Abstracts Biological Sciences

Acylation stimulating protein (ASP) structure & function studies : in vitro and in vivo in mouse models

by Ian V. J. Murray

Acylation stimulating protein (ASP or C3a desArg) is a complement derived product produced by adipocytes and is able to alter their metabolism, stimulating both triglyceride synthesis and glucose transport. This stimulatory activity has been shown to be due to ASP as both plasma derived protein and recombinant protein stimulate glucose transport and triglyceride synthesis. Furthermore, we demonstrated that ASP is functionally distinct from C3a. A two site model for ligand interaction with the receptor is proposed with the carboxy-terminal involved in receptor binding and the disulphide core in stimulating triglyceride synthesis. Functionality of ASP in vivo supported the hypothesis that ASP is involved in plasma triglyceride and glucose clearance postprandially after a fat load. The following data were obtained: (1) Administration of ASP and ASP functional knockouts displayed increased and delayed triglyceride clearance respectively. (2) Administered ASP decreased plasma glucose levels, which was independent from its effects on plasma triglycerides. (3) In ASP functional knockout mice gender differences of greater postprandial lipemia in males and more pronounced reductions of adipose tissue in females were observed. In conclusion the function of ASP was determined as well as structural regions involved. Furthermore, the in vivo physiology of ASP has been determined, with an effect on postprandial metabolism, regulation of adiposity and gender dependent penetrance of the ASP functional knockout phenotype.