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The Role of Metabolic Lipases in the Pathogenesis and Management of Liver Disease
Author(s) -
Tardelli Matteo,
Bruschi Francesca Virginia,
Trauner Michael
Publication year - 2020
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.31250
Subject(s) - lipotoxicity , lipid droplet , endoplasmic reticulum , intracellular , lipid metabolism , microbiology and biotechnology , autophagy , context (archaeology) , biology , lipid signaling , catabolism , pathogenesis , biochemistry , metabolism , enzyme , endocrinology , apoptosis , immunology , insulin resistance , paleontology , insulin
Intracellular lipolysis is an enzymatic pathway responsible for the catabolism of triglycerides (TGs) that is complemented by lipophagy as the autophagic breakdown of lipid droplets. The hydrolytic cleavage of TGs generates free fatty acids (FFAs), which can serve as energy substrates, precursors for lipid synthesis, and mediators in cell signaling. Despite the fundamental and physiological importance of FFAs, an oversupply can trigger lipotoxicity with impaired membrane function, endoplasmic reticulum stress, mitochondrial dysfunction, cell death, and inflammation. Conversely, impaired release of FFAs and other lipid mediators can also disrupt key cellular signaling functions that regulate metabolism and inflammatory processes. This review will focus on specific functions of intracellular lipases in lipid partitioning, covering basic and translational findings in the context of liver disease. In addition, the clinical relevance of genetic mutations in human disease and potential therapeutic opportunities will be discussed.