Institute of Molecular Biosciences, University of Graz, Graz, Austria.
BioTechMed-Graz, Graz, Austria.
Nat Metab. 2021 Nov;3(11):1445-1465. doi: 10.1038/s42255-021-00493-6. Epub 2021 Nov 19.
The perception that intracellular lipolysis is a straightforward process that releases fatty acids from fat stores in adipose tissue to generate energy has experienced major revisions over the last two decades. The discovery of new lipolytic enzymes and coregulators, the demonstration that lipophagy and lysosomal lipolysis contribute to the degradation of cellular lipid stores and the characterization of numerous factors and signalling pathways that regulate lipid hydrolysis on transcriptional and post-transcriptional levels have revolutionized our understanding of lipolysis. In this review, we focus on the mechanisms that facilitate intracellular fatty-acid mobilization, drawing on canonical and noncanonical enzymatic pathways. We summarize how intracellular lipolysis affects lipid-mediated signalling, metabolic regulation and energy homeostasis in multiple organs. Finally, we examine how these processes affect pathogenesis and how lipolysis may be targeted to potentially prevent or treat various diseases.
在过去的二十年中,人们对内质网脂解是一个简单的过程,能够从脂肪组织中的脂肪储存中释放脂肪酸以产生能量的观点进行了重大修正。新的脂解酶和共调节剂的发现、脂噬作用和溶酶体脂解有助于细胞脂质储存降解的证明、以及许多调节转录和转录后水平脂肪水解的因素和信号通路的特征,彻底改变了我们对内质网脂解的理解。在这篇综述中,我们重点讨论了促进细胞内脂肪酸动员的机制,借鉴了经典和非经典的酶促途径。我们总结了细胞内脂解如何影响多种器官中的脂介信号转导、代谢调节和能量稳态。最后,我们研究了这些过程如何影响发病机制以及如何靶向脂解以潜在地预防或治疗各种疾病。