Dataset Information

Analysis of the role of hepatic PPAR? expression during mouse liver regeneration.

ABSTRACT: Mice subjected to partial hepatectomy (PH) develop hypoglycemia, followed by increased systemic lipolysis and hepatic fat accumulation, prior to onset of hepatocellular proliferation. Strategies that disrupt these metabolic events inhibit regeneration. These observations suggest that alterations in metabolism in response to hepatic insufficiency promote liver regeneration. Hepatic expression of the peroxisome proliferator-activated receptor gamma (PPAR?) influences fat accumulation in the liver. Therefore, the studies reported here were undertaken to assess the effects of disruption of hepatic PPAR? expression on hepatic fat accumulation and hepatocellular proliferation during liver regeneration. The results showed that liver regeneration was not suppressed, but rather modestly augmented in liver-specific PPAR? null mice maintained on a normal diet. These animals also exhibited accelerated hepatic cyclin D1 expression. Because hepatic PPAR? expression is increased in experimental models of fatty liver disease in which liver regeneration is impaired, regeneration in liver-specific PPAR? null mice with chronic hepatic steatosis was also examined. In contrast to the results described above, disruption of hepatic PPAR? expression in mice with diet-induced hepatic steatosis resulted in significant suppression of hepatic regeneration.The metabolic and hepatocellular proliferative responses to PH are modestly augmented in liver-specific PPAR? null mice, thus providing additional support for a metabolic model of liver regeneration. Furthermore, regeneration is significantly impaired in liver-specific PPAR? null mice in the setting of diet-induced chronic steatosis, suggesting that pharmacological strategies to augment hepatic PPAR? activity might improve regeneration of the fatty liver.

SUBMITTER: Gazit V

PROVIDER: S-EPMC3465497 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Analysis of the role of hepatic PPARγ expression during mouse liver regeneration.

Gazit Vered V Huang Jiansheng J Weymann Alexander A Rudnick David A DA

Hepatology (Baltimore, Md.) 20121001 4

<h4>Unlabelled</h4>Mice subjected to partial hepatectomy (PH) develop hypoglycemia, followed by increased systemic lipolysis and hepatic fat accumulation, prior to onset of hepatocellular proliferation. Strategies that disrupt these metabolic events inhibit regeneration. These observations suggest that alterations in metabolism in response to hepatic insufficiency promote liver regeneration. Hepatic expression of the peroxisome proliferator-activated receptor gamma (PPARγ) influences fat accumul ...[more]

PMID: 22707117

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Project description:Adaptation to chronic ethanol (EtOH) treatment of rats results in a changed functional state of the liver and greatly inhibits its regenerative ability, which may contribute to the progression of alcoholic liver disease.In this study, we investigated the effect of chronic EtOH intake on hepatic microRNA (miRNA) expression in male Sprague-Dawley rats during the initial 24 hours of liver regeneration following 70% partial hepatectomy (PHx) using miRNA microarrays. miRNA expression during adaptation to EtOH was investigated using RT-qPCR. Nuclear factor kappa B (NF?B) binding at target miRNA promoters was investigated with chromatin immunoprecipitation.Unsupervised clustering of miRNA expression profiles suggested that miRNA expression was more affected by chronic EtOH feeding than by the acute challenge of liver regeneration after PHx. Several miRNAs that were significantly altered by chronic EtOH feeding, including miR-34a, miR-103, miR-107, and miR-122 have been reported to play a role in regulating hepatic metabolism and the onset of these miRNA changes occurred gradually during the time course of EtOH feeding. Chronic EtOH feeding also altered the dynamic miRNA profile during liver regeneration. Promoter analysis predicted a role for NF?B in the immediate-early miRNA response to PHx. NF?B binding at target miRNA promoters in the chronic EtOH-fed group was significantly altered and these changes directly correlated with the observed expression dynamics of the target miRNA.Chronic EtOH consumption alters the hepatic miRNA expression profile such that the response of the metabolism-associated miRNAs occurs during long-term adaptation to EtOH rather than as an acute transient response to EtOH metabolism. Additionally, the dynamic miRNA program during liver regeneration in response to PHx is altered in the chronically EtOH-fed liver and these differences reflect, in part, differences in miRNA expression between the EtOH-adapted and control livers at the baseline state prior to PHx.

Dataset Information

Analysis of the role of hepatic PPAR? expression during mouse liver regeneration.

Publications

Analysis of the role of hepatic PPARγ expression during mouse liver regeneration.

Similar Datasets

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