Analysis of the role of hepatic PPARγ expression during mouse liver regeneration.
Analysis of the role of hepatic PPARγ expression during mouse liver regeneration.
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DOI：
10.1002/hep.25880
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发表时间：
2012-10
期刊：
影响因子：
13.5
通讯作者：
Rudnick, David A.
中科院分区：
文献类型：
--
作者：
Gazit, Vered;Huang, Jiansheng;Weymann, Alexander;Rudnick, David A.
接受部分肝切除术（PH）的小鼠出现低血糖，随后在肝细胞增殖开始之前全身脂肪分解和肝脂肪积累增加。破坏这些代谢事件的策略会抑制再生。这些观察结果表明，肝功能不全引起的代谢改变可促进肝再生。过氧化物酶体增殖物激活受体γ（PPARγ）的肝脏表达影响肝脏中的脂肪积累。因此，本文报道的研究旨在评估肝再生过程中肝脏 PPARγ 表达破坏对肝脂肪积累和肝细胞增殖的影响。结果表明，在维持正常饮食的肝脏特异性 PPARγ 缺失小鼠中，肝脏再生并未受到抑制，反而略有增强。这些动物还表现出肝细胞周期蛋白 D1 表达加速。由于在肝脏再生受损的脂肪肝病实验模型中，肝脏 PPARγ 表达增加，因此还检查了患有慢性肝脂肪变性的肝脏特异性 PPARγ 缺失小鼠的再生情况。与上述结果相反，饮食诱导的肝脂肪变性小鼠中肝脏 PPARγ 表达的破坏导致肝再生的显着抑制。这些研究表明，肝脏特异性 PPARγ 缺失小鼠的代谢和肝细胞增殖反应对 PH 略有增强，从而为肝脏再生的代谢模型提供了额外的支持。此外，在饮食诱导的慢性脂肪变性的情况下，肝脏特异性 PPARγ 缺失小鼠的再生受到显着损害，这表明增强肝脏 PPARγ 活性的药理学策略可能会改善脂肪肝的再生。
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 accumulation in the liver. Therefore, the studies reported here were undertaken to assess the effects of disruption of hepatic PPARγ 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 PPARγ null mice maintained on a normal diet. These animals also exhibited accelerated hepatic Cyclin D1 expression. Because hepatic PPARγ expression is increased in experimental models of fatty liver disease in which liver regeneration is impaired, regeneration in liver-specific PPARγ null mice with chronic hepatic steatosis was also examined. In contrast to the results described above, disruption of hepatic PPARγ expression in mice with diet-induced hepatic steatosis resulted in significant suppression of hepatic regeneration. These studies show that the metabolic and hepatocellular proliferative responses to PH are modestly augmented in liver-specific PPARγ null mice, thus providing additional support for a metabolic model of liver regeneration. Furthermore, regeneration is significantly impaired in liver-specific PPARγ null mice in the setting of diet-induced chronic steatosis, suggesting that pharmacological strategies to augment hepatic PPARγ activity might improve regeneration of the fatty liver.
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影响因子：
25.7
作者：
Fausto, N
通讯作者：
Fausto, N
影响因子：
15.9
作者：
Matsusue, K;Haluzik, M;Gonzalez, FJ
通讯作者：
Gonzalez, FJ
DOI：
10.1073/pnas.2536828100
发表时间：
2003-12-23
影响因子：
11.1
作者：
He, WM;Barak, Y;Evans, RM
通讯作者：
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作者：
Matsuo, T;Yamaguchi, S;Okamura, H
通讯作者：
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影响因子：
3.6
作者：
Petrovic V;Costa RH;Lau LF;Raychaudhuri P;Tyner AL
通讯作者：
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