Effects of dietary cholesterol restriction in a feline model of Niemann–Pick type C disease

• Published in: Journal of inherited metabolic disease Vol. 24; no. 4; pp. 427 - 436
• Main Authors: Somers, K. L., Brown, D. E., Fulton, R., Schultheiss, P. C., Hamar, D., Smith, M. O., Allison, R., Connally, H. E., Just, C., Mitchell, T. W., Wenger, D. A., Thrall, M. A.
• Format: Journal Article
• Language: English
• Published: Dordrecht Kluwer Academic Publishers 01-07-2001; Springer; Blackwell Publishing Ltd
• Subjects: Alanine Transaminase - blood; Alkaline Phosphatase - blood; Animals; Bilirubin - blood; Biological and medical sciences; Cats; Cholesterol - blood; Cholesterol, Dietary - administration & dosage; Cytoplasm - ultrastructure; Disease Models, Animal; Errors of metabolism; Lipids (lysosomal enzyme disorders, storage diseases); Lipids - analysis; Liver - chemistry; Liver - ultrastructure; Medical sciences; Metabolic diseases; Niemann-Pick Diseases - diet therapy; Niemann-Pick Diseases - pathology; Niemann-Pick Diseases - physiopathology; Serum Albumin - analysis; Vacuoles - pathology; Fissipedia; Animal model; Carnivora; Nervous system diseases; Treatment efficiency; Liver; Metabolic diseases; Lipids; Type C; Enzymopathy; Cholesterol; Cerebral disorder; Genetic disease; Pathology; Vertebrata; Mammalia; Diet therapy; Central nervous system disease; Cat; Niemann Pick disease; Restricted diet; Lipoidosis
• ISSN: 0141-8955; 1573-2665
• DOI: 10.1023/A:1010588112003

A feline model of Niemann–Pick disease type C (NPC) was employed to evaluate the effect of dietary cholesterol restriction on progression of disease. Two NPC‐affected treated cats were fed a cholesterol‐restricted diet beginning at 8 weeks of age; the cats remained on the diet for 150 and 270 days respectively. The study goal was to lower the amount of low density lipoprotein (LDL) available to cells, hypothetically reducing subsequent lysosomal accumulation of unesterified cholesterol and other lipids. Neurological progression of disease was not altered and dietary cholesterol restriction did not significantly decrease storage in NPC‐affected treated cats. One NPC‐affected treated cat had decreased serum alkaline phosphatase activity (ALP) and decreased serum cholesterol concentration. Liver lipid concentrations of unesterified cholesterol, cholesterol ester and phospholipids in NPC‐affected treated cats were similar to those seen in NPC‐affected untreated cats. Ganglioside concentrations in the NPC‐affected treated cats and NPC‐affected untreated cats were similar. Histological findings in liver sections from NPC‐affected treated cats showed a diffuse uniform microvacuolar pattern within hepatocytes and Kupffer cells, in contrast to a heterogeneous macro/microvacuolar pattern and prominent nodular fibrosis in NPC‐affected untreated cats. Similar differences in vacuolar patterns were seen in splenic macrophages. Although some hepatic parameters were modified, dietary cholesterol restriction did not appear to alter disease progression in NPC‐affected kittens.