Researchers have proposed that lysosomal acid lipase deficiency (LAL-D) may contribute to the development of atherosclerosis and fatty liver disease, according to a review article published in Frontiers in Genetics.
Lysosomal acid lipase (LAL) plays an important role in the hydrolysis of cholesteryl esters. In addition, it cleaves stored cholesteryl esters delivered to lysosomes for lipophagy.
The authors of the review pointed out that scientists have suggested that low LAL might result in the accumulation of cholesteryl esters in aortic cells. Studies using mouse models revealed that defective cholesterol handling by arterial smooth muscle cells occurs in LAL-D, leading to cholesterol accumulation in atherosclerotic plaques.
In terms of liver pathology, medical literature has established the role that LAL-D plays not only in microvesicular steatosis and fatty liver disease, but also in nonalcoholic fatty liver disease (NAFLD). NAFLD has a global prevalence of around 25% and is characterized by steatosis in the liver. The most common cause of death in patients with NAFLD is cardiovascular disease, underlining how hepatic disorders can sometimes cause systemic vascular damage and coagulation.
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“The pathogenesis of the lowered LAL activity in NAFLD is as yet unknown,” Besler and colleagues wrote. “Multiple studies screening for LAL mutations in NAFLD patients with low LAL activity did not find any.”
Instead, studies suggest that NAFLD is linked to low functional levels of LAL and the abnormal accumulation of dysfunctional ubiquitinated LAL. These findings suggest that lower LAL activity is partly due to liver pathology.
“It is likely that in the next decade the activity and functions of LAL will assume an ever increasing role in our understanding of the pathogenesis and potential treatment of both atherosclerosis and fatty liver disease,” the authors of the review concluded.
Besler KJ, Blanchard V, Francis GA. Lysosomal acid lipase deficiency: a rare inherited dyslipidemia but potential ubiquitous factor in the development of atherosclerosis and fatty liver disease. Front Genet. Published online September 20, 2022. doi:10.3389/fgene.2022.1013266