Background

In vitro studies have shown that acylation stimulating protein (ASP) stimulates triglyceride (TG) synthesis and storage in adipocytes. We have previously demonstrated that intraperitoneal (i.p.) injection of ASP in C57BL/6J mice accelerated TG clearance following an orally-administered fat load as well as reducing postprandial glucose levels.

Results

In the present study, we first examined the effect of i.p. and intracerebroventricular (i.c.v.) injection of ASP on food intake in Sprague-Dawley rats. Intraperitoneal injection resulted in a short-term increase in food intake (maximum increase 29.3% within the first hour, P<0.025) decreasing thereafter as compared to vehicle alone. i.c.v. Administration of a comparable dose of ASP resulted in a similar but delayed increase in food intake with a maximum at 2-4 h, suggesting that the actions of ASP are peripherally mediated. However, there was no significant difference in 24 h food intake with either i.p. or i.c.v. injection. We also examined the effects of ASP on TG clearance in two obese mouse strains with different metabolic profiles: ob/ob (C57BL/6J-Lep(ob)) and db/db (C57BLKS/J-Lepr(db)). In a crossover design, the response to an oral fat load was determined with and without i.p. injection of exogenous ASP. In ob/ob mice, there was a 44% greater clearance of postprandial TG (area under the curve (AUC)=245+/-49 control vs 138+/-43 mg/dl h with ASP; P<0.05 by RM ANOVA). The db/db mice showed a greater response, with a 62% decrease in postprandial TG (AUC=4080+/-1489 control vs 1540+/-719 mg/dl h with ASP; P=0.004 by RM ANOVA). In addition there were decreases in postprandial glucose and non-esterified fatty acid (NEFA) levels in response to ASP.

Conclusion

These results are the first to report that ASP can increase food intake in rats and also enhance postprandial TG clearance in obese animals. These data therefore support previous in vitro evidence pointing to ASP as a regulator of lipid metabolism.