Lysosomal acid lipase (LAL) hydrolyzes cholesteryl esters (CEs) and triglycerides (TGs) to free cholesterol (FC) and free fatty acids (FFAs), which are then used for metabolic purposes in the cell. The process also occurs in immune cells that adapt their metabolic machinery to cope with the different energetic requirements associated with cell activation, proliferation, and polarization. LAL deficiency (LALD) causes severe lipid accumulation and affects the immunometabolic signature in animal models. In humans, LAL deficiency is associated with a peculiar clinical immune phenotype, secondary hemophagocytic lymphohistiocytosis. These observations suggest that LAL might play an important role in cellular immunometabolic modulation, and availability of an effective enzyme replacement strategy makes LAL an attractive target to rewire the metabolic machinery of immune cells beyond its role in controlling cellular lipid metabolism.

Lysosomal Acid Lipase: From Cellular Lipid Handler to Immunometabolic Target / M. Gomaraschi, F. Bonacina, G.D. Norata. - In: TRENDS IN PHARMACOLOGICAL SCIENCES. - ISSN 0165-6147. - 40:2(2019 Feb), pp. 104-115. [10.1016/j.tips.2018.12.006]

Lysosomal Acid Lipase: From Cellular Lipid Handler to Immunometabolic Target

M. Gomaraschi
Primo
;
F. Bonacina
Secondo
;
G.D. Norata
Ultimo
2019-02

Abstract

Lysosomal acid lipase (LAL) hydrolyzes cholesteryl esters (CEs) and triglycerides (TGs) to free cholesterol (FC) and free fatty acids (FFAs), which are then used for metabolic purposes in the cell. The process also occurs in immune cells that adapt their metabolic machinery to cope with the different energetic requirements associated with cell activation, proliferation, and polarization. LAL deficiency (LALD) causes severe lipid accumulation and affects the immunometabolic signature in animal models. In humans, LAL deficiency is associated with a peculiar clinical immune phenotype, secondary hemophagocytic lymphohistiocytosis. These observations suggest that LAL might play an important role in cellular immunometabolic modulation, and availability of an effective enzyme replacement strategy makes LAL an attractive target to rewire the metabolic machinery of immune cells beyond its role in controlling cellular lipid metabolism.
cholesterol; enzyme replacement therapy; fatty acids; immune response; lysosomal acid lipase; Toxicology; Pharmacology
Settore BIO/14 - Farmacologia
Proprotein convertase subtilisin/kexin type 9 (PCSK9): a link between lipotoxicity, mitochondrial dysfunction, and frailty-associated heart failure
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/614914
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