Acylation stimulating protein (ASP) acute effects on postprandial lipemia and food intake in rodents

BACKGROUND: In vitro studies have shown that acylation stimulating protein (ASP) stimulates triglyceride (TC) synthesis and storage in adipocytes. We have previously demonstrated that intraperitoneal (i.p.) injection of ASP i n C57BL/6j mice accelerated TC clearance following an orally-administered f at load as well as reducing postprandial glucose levels. RESULTS: In the present study, we first examined the effect of i.p. and int racerebroventricular (i.c.v.) injection of ASP on food intake in Sprague-Da wley rats. Intraperitoneal injection resulted in a short-term increase in f ood intake (maximum increase 29.3% within the first hour, P < 0.025) decrea sing thereafter as compared to vehicle alone, i.c.v. Administration of a co mparable dose of ASP resulted in a similar but delayed increase in food int ake with a maximum at 2 - 4 h, suggesting that the actions of ASP are perip herally 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 TC clearance in two obese mouse strains with different metabolic profiles: ob/ob (C57BL/6jLep(ob)) and db/db (C57BLKS/J-Lepr(db)). In a cros sover design, the response to an oral fat load was determined with and with out 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 cont rol vs 138 +/- 43 mg/dl h with ASP; P < 0.05 by RM ANOVA). The db/db mice s howed a greater response with a 62% decrease in postprandial TC (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-esterifie d fatty acid (NEFA) levels in response to ASP. CONCLUSION: These results are the first to report that ASP can increase foo d intake in rats and also enhance postprandial TG clearance in obese animal s. These data therefore support previous in vitro evidence pointing to ASP as a regulator of lipid metabolism.