Lipid and lipoprotein analysis of cats with lipoprotein lipase deficiency

• Published in: European journal of clinical investigation Vol. 29; no. 1; pp. 17 - 26
• Main Authors: GINZINGER, D. G, CLEE, S. M, INNIS, S, JONES, B, FRUCHART, J.-C, HAYDEN, M. R, DALLONGEVILLE, J, LEWIS, M. E. S, HENDERSON, H. E, BAUJE, E, ROGERS, Q. R, JENSEN, D. R, ECKEL, R. H, DYER, R
• Format: Journal Article
• Language: English
• Published: Oxford BSL Blackwell Science Ltd 01.01.1999; Blackwell; Blackwell Publishing Ltd
• Subjects: Animals; Biological and medical sciences; Blood Chemical Analysis; Cats; Cats - genetics; Cats - metabolism; Cholesterol - blood; Dietary Fats - metabolism; Disorders of blood lipids. Hyperlipoproteinemia; Fatty Acids - analysis; Female; Heterozygote; Homozygote; Lactation; Lipids - analysis; lipoprotein lipase; Lipoprotein Lipase - deficiency; Lipoprotein Lipase - genetics; lipoproteins; Lipoproteins - blood; Male; Medical sciences; Metabolic diseases; Milk - chemistry; milk fatty acids; Mutation; oral fat load; particle composition; Particle Size; Postprandial Period; Triglycerides - blood; Fissipedia; Animal model; Carnivora; Pathophysiology; Enzyme; Deficiency; Metabolic diseases; Lipids; Esterases; Lipoprotein lipase; Lipoprotein; Enzymopathy; Congenital disease; Carboxylic ester hydrolases; Vertebrata; Mammalia; Animal; Cat; Hydrolases
• DOI: 10.1046/j.1365-2362.1999.00435.x
• ISSN: 0014-2972

Background We have previously described a colony of domestic cats with a naturally occurring mutation in the lipoprotein lipase (LPL) gene. We have now further characterized cats homozygous for LPL deficiency (LPL −/−, homozygotes), and have contrasted these with heterozygotes (LPL +/−) and normal cats (LPL +/+). Materials and methods Density gradient ultracentrifugation with subsequent lipid analysis, agarose and polyacrylamide gel electrophoresis was used to examine detailed liproprotein differences between the genotypes. Oral fat loading studies and breast milk fatty acid analysis were also performed to further characterize the phenotypic expression of LPL deficiency in this model system. Results Several lipid abnormalities associated with homozygosity for LPL deficiency were evident. Triglyceride‐rich lipoprotein‐triglycerides (TRL‐TG) and cholesterol (TRL‐C) were higher (TRL‐TG 2.09 ± 1.14 vs. 0.15 ± 0.04 mmol L−1, P < 0.001; TRL‐C 0.42 ± 0.30 vs. 0.11 ± 0.16 mmol L−1, P < 0.05) in male −/− than in male +/+ cats, as was HDL‐cholesterol (HDL‐C, 1.75 ± 0.24 vs. 1.41 ± 0.14 mmol L−1, P < 0.05). LDL‐C levels were lower in homozygous cats than in control cats, similar to what is seen in human LPL deficiency. Oral fat loading studies revealed that homozygous cats have a marked reduced ability to clear plasma TGs in terms of peak time (7 h vs. 3 h), peak height (9.36 vs. 1.1 mmol L−1), area under the TG clearance curve (AUC, 280.3 vs. 2.2 h mmol L−1) and time to return to baseline. Fasting lipid and lipoprotein levels were not significantly different between heterozygous and normal cats. However, oral fat loading in heterozygotes revealed an intermediate phenotype (peak of 2.35 mmol L−1 at 5 h, AUC 13.1 h mmol L−1), highlighting the impaired TG clearance in these animals. Conclusion Thus, LPL deficiency in the cat results in a lipid and lipoprotein phenotype that predominantly parallels human LPL deficiency, further validating the use of these animals in studies on the pathobiology of LPL.