4.8 Review

Lipolysis: cellular mechanisms for lipid mobilization from fat stores

Journal

NATURE METABOLISM
Volume 3, Issue 11, Pages 1445-1465

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s42255-021-00493-6

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This review discusses the significant revisions in the understanding of intracellular lipolysis over the past two decades, focusing on how it affects lipid-mediated signaling, metabolic regulation, and energy homeostasis in multiple organs. The review also explores how these processes impact disease pathogenesis and how targeting lipolysis could potentially prevent or treat various diseases.
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. Zechner and colleagues discuss mechanisms facilitating the mobilization of intracellular fatty acids and how they affect lipid-mediated signalling, metabolic regulation and energy homeostasis in health and disease.

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