase in hepatic peroxisome proliferator-activated receptor-gamma1 mRNA and protein levels, whereas the gamma2 isoform was upregulated in ob/ob mice. Treatment of KKA(y) mice with troglitazone or rosiglitazone resulted in severe microvesicular periacinar steatosis, whereas lean control mice did not develop any pathological liver changes. Hepatic triglyceride levels, however, were not altered by the treatment. Conclusions: In mice with obesity-associated upregulated hepatic peroxisome proliferator-activated receptor-gamma expression, thiazolidinediones may produce hepatic steatosis. Under pathophysiological conditions, such as non-insulin-dependent diabetes, the liver may thus become sensitized towards peroxisome proliferator-activated receptor-gamma -activating drugs. (C) 2001European Association for the Study of the Liver. Published by 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 25/11/20 alle ore 00:11:28