Background and Aims : Lysosomal acid lipase (LAL) is the only enzyme responsible for the degradation of cholesteryl esters and triglycerides in the lysosome at an acidic pH. Mutations in its gene cause two rare autosomal recessive diseases, depending on the residual activity of the enzyme. One of the most common symptoms of LAL deficiency is lipid malabsorption throughout the small intestine accompanied by macrophage infiltration. We aim to investigate the consequences of whole-body and intestinal LAL deficiency on lipid metabolism and absorption.
Methods: We collected three parts of the small intestine (duodenum, jejunum, ileum) and livers from mice with a global (LAL KO) or intestine-specific deletion of LAL (iLAL KO) and wild-type littermates. We isolated RNA and protein and quantified lipids. Lipoprotein secretion and cholesterol absorption were also assessed.
Results: We found massive lipid accumulation in the small intestine of LAL KO mice, particularly in macrophages in the lamina propria, associated with elevated cholesterol absorption. Despite drastically reduced LAL activity in iLAL KO enterocytes, villus morphology, lipid concentrations, and expression of lipid transporters and inflammatory genes were unaltered in the small intestine of iLAL KO mice.
Conclusions: Although small intestinal LAL expression and lipid accumulation are substantial in LAL KO mice, iLAL KO animals do not recapitulate this phenotype. Therefore, loss of LAL in enterocytes alone is not sufficient to cause lipid deposition in the small intestine, implying that macrophages play an important role in this process. Further studies are needed to determine the involvement of LAL in enterocytes and macrophages in lipid absorption.
SE029 / #652 SAAG SESSION 07: CELL TALK TIME: RECEPTORS AND INTRACELLULAR TRAFFICKING 23-05-2022 1:45 PM - 2:30 PM
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