PPARα对脂质代谢的调节
中文名称
通路描述
过氧化物酶体增殖物激活受体α（PPARα）是肝脏中脂肪酸氧化的主要调节者。PPARα也是用于治疗异常血浆脂质水平的纤维药物靶点。PPARα是一种II型核受体（其亚细胞定位不依赖于配体结合）。PPARα与另一种II型核受体RXRα形成异二聚体。PPARα通过与脂肪酸配体结合而被激活，特别是含有18-22个碳原子和2-6个双键的多不饱和脂肪酸。PPARα:RXRα异二聚体结合在靶基因周围的过氧化物酶体增殖物反应元件（PPREs）。脂肪酸和合成配体的结合导致PPARα构象改变，使其释放共抑制因子并与共激活因子（CBP-SRC-HAT复合物、ASC复合物和TRAP-Mediator复合物）结合，从而启动靶基因的转录。PPARα的靶基因参与脂肪酸运输、脂肪酸氧化、甘油三酯清除、脂蛋白生产和胆固醇稳态。
英文描述
Regulation of lipid metabolism by PPARalpha Peroxisome proliferator-activated receptor alpha (PPAR-alpha) is the major regulator of fatty acid oxidation in the liver. PPARalpha is also the target of fibrate drugs used to treat abnormal plasma lipid levels.
PPAR-alpha is a type II nuclear receptor (its subcellular location does not depend on ligand binding). PPAR-alpha forms heterodimers with Retinoid X receptor alpha (RXR-alpha), another type II nuclear receptor. PPAR-alpha is activated by binding fatty acid ligands, especially polyunsaturated fatty acids having 18-22 carbon groups and 2-6 double bonds.
The PPAR-alpha:RXR-alpha heterodimer binds peroxisome proliferator receptor elements (PPREs) in and around target genes. Binding of fatty acids and synthetic ligands causes a conformational change in PPAR-alpha such that it releases the corepressors and binds coactivators (CBP-SRC-HAT complex, ASC complex, and TRAP-Mediator complex) which initiate transcription of the target genes.
Target genes of PPAR-alpha participate in fatty acid transport, fatty acid oxidation, triglyceride clearance, lipoprotein production, and cholesterol homeostasis.
PPAR-alpha is a type II nuclear receptor (its subcellular location does not depend on ligand binding). PPAR-alpha forms heterodimers with Retinoid X receptor alpha (RXR-alpha), another type II nuclear receptor. PPAR-alpha is activated by binding fatty acid ligands, especially polyunsaturated fatty acids having 18-22 carbon groups and 2-6 double bonds.
The PPAR-alpha:RXR-alpha heterodimer binds peroxisome proliferator receptor elements (PPREs) in and around target genes. Binding of fatty acids and synthetic ligands causes a conformational change in PPAR-alpha such that it releases the corepressors and binds coactivators (CBP-SRC-HAT complex, ASC complex, and TRAP-Mediator complex) which initiate transcription of the target genes.
Target genes of PPAR-alpha participate in fatty acid transport, fatty acid oxidation, triglyceride clearance, lipoprotein production, and cholesterol homeostasis.
所含基因
19 个基因