Format

Send to

Choose Destination
Arterioscler Thromb Vasc Biol. 2019 May;39(5):850-856. doi: 10.1161/ATVBAHA.119.312136.

Lysosomal Acid Lipase in Lipid Metabolism and Beyond.

Author information

1
From the Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York.

Abstract

Lysosomal acid lipase (LAL), encoded by the lipase A ( LIPA) gene, hydrolyzes cholesteryl esters and triglycerides to generate free fatty acids and cholesterol in the cell. The essential role of LAL in lipid metabolism has been confirmed in mice and human with LAL deficiency. In humans, loss-of-function mutations of LIPA cause rare lysosomal disorders, Wolman disease and cholesteryl ester storage disease, in which LAL enzyme-replacement therapy has shown significant benefits in a phase 3 clinical trial. Recent studies have revealed the regulatory role of lipolytic products of lysosomal lipid hydrolysis in catabolic, anabolic, and signaling pathways. In vivo studies in mice with knockout of Lipa highlight the systemic impact of Lipa deficiency on metabolic homeostasis and immune cell function. Genome-wide association studies and functional genomic studies have identified LIPA as a risk locus for coronary heart disease, but the causal variants and mechanisms remain to be determined. Future studies will continue to focus on the role of LAL in the crosstalk between lipid metabolism and cellular function in health and diseases including coronary heart disease.

KEYWORDS:

atherosclerosis; fatty acids; lipase; lipids; macrophages

PMID:
30866656
PMCID:
PMC6482091
[Available on 2020-05-01]
DOI:
10.1161/ATVBAHA.119.312136

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center