Guillou Hervé, Martin Pascal G P, Pineau Thierry
Laboratoire de Pharmacologie et Toxicologie UR66, INRA, F-3100 Toulouse, France.
Subcell Biochem. 2008;49:3-47. doi: 10.1007/978-1-4020-8831-5_1.
The liver is a major site of fatty acid synthesis and degradation. Transcriptional regulation is one of several mechanisms controlling hepatic metabolism of fatty acids. Two transcription factors, namely SREBP1-c and PPARalpha, appear to be the main players controlling synthesis and degradation of fatty acids respectively. This chapter briefly presents fatty acid metabolism. The first part focuses on SREBP1-c contribution to the control of gene expression relevant to fatty acid synthesis and the main mechanisms of activation for this transcriptional program. The second part reviews the evidence for the involvement of PPARalpha in the control of fatty acid degradation and the key features of this nuclear receptor. Finally, the third part aims at summarizing recent advances in our current understanding of how these two transcription factors fit in the regulatory networks that sense hormones or nutrients, including cellular fatty acids, and govern the transcription of genes implicated in hepatic fatty acid metabolism.
肝脏是脂肪酸合成与降解的主要场所。转录调控是控制肝脏脂肪酸代谢的几种机制之一。两种转录因子,即固醇调节元件结合蛋白1c(SREBP1-c)和过氧化物酶体增殖物激活受体α(PPARα),似乎分别是控制脂肪酸合成与降解的主要因素。本章简要介绍脂肪酸代谢。第一部分重点阐述SREBP1-c在控制与脂肪酸合成相关基因表达方面的作用以及该转录程序的主要激活机制。第二部分综述PPARα参与脂肪酸降解控制的证据以及该核受体的关键特征。最后,第三部分旨在总结我们目前对这两种转录因子如何融入感知激素或营养物质(包括细胞脂肪酸)并调控参与肝脏脂肪酸代谢相关基因转录的调控网络的最新认识进展。