PPARα Expression Protects Male Mice from High Fat-Induced Nonalcoholic Fatty Liver
PPARα Expression Protects Male Mice from High Fat-Induced Nonalcoholic Fatty Liver
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DOI：
10.3945/jn.110.135210
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发表时间：
2011-04-01
影响因子：
4.2
通讯作者：
Song, Byoung-Joon
中科院分区：
文献类型：
--
作者：
Abdelmegeed, Mohamed A.;Yoo, Seong-Ho;Song, Byoung-Joon
新出现的证据表明，当PPARα缺乏时，当喂食高脂饮食(HFD)时，PPARα的缺乏会加剧Ppara缺失小鼠的肝脏脂肪变性和炎症。因此，这项研究的目的是确定在短期喂养HFD后，Ppara基因缺失的小鼠是否比它们的野生型(WT)小鼠更容易患上非酒精性脂肪性肝炎(NASH)。年龄匹配的雄性WT和Ppara-Null小鼠被随机分配到标准Lieber-DeCarli液体饮食(STD)(35%来自脂肪)或HFD(71%来自脂肪)，持续3wk。评估所有组的肝脏组织学、血浆转氨酶水平、氧化/亚硝化应激指标和炎性细胞因子。HFD暴露组小鼠的小叶炎症水平和NASH活性评分均高于其他3组。生化分析显示，在Ppara缺失型小鼠中，乙醇诱导的细胞色素P450 2E1和肿瘤坏死因子α水平升高，同时丙二醛以及氧化和硝化蛋白水平增加。氧化应激和炎症的增加与c-jun-N末端激酶和p38激酶的激活有关，导致喂饲HFD的Ppara基因缺失的小鼠肝细胞凋亡增加。这些结果表明，PPARα功能的抑制可能会增加高脂诱导的NASH的易感性。这些结果表明，PPARα功能的抑制可能会增加高脂诱导的NASH的敏感性。J.Nutr.141：603-610,2011。
Emerging evidence suggests that the lack of PPAR alpha enhances hepatic steatosis and inflammation in Ppara-null mice when fed a high-fat diet (HFD). Thus, the aim of this study was to determine whether Ppara-null mice are more susceptible to nonalcoholic steatohepatitis (NASH) than their wild-type (WT) counterparts following short-term feeding with a HFD. Age-matched male WT and Ppara-null mice were randomly assigned to consume ad libitum a standard Lieber-DeCarli liquid diet (STD) (35% energy from fat) or a HFD (71% energy from fat) for 3 wk. Liver histology, plasma transaminase levels, and indicators of oxidative/nitrosative stress and inflammatory cytokines were evaluated in all groups. Levels of lobular inflammation and the NASH activity score were greater in HFD-exposed Ppara-null mice than in the other 3 groups. Biochemical analysis revealed elevated levels of ethanol-inducible cytochrome P450 2E1 and TNF alpha accompanied by increased levels of malondialdehyde as well as oxidized and nitrated proteins in Ppara-null mice. Elevated oxidative stress and inflammation were associated with activation of c-Jun-N-terminal kinase and p38 kinase, resulting in increased hepatocyte apoptosis in Ppara-null mice fed a HFD. These results, with increased steatosis, oxidative stress, and inflammation observed in Ppara-null mice fed a HFD, demonstrate that inhibition of PPAR alpha functions may increase susceptibility to high fat induced NASH. J. Nutr. 141: 603-610, 2011.