Genetic deficiency of acylation stimulating protein (ASP(C3ades-Arg)) does not cause hyperapobetalipoproteinemia in mice.
The acylation stimulating protein (ASP) is a 76-amino acid peptide that has been proposed as a potent mediator of triglyceride synthesis and, when functionally impaired, as a major cause of hyperapobetalipoproteinemia (HyperapoB). Purification and sequence analysis of ASP from human sera have revealed that ASP is identical to the complement C3-derived activation peptide C3ades-Arg. Because C3 is the precursor for C3ades-Arg and therefore ASP, a deficiency in C3 would be predicted to result in a phenotype characteristic of HyperapoB. To test this hypothesis in vivo, the current study was undertaken in which ASP(C3ades-Arg)-deficient mice were used as a model system. No significant differences were found in the triglyceride, cholesterol, or free fatty acid concentrations in the plasma of fasted normal and ASP(C3ades-Arg)-deficient animals. In addition, plasma lipoprotein analyses indicated that the very low density lipoprotein, low density lipoprotein, and high density lipoprotein cholesterol and triglyceride concentrations as well as the apolipoprotein B-48 and B-100 levels were not significantly different in the plasma of ASP(C3ades-Arg)-deficient and wild type mice. Furthermore, when challenged with an oral fat load, the ASP(C3ades-Arg)-deficient mice showed no impaired ability to clear triglycerides and free fatty acids from their circulation when compared with their wild-type littermates. Collectively, these results indicate that ASP(C3ades-Arg) deficiency does not cause HyperapoB in mice and that the physiological importance of impaired ASP(C3ades-Arg) function as a cause of hyperapobetalipoproteinemia needs to be reevaluated.
Wetsel
R A
RA
Institute of Molecular Medicine for the Prevention of Human Diseases, Houston Texas 77030, USA. rwetsel@imm2.imm.uth.tmc.edu
Kildsgaard
J
J
Zsigmond
E
E
Liao
W
W
Chan
L
L
D000818:Animals; D001055:Apolipoproteins B / Q000097:blood / Q000235:genetics*; D001798:Blood Proteins / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D015926:Complement C3a / Q000031:analogs & derivatives*; D004041:Dietary Fats / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006801:Humans; D006951:Hyperlipoproteinemias / Q000097:blood / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D014280:Triglycerides / Q000097:blood
D001055:Apolipoproteins B; D001798:Blood Proteins; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D014280:Triglycerides; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a; D002784:Cholesterol