Effects of high dietary fat and cholesterol on expression of PPARα, LXRα, and their responsive genes in the liver of apoE and LDLR double deficient mice
Effects of high dietary fat and cholesterol on expression of PPARα, LXRα, and their responsive genes in the liver of apoE and LDLR double deficient mice
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高脂肪和高胆固醇对apoE和LDLR双缺陷小鼠肝脏中PPARα、LXRα及其反应基因表达的影响
DOI：
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发表时间：
2009
影响因子：
4.3
通讯作者：
Jie Pan
中科院分区：
文献类型：
--
作者：
Ya;Hui;M. Yin;Liang Zhang;Liu;Ning Xiao;Guocheng Ren;Cong Zhang;Jie Pan
研究了高脂高胆固醇（HF）饲粮喂养的载脂蛋白E和低密度脂蛋白受体双缺陷（AL）小鼠中转录因子PPARα、LXRα及其应答/靶基因在动脉粥样硬化发病中的意义。以C57BL/6J野生型（WT）小鼠作为AL小鼠的对照。测定血浆脂质代谢物和主动脉壁形态动脉粥样硬化病变。采用半定量RT-PCR和实时定量RT-PCR检测AL小鼠与饲喂HF或正常鼠粮的对照组之间的基因表达谱。结果表明，饲喂HF日粮的AL小鼠，在12周的饲养期内，血浆脂质水平、肝脏脂质积累和动脉粥样硬化水平显著升高，PPARα、LXRα及其靶基因FAT、SCD1、FAS、Angptl3和apoB100的表达上调。apoAI、apoAIV、apoF、LPL和SR-BI均较低。HF处理后，WT小鼠PPARα、LXRα、FAS、Angpt13、CPT1、apoF、ACOX1、LPL、SR-BI显著升高，apoAI、apoAIV显著降低。饲喂HF日粮或鼠粮的AL和WT小鼠脂质代谢相关基因的不同变化表明，饮食对基因突变小鼠的影响机制与正常WT小鼠不同。由于AL小鼠脂质代谢系统存在遗传缺陷，我们认为ppara α、LXRα及其靶基因的改变加重了HF饲粮应激下AL小鼠肝脏脂质代谢紊乱，进一步加速了动脉粥样硬化的发展。
The significance of transcription factors PPARα, LXRα, and their responsive/target genes for the pathogenesis of atherosclerosis in apolipoprotein E and low-density lipoprotein receptor double deficient (AL) mice fed with high fat and cholesterol (HF) diet were studied. C57BL/6J wild-type (WT) mice were used as control to the AL mice. Plasma lipid metabolites and morphological atherosclerotic lesions in aortic wall were determined. Semi- and real-time quantitative RT-PCR were used to measure gene expression patterns between AL mice and the controls, which were fed with HF or normal chow diet. The results showed that in AL mice fed with HF diet, plasma lipid levels, hepatic lipid accumulation, and atherogenesis together with upregulated PPARα, LXRα, and their target genes, i.e., FAT, SCD1, FAS, Angptl3, and apoB100 significantly increased in a 12-week long feeding period. In contrast, apoAI, apoAIV, apoF, LPL, and SR-BI were decreased compared to chow-fed group. In WT mice, PPARα, LXRα, FAS, Angpt13, CPT1, apoF, ACOX1, LPL, and SR-BI were increased with HF treatment, while apoAI and apoAIV were decreased markedly. The different changes of lipid metabolism-related genes between AL and WT mice, fed with HF diet or chow diet indicated that the mechanisms of dietary effects on gene mutant mice are different from those of intact WT mice. Since lipid metabolic system defected genetically in AL mice, we suggest that the changes of PPARα, LXRα, and their target genes aggravated lipid metabolic disorder in the liver and further accelerated the development of atherosclerosis on a stress of HF diet feeding in AL mice.
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高密度和低密度脂蛋白的摄取和降解的位点和机制。
影响因子：
6.5
作者：
Pittman,RC;Steinberg,D
通讯作者：
Steinberg,D
DOI：
10.1016/s0021-9258(20)71160-9
发表时间：
1985-01
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Christopher;Ray C. Pittman;Morton Civen;Daniel Steinberg
通讯作者：
Christopher;Ray C. Pittman;Morton Civen;Daniel Steinberg
影响因子：
56.9
作者：
BROWN, MS;GOLDSTEIN, JL
通讯作者：
GOLDSTEIN, JL
DOI：
10.1073/pnas.91.20.9607
发表时间：
1994-09-27
影响因子：
11.1
作者：
PLUMP, AS;SCOTT, CJ;BRESLOW, JL
通讯作者：
BRESLOW, JL
DOI：
10.1152/ajpheart.1998.274.5.h1836
发表时间：
1998-05-01
影响因子：
4.8
作者：
Qin, XF;Swertfeger, DK;Tso, P
通讯作者：
Tso, P