Genetic deficiency of acylation stimulating protein (ASP(C3ades-Arg)) doesnot 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 fun ctionally impaired, as a major cause of hyperapobetalipoproteinemia (Hypera poB), Purification and sequence analysis of ASP from human sera have reveal ed that ASP is identical to the complement C3-derived activation peptide C3 ades-Arg, Because C3 is the precursor for C3ades-Arg and therefore ASP, a d eficiency in C3 would be predicted to result in a phenotype characteristic of HyperapoB. To test this hypothesis in vivo, the current study was undert aken in which ASP(C3ades-Arg)-deficient mice were used as a model system. N o significant differences were found in the triglyceride, cholesterol, or f ree 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 d ensity lipoprotein cholesterol and triglyceride concentrations as well as t he apolipoprotein B-48 and B-100 levels were not significantly different in the plasma of ASP(C3ades-Arg)-deficient and wild type mice. Furthermore, w hen challenged with an oral fat load, the ASP(C3ades-Arg)-deficient mice sh owed no impaired ability to clear triglycerides and free fatty acids from t heir circulation when compared with their wild-type littermates, Collective ly, these results indicate that ASP(C3ades-Arg) deficiency does not cause H yperapoB in mice and that the physiological importance of impaired ASP(C3ad es-Arg) function as a cause of hyperapobetalipoproteinemia needs to be reev aluated.