Gene Expression Changes Induced by PPAR Gamma Agonists in Animal and Human Liver
Thiazolidinediones are a class of Peroxisome Proliferator Activated Receptor γ (PPARγ) 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 induce...
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| Format: | Article |
| Language: | English |
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Wiley
2010-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2010/325183 |
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| author | Alexandra Rogue Catherine Spire Manuel Brun Nancy Claude André Guillouzo |
| author_facet | Alexandra Rogue Catherine Spire Manuel Brun Nancy Claude André Guillouzo |
| author_sort | Alexandra Rogue |
| collection | DOAJ |
| description | Thiazolidinediones are a class of Peroxisome Proliferator Activated Receptor γ (PPARγ) 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 PPARγ is expressed at a much lower level in liver than in adipose tissue, PPARγ agonists exert various PPARγ-dependent effects in liver in addition to PPARγ-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. |
| format | Article |
| id | doaj-art-e9bb426ae4a94c31ba93dac129512ba8 |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-e9bb426ae4a94c31ba93dac129512ba82025-08-20T03:26:34ZengWileyPPAR Research1687-47571687-47652010-01-01201010.1155/2010/325183325183Gene Expression Changes Induced by PPAR Gamma Agonists in Animal and Human LiverAlexandra Rogue0Catherine Spire1Manuel Brun2Nancy Claude3André Guillouzo4UMR INSERM U991, Faculté des Sciences Pharmaceutiques et Biologiques, 35043 Rennes, FranceBiologie Servier, 45520 Gidy, FranceInstitut de Recherches Servier, 92150 Suresnes, FranceInstitut de Recherches Servier, 92400 Courbevoie, FranceUMR INSERM U991, Faculté des Sciences Pharmaceutiques et Biologiques, 35043 Rennes, FranceThiazolidinediones are a class of Peroxisome Proliferator Activated Receptor γ (PPARγ) 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 PPARγ is expressed at a much lower level in liver than in adipose tissue, PPARγ agonists exert various PPARγ-dependent effects in liver in addition to PPARγ-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.http://dx.doi.org/10.1155/2010/325183 |
| spellingShingle | Alexandra Rogue Catherine Spire Manuel Brun Nancy Claude André Guillouzo Gene Expression Changes Induced by PPAR Gamma Agonists in Animal and Human Liver PPAR Research |
| title | Gene Expression Changes Induced by PPAR Gamma Agonists in Animal and Human Liver |
| title_full | Gene Expression Changes Induced by PPAR Gamma Agonists in Animal and Human Liver |
| title_fullStr | Gene Expression Changes Induced by PPAR Gamma Agonists in Animal and Human Liver |
| title_full_unstemmed | Gene Expression Changes Induced by PPAR Gamma Agonists in Animal and Human Liver |
| title_short | Gene Expression Changes Induced by PPAR Gamma Agonists in Animal and Human Liver |
| title_sort | gene expression changes induced by ppar gamma agonists in animal and human liver |
| url | http://dx.doi.org/10.1155/2010/325183 |
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