A critical evaluation of the putative role of C3adesArg (ASP) in lipid metabolism and hyperapobetalipoproteinemia.
The acylation stimulating protein, ASP is a small, basic serum protein capable of stimulating triglyceride synthesis in cultured fibroblasts and adipocytes. Sequence analysis of ASP has shown that ASP is identical to C3adesArg the inactive fragment of the complement anaphylatoxin peptide, C3a. It has been proposed that C3adesArg (ASP) can be generated by mature adipocytes secreting the three complement proteins: complement protein C3, factor B and factor D (adipsin). There have also been indications that adipocytes may express a specific C3adesArg (ASP)-receptor that is distinct from the recently cloned C3a-receptor. This suggests that C3adesArg (ASP) acts as an adipocyte autocrine and that it plays a central role in the metabolism of adipose tissue. Based on these observations a hypothesis for the etiology of hyperapobetalipoproteinemia (hyperapoB) has been proposed. Hyperapobetalipoproteinemia (hyperapoB), is a familial lipoprotein disorder characterized by increased hepatic secretion of very low density lipoprotein (VLDL) and low density lipoprotein (LDL) particles. If C3adesArg (ASP) function in the adipose tissue is impaired, a reduced rate of triglyceride synthesis will follow, generating an increased flux of fatty acids to the liver. In response to an increased flow of fatty acids, the liver will increase its production of VLDL particles yielding the phenotype of hyperapoB. This review critically assesses this hypothesis and the potential role of C3adesArg (ASP) as a major determinant for triglyceride synthesis in the light of data collected in vitro and in vivo.
Kildsgaard
J
J
University of Texas-Houston Institute of Molecular Medicine for Prevention of Human Diseases, 77030, USA.
Zsigmond
E
E
Chan
L
L
Wetsel
R A
RA
D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism; D003176:Complement C3 / Q000172:deficiency / Q000378:metabolism; D015926:Complement C3a / Q000031:analogs & derivatives* / Q000378:metabolism; D011416:Complement Factor D; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000209:etiology / Q000378:metabolism*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008954:Models, Biological; D011951:Receptors, Complement / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D014280:Triglycerides / Q000096:biosynthesis
D001055:Apolipoproteins B; D003176:Complement C3; D008565:Membrane Proteins; D011951:Receptors, Complement; D014280:Triglycerides; C085567:complement C3a receptor; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a; D012697:Serine Endopeptidases; C493488:CFD protein, human; D011416:Complement Factor D; C493491:complement factor D, mouse