Peroxisome proliferator-activated receptors (PPARs) constitute a small family of three nuclear receptors that act as lipid sensors, and thereby regulate the transcription of genes having key roles in hepatic and whole-body energy homeostasis, and in other processes (e.g., inflammation), which have far-reaching health consequences. Peroxisome proliferator-activated receptor isotype α (PPARα) is expressed in oxidative tissues, particularly in the liver, carrying out critical functions during the adaptive fasting response. Advanced omics technologies have provided insight into the vast complexity of the regulation of PPAR expression and activity, as well as their downstream effects on the physiology of the liver and its associated metabolic organs. Here, we provide an overview of the gene regulatory networks controlled by PPARα in the liver in response to fasting. We discuss impacts on liver metabolism, the systemic repercussions and benefits of PPARα-regulated ketogenesis and production of fibroblast growth factor 21 (FGF21), a fasting- and stress-inducible metabolic hormone. We also highlight current challenges in using novel methods to further improve our knowledge of PPARα in health and disease.

中文翻译：

---

PPARα 脂质感应：在控制肝细胞基因调控网络和对空腹的代谢反应中的作用


过氧化物酶体增殖物激活受体 （PPAR） 构成了一个由三个核受体组成的小家族，它们充当脂质传感器，从而调节在肝脏和全身能量稳态以及其他过程（例如炎症）中起关键作用的基因的转录，这对健康具有深远的影响。过氧化物酶体增殖物激活受体同种型 α （PPARα） 在氧化组织中表达，特别是在肝脏中，在适应性禁食反应期间执行关键功能。先进的组学技术为了解 PPAR 表达和活性调节的巨大复杂性，以及它们对肝脏及其相关代谢器官生理学的下游影响提供了见解。在这里，我们概述了肝脏中 PPARα 响应禁食而控制的基因调控网络。我们讨论了对肝脏代谢的影响、PPARα 调节的生酮作用和成纤维细胞生长因子 21 （FGF21） 的产生（一种空腹和应激诱导的代谢激素）的产生。我们还强调了当前使用新方法进一步提高我们对健康和疾病中 PPARα 的了解所面临的挑战。