Laboratoire de Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique (Bio-PeroxIL, EA 7270), Université de Bourgogne, Dijon F-21000, France.
Curr Drug Metab. 2012 Dec;13(10):1412-21. doi: 10.2174/138920012803762765.
Three subhepatocellular compartments concur for fatty acids degradation including ω-oxidation in endoplasmic reticulum and β-oxidation in both mitochondria and peroxisomes. Deficits affecting the peroxisomal physiology may be associated with multiple metabolic disturbances. Nowadays, a growing body of evidence underlines the key role of peroxisomal β-oxidation in the sensing of lipid metabolism through the production/degradation of some essential metabolites. Lessons from several mice models strengthen the link between fatty acid β-oxidation in peroxisomes and the nuclear hormone receptor Peroxisome Proliferator-Activated Receptor (PPAR)-α with an additional level of coregualtor complexity, which couples regulation of body energetic balance and hepatic caloric flux to functional peroxisome status. Here, we review key determinants of disrupted peroxisomal β-oxidation pathway, which in liver promotes hepatic steatosis and hepatocarcinogenesis.
三个亚肝细胞区室共同参与脂肪酸降解，包括内质网中的 ω-氧化和线粒体及过氧化物酶体中的 β-氧化。影响过氧化物体生理学的缺陷可能与多种代谢紊乱有关。如今，越来越多的证据强调了过氧化物体β-氧化在通过某些必需代谢物的产生/降解来感知脂质代谢中的关键作用。来自几种小鼠模型的经验教训加强了过氧化物体中脂肪酸β-氧化与核激素受体过氧化物酶体增殖物激活受体 (PPAR)-α 之间的联系，以及核心调节剂复杂性的附加水平，该水平将身体能量平衡和肝热量通量的调节与功能性过氧化物体状态联系起来。在这里，我们回顾了破坏过氧化物体β-氧化途径的关键决定因素，该途径在肝脏中促进肝脂肪变性和肝癌发生。
