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- Title
Modulation of Dietary Choline Uptake in a Mouse Model of Acid Sphingomyelinase Deficiency.
- Authors
Gaudioso, Ángel; Moreno-Huguet, Pilar; Casas, Josefina; Schuchman, Edward H.; Ledesma, María Dolores
- Abstract
Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disorder caused by mutations in the gene-encoding acid sphingomyelinase (ASM). ASMD impacts peripheral organs in all patients, including the liver and spleen. The infantile and chronic neurovisceral forms of the disease also lead to neuroinflammation and neurodegeneration for which there is no effective treatment. Cellular accumulation of sphingomyelin (SM) is a pathological hallmark in all tissues. SM is the only sphingolipid comprised of a phosphocholine group linked to ceramide. Choline is an essential nutrient that must be obtained from the diet and its deficiency promotes fatty liver disease in a process dependent on ASM activity. We thus hypothesized that choline deprivation could reduce SM production and have beneficial effects in ASMD. Using acid sphingomyelinase knock-out (ASMko) mice, which mimic neurovisceral ASMD, we have assessed the safety of a choline-free diet and its effects on liver and brain pathological features such as altered sphingolipid and glycerophospholipid composition, inflammation and neurodegeneration. We found that the choline-free diet was safe in our experimental conditions and reduced activation of macrophages and microglia in the liver and brain, respectively. However, there was no significant impact on sphingolipid levels and neurodegeneration was not prevented, arguing against the potential of this nutritional strategy to assist in the management of neurovisceral ASMD patients.
- Subjects
NIEMANN-Pick diseases; CHOLINE; LABORATORY mice; FATTY liver; ANIMAL disease models; LYSOSOMES
- Publication
International Journal of Molecular Sciences, 2023, Vol 24, Issue 11, p9756
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms24119756