The loss of lysosomal acid lipase (LAL) in enterocytes is not sufficient to cause per se lipid deposition in the small intestine, a common finding in lysosomal acid lipase deficiency (LAL-D), according to researchers from the Medical University of Graz, Austria.

To investigate what happens to lipid metabolism and absorption in conditions of whole-body and intestinal LAL-D, the researchers used 2 knockout (KO) mice models to mimic global and intestine-specific deletion of LAL conditions (LAL-D KO and iLAL-D KO, respectively). Wild-type mice were used as controls.

“Although small intestinal LAL expression and lipid accumulation are substantial in LAL KO mice, iLAL KO animals do not recapitulate this phenotype,” the researchers explained.

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LAL-D KO and iLAL-D KO mice showed different phenotypes. LAL-D KO mice had substantial lipid accumulation in the small intestine, particularly in lamina propria macrophages. This finding was associated with increased cholesterol absorption.

On the other hand, iLAL KO mice had normal villus morphology and lipid concentrations in spite of reduced LAL activity in enterocytes. Moreover, the expression of lipid transporters and inflammatory genes was not altered in the small intestines of the iLAL KO mice.

Read more about LAL-D etiology

The researchers isolated duodenum, jejunum, ileum, and liver specimens from each mouse model to analyze ribonucleic acid (RNA), proteins, and lipids, as well as lipoprotein secretion and cholesterol absorption.

In humans, LAL-D is caused by loss-of-function mutations in the LIPA gene. Disease severity depends on the level of residual activity of the mutant LAL.

Additional studies should clarify the role of LAL in enterocytes and further characterize the involvement of macrophages in intestinal lipid deposition, the researchers wrote.


Bianco V, Korbelius M, Vujic N, Akhmetshina A, Kolb D, Kratky D. Consequences of (intestinal) LAL deficiency on whole body lipid metabolism. Atherosclerosis. 2022;355:10. doi:10.1016/j.atherosclerosis.2022.06.116