Lipid and lipoprotein analysis of cats with lipoprotein lipase deficiency

Background We have previously described a colony of domestic cats with a na turally occurring mutation in the lipoprotein lipase (LBL) gene. We have no w further characterized cats homozygous for LPL deficiency (LPL -/-, homozy gotes), and have contrasted these with heterozygotes (LPL +/-) and normal c ats (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 l oading studies and breast milk fatty acid analysis were also performed to f urther characterize the phenotypic expression of LPL deficiency in this mod el system. Results Several lipid abnormalities associated with homozygosity for LPL de ficiency 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 mm oI 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 (HDLC, 1.75 +/- 0.24 vs. 1.41 +/- 0.14 mmol L-1, P < 0.05). LDL-C levels were lower in hom ozygous cats than in control cats, similar to what is seen in human LPL def iciency. Oral far loading studies revealed that homozygous cats have a mark ed 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 (AU C, 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 heterozygou s and normal cats. However, oral fat loading in heterozygotes revealed an i ntermediate 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 lipoprote in phenotype that predominantly parallels human LPL deficiency, further val idating the use of these animals in studies on the pathobiology of LPL.