Lipa-flox Mouse

Lipa, also known as lipase A, encodes lysosomal acid lipase (LAL), which is crucial for the hydrolysis of both triglycerides (TGs) and cholesteryl esters (CEs) in the lysosome [3]. This enzyme is involved in lipid metabolism pathways, and its normal function is of great biological importance for maintaining lipid homeostasis. Genetic models, such as gene knockout models, can be used to study its function.

In Aspergillus flavus, knockout of the lipA gene led to suppressed growth, reduced formation of conidia and sclerotia, and down-regulation of aflatoxin B1 (AFB1), indicating its role in the development of A. flavus and AFB1 biosynthesis [1]. In non-alcoholic fatty liver disease (NAFLD) mouse models, exercise upregulated LIPA expression, increased its activity, and ameliorated lipid droplet metabolism disorder through the PLIN2-LIPA axis-mediated lipophagy [4]. Mutations in the LIPA gene in humans cause lysosomal acid lipase deficiency (LAL-D), with severe subtypes like Wolman disease. In Egyptian patients, novel LIPA variants were identified, expanding the spectrum of variants involved in the disease [3]. In cholesteryl ester storage disease (CESD) patients with LIPA gene mutations, there were significant changes in plasma levels and lipid composition of lipoproteins, increasing cardiovascular risk [2].

In conclusion, Lipa plays a vital role in lipid metabolism, affecting the growth and toxin production in fungi, lipid droplet metabolism in NAFLD, and lipoprotein composition in humans. The study of Lipa knockout or mutated models has enhanced our understanding of its functions in these biological processes and disease conditions, providing insights into potential therapeutic strategies for related diseases.