Lysosomal Acid Lipase in Lipid Metabolism and Beyond

被引：108

作者：

Li, Fang ^{[1
]}

Zhang, Hanrui ^{[1
]}

机构：

[1] Columbia Univ, Irving Med Ctr, Dept Med, Cardiometabol Genom Program,Div Cardiol, 630 W 168th St,P&S10-401, New York, NY 10032 USA

来源：

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY | 2019年 / 39卷 / 05期

基金：

美国国家卫生研究院;

关键词：

atherosclerosis; fatty acids; lipase; lipids; macrophages; GENOME-WIDE ASSOCIATION; ESTER STORAGE DISEASE; CHOLESTERYL ESTER; SUPPRESSOR-CELLS; MTOR PATHWAY; EXPRESSION; INFLAMMATION; GENE; PURIFICATION; METASTASIS;

D O I：

10.1161/ATVBAHA.119.312136

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：850 / 856

页数：7

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