PPARalpha: energy combustion, hypolipidemia, inflammation and cancer.
PPARalpha: energy combustion, hypolipidemia, inflammation and cancer.
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DOI：
10.1621/nrs.08002
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发表时间：
2010-04-16
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影响因子：
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通讯作者：
Reddy, Janardan K
中科院分区：
文献类型：
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作者：
Pyper, Sean R;Viswakarma, Navin;Reddy, Janardan K
过氧化物酶体增殖物激活受体α(PPARpha，或NR1C1)是一种核激素受体，由一系列结构不同的合成化学物质激活，称为过氧化物酶体增殖物。在某些脂质代谢的基因敲除小鼠模型中，也观察到肝脏中PPARpha的内源性激活，这意味着存在产生(合成)或降解内源性PPARpha激动剂的酶。例如，参与脂肪酸氧化的底物可以作为PPARpha配体发挥作用。PPARpha是一种外源生物和脂质传感器，可调节能量燃烧、肝脏脂肪变性、脂蛋白合成、炎症和肝癌。PPARpha主要调节所有三种脂肪酸氧化系统的活性，即线粒体和过氧化体的β-氧化以及微粒体的omega-氧化，因此在能量消耗中起关键作用。外源性或内源性激动剂对PPARα的持续激活可导致肝细胞癌的发生，其原因是持续的氧化应激和可能的内质网应激以及肝细胞的增殖。PPARpha的转录活性需要转录共激活因子PPAR结合蛋白(PBP)/介体亚单位1(MED1)。
The peroxisome proliferator-activated receptor alpha (PPARalpha, or NR1C1) is a nuclear hormone receptor activated by a structurally diverse array of synthetic chemicals known as peroxisome proliferators. Endogenous activation of PPARalpha in liver has also been observed in certain gene knockout mouse models of lipid metabolism, implying the existence of enzymes that either generate (synthesize) or degrade endogenous PPARalpha agonists. For example, substrates involved in fatty acid oxidation can function as PPARalpha ligands. PPARalpha serves as a xenobiotic and lipid sensor to regulate energy combustion, hepatic steatosis, lipoprotein synthesis, inflammation and liver cancer. Mainly, PPARalpha modulates the activities of all three fatty acid oxidation systems, namely mitochondrial and peroxisomal beta-oxidation and microsomal omega-oxidation, and thus plays a key role in energy expenditure. Sustained activation of PPARalpha by either exogenous or endogenous agonists leads to the development of hepatocellular carcinoma resulting from sustained oxidative and possibly endoplasmic reticulum stress and liver cell proliferation. PPARalpha requires transcription coactivator PPAR-binding protein (PBP)/mediator subunit 1(MED1) for its transcriptional activity.