Abstract
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.
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Acknowledgements
R. Z. and M. S. are supported by grants from the FWF SFB Lipid Hydrolysis (grant number F7302) and SFB Immunometabolism (grant number F83), respectively. R. Z. is additionally supported by the Louis Jeantet Prize 2015 awarded by the Louis Jeantet Foundation.
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Conceptualization was done by M. S. and R. Z.; G. F. G., H. X., M. S. and R. Z. wrote the manuscript; figures were prepared by G. F. G. and M. S.
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Grabner, G.F., Xie, H., Schweiger, M. et al. Lipolysis: cellular mechanisms for lipid mobilization from fat stores. Nat Metab 3, 1445–1465 (2021). https://doi.org/10.1038/s42255-021-00493-6
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DOI: https://doi.org/10.1038/s42255-021-00493-6
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