Gene Expression Changes Induced by PPAR Gamma Agonists in Animal and Human Liver

被引:100
作者
Rogue, Alexandra [1 ,2 ,3 ]
Spire, Catherine [1 ]
Brun, Manuel [4 ]
Claude, Nancy [5 ]
Guillouzo, Andre [2 ,3 ]
机构
[1] Biol Servier, F-45520 Gidy, France
[2] Fac Sci Pharmaceut & Biol, UMR INSERM U991, F-35043 Rennes, France
[3] Univ Rennes 1, F-35065 Rennes, France
[4] Inst Rech Servier, F-92150 Suresnes, France
[5] Inst Rech Servier, F-92400 Courbevoie, France
关键词
ACTIVATED-RECEPTOR-GAMMA; CELL-CYCLE ARREST; MESSENGER-RNA EXPRESSION; IN-VITRO; ADIPOSE-TISSUE; SKELETAL-MUSCLE; NUCLEAR RECEPTORS; PRIMARY CULTURES; TRANSCRIPTIONAL ACTIVITY; INSULIN SENSITIVITY;
D O I
10.1155/2010/325183
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Thiazolidinediones are a class of Peroxisome Proliferator Activated Receptor gamma (PPAR gamma) agonists that reduce insulin resistance in type 2 diabetic patients. Although no detectable hepatic toxicity has been evidenced in animal studies during preclinical trials, these molecules have nevertheless induced hepatic adverse effects in some treated patients. The mechanism(s) of hepatotoxicity remains equivocal. Several studies have been conducted using PCR analysis and microarray technology to identify possible target genes and here we review the data obtained from various in vivo and in vitro experimental models. Although PPAR gamma is expressed at a much lower level in liver than in adipose tissue, PPAR gamma agonists exert various PPAR gamma-dependent effects in liver in addition to PPAR gamma-independent effects. Differences in effects are dependent on the choice of agonist and experimental conditions in rodent animal studies and in rodent and human liver cell cultures. These effects are much more pronounced in obese and diabetic liver. Moreover, our own recent studies have shown major interindividual variability in the response of primary human hepatocyte populations to troglitazone treatment, supporting the occurrence of hepatotoxicity in only some individuals.
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页数:16
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共 88 条
  • [21] PPARα and PPARγ dual agonists for the treatment of type 2 diabetes and the metabolic syndrome
    Fievet, Catherine
    Fruchart, Jean-Charles
    Staels, Bart
    [J]. CURRENT OPINION IN PHARMACOLOGY, 2006, 6 (06) : 606 - 614
  • [22] Frederiksen KS, 2004, J LIPID RES, V45, P592, DOI 10.1194/jlr.M300239-JLR200
  • [23] Cholestatic potential of troglitazone as a possible factor contributing to troglitazone-induced hepatotoxicity: In vivo and in vitro interaction at the canalicular bile salt export pump (Bsep) in the rat
    Funk, C
    Ponelle, C
    Scheuermann, G
    Pantze, M
    [J]. MOLECULAR PHARMACOLOGY, 2001, 59 (03) : 627 - 635
  • [24] Liver peroxisome proliferator-activated receptor γ contributes to hepatic steatosis, triglyceride clearance, and regulation of body fat mass
    Gavrilova, O
    Haluzik, M
    Matsusue, K
    Cutson, JJ
    Johnson, L
    Dietz, KR
    Nicol, CJ
    Vinson, C
    Gonzalez, FJ
    Reitman, ML
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (36) : 34268 - 34276
  • [25] Expression profiling of interindividual variability following xenobiotic exposures in primary human hepatocyte cultures
    Goyak, Katy M. O.
    Johnson, Mary C.
    Strom, Stephen C.
    Omiecinski, Curtis J.
    [J]. TOXICOLOGY AND APPLIED PHARMACOLOGY, 2008, 231 (02) : 216 - 224
  • [26] Infection of a human hepatoma cell line by hepatitis B virus
    Gripon, P
    Rumin, S
    Urban, S
    Le Seyec, J
    Glaise, D
    Cannie, I
    Guyomard, C
    Lucas, J
    Trepo, C
    Guguen-Guillouzo, C
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (24) : 15655 - 15660
  • [27] Antineoplastic effects of peroxisome proliferator-activated receptor γ agonists
    Grommes, C
    Landreth, GE
    Heneka, MT
    [J]. LANCET ONCOLOGY, 2004, 5 (07) : 419 - 429
  • [28] Liver cell models in in vitro toxicology
    Guillouzo, A
    [J]. ENVIRONMENTAL HEALTH PERSPECTIVES, 1998, 106 : 511 - 532
  • [29] Evolving concepts in liver tissue modeling and implications for in vitro toxicology
    Guillouzo, Andre
    Guguen-Guillouzo, Christiane
    [J]. EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY, 2008, 4 (10) : 1279 - 1294
  • [30] Differential gene expression in mouse primary hepatocytes exposed to the peroxisome proliferator-activated receptor α agonists
    Guo, Lei
    Fang, Hong
    Collins, Jim
    Fan, Xiao-Hui
    Dial, Stacey
    Wong, Alex
    Mehta, Kshama
    Blann, Ernice
    Shi, Leming
    Tong, Weida
    Dragan, Yvonne P.
    [J]. BMC BIOINFORMATICS, 2006, 7 (Suppl 2)