Lipid and lipoprotein analysis of cats with lipoprotein lipase deficiency

D. G. Ginzinger, S. M. Clee, J. Dallongeville, M. E.S. Lewis, H. E. Henderson, E. Bauje, Quinton Rogers, D. R. Jensen, R. H. Eckel, R. Dyer, S. Innis, B. Jones, J. C. Fruchart, M. R. Hayden

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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 mmolL-1, P < 0.001; TRL-C 0.42 ± 0.30 vs. 0.11 ± 0.16 mmolL-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 mmolL-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 mmolL-1), area under the TG clearance curve (AUC, 280.3 vs. 2.2 h mmolL-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 mmolL-1 at 5 h, AUC 13.1 h mmolL-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.

Original languageEnglish (US)
Pages (from-to)17-26
Number of pages10
JournalEuropean Journal of Clinical Investigation
Volume29
Issue number1
DOIs
StatePublished - Feb 24 1999

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Hyperlipoproteinemia Type I
Lipoprotein Lipase
Lipoproteins
Cats
Lipids
Fats
Heterozygote
Area Under Curve
Animals
Triglycerides
Phenotype
Aptitude
Agar Gel Electrophoresis
Ultracentrifugation
Homozygote
Human Milk
Electrophoresis
Sepharose
HDL Cholesterol
Polyacrylamide Gel Electrophoresis

Keywords

  • Cats
  • Lipoprotein lipase
  • Lipoproteins
  • Milk fatty acids
  • Oral fat load
  • Particle composition

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry

Cite this

Ginzinger, D. G., Clee, S. M., Dallongeville, J., Lewis, M. E. S., Henderson, H. E., Bauje, E., ... Hayden, M. R. (1999). Lipid and lipoprotein analysis of cats with lipoprotein lipase deficiency. European Journal of Clinical Investigation, 29(1), 17-26. https://doi.org/10.1046/j.1365-2362.1999.00435.x

Lipid and lipoprotein analysis of cats with lipoprotein lipase deficiency. / Ginzinger, D. G.; Clee, S. M.; Dallongeville, J.; Lewis, M. E.S.; Henderson, H. E.; Bauje, E.; Rogers, Quinton; Jensen, D. R.; Eckel, R. H.; Dyer, R.; Innis, S.; Jones, B.; Fruchart, J. C.; Hayden, M. R.

In: European Journal of Clinical Investigation, Vol. 29, No. 1, 24.02.1999, p. 17-26.

Research output: Contribution to journalArticle

Ginzinger, DG, Clee, SM, Dallongeville, J, Lewis, MES, Henderson, HE, Bauje, E, Rogers, Q, Jensen, DR, Eckel, RH, Dyer, R, Innis, S, Jones, B, Fruchart, JC & Hayden, MR 1999, 'Lipid and lipoprotein analysis of cats with lipoprotein lipase deficiency', European Journal of Clinical Investigation, vol. 29, no. 1, pp. 17-26. https://doi.org/10.1046/j.1365-2362.1999.00435.x
Ginzinger DG, Clee SM, Dallongeville J, Lewis MES, Henderson HE, Bauje E et al. Lipid and lipoprotein analysis of cats with lipoprotein lipase deficiency. European Journal of Clinical Investigation. 1999 Feb 24;29(1):17-26. https://doi.org/10.1046/j.1365-2362.1999.00435.x
Ginzinger, D. G. ; Clee, S. M. ; Dallongeville, J. ; Lewis, M. E.S. ; Henderson, H. E. ; Bauje, E. ; Rogers, Quinton ; Jensen, D. R. ; Eckel, R. H. ; Dyer, R. ; Innis, S. ; Jones, B. ; Fruchart, J. C. ; Hayden, M. R. / Lipid and lipoprotein analysis of cats with lipoprotein lipase deficiency. In: European Journal of Clinical Investigation. 1999 ; Vol. 29, No. 1. pp. 17-26.
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abstract = "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 mmolL-1, P < 0.001; TRL-C 0.42 ± 0.30 vs. 0.11 ± 0.16 mmolL-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 mmolL-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 mmolL-1), area under the TG clearance curve (AUC, 280.3 vs. 2.2 h mmolL-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 mmolL-1 at 5 h, AUC 13.1 h mmolL-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.",
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AU - Ginzinger, D. G.

AU - Clee, S. M.

AU - Dallongeville, J.

AU - Lewis, M. E.S.

AU - Henderson, H. E.

AU - Bauje, E.

AU - Rogers, Quinton

AU - Jensen, D. R.

AU - Eckel, R. H.

AU - Dyer, R.

AU - Innis, S.

AU - Jones, B.

AU - Fruchart, J. C.

AU - Hayden, M. R.

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N2 - 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 mmolL-1, P < 0.001; TRL-C 0.42 ± 0.30 vs. 0.11 ± 0.16 mmolL-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 mmolL-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 mmolL-1), area under the TG clearance curve (AUC, 280.3 vs. 2.2 h mmolL-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 mmolL-1 at 5 h, AUC 13.1 h mmolL-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.

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