PLASMA ACYLATION STIMULATING PROTEIN (ASP) AS A PREDICTOR OF IMPAIREDCELLULAR BIOLOGICAL RESPONSE TO ASP IN PATIENTS WITH HYPERAPOB

Background The objective of this study was to examine specific membran e binding of [I-125]-acylation stimulating protein (ASP) in cultured h uman skin fibroblasts obtained from normal subjects and patients with hyperapoB. ASP is a small basic protein isolated from human plasma tha t stimulates triglyceride synthesis (TGS) and glucose transport (GT) i n human skin fibroblasts and adipocytes. Design In the present study, three groups were studied: normal (N-ASP-N-B) subjects, hyperapoB subj ects with normal plasma ASP (N-ASP-H-B) and hyperapoB subjects with hi gh plasma ASP (H-ASP-H-B) Results ASP-induced TGS in fibroblasts from H-ASP-H-B subjects was significantly less than in the two control grou ps with normal plasma ASP (N-ASP-N-B and N-ASP-H-B) Similarly, ASP sti mulation of GT was less in H-ASP-H-B fibroblasts than in the N-ASP-H-B fibroblasts or the N-ASP-N-B subjects. Insulin-induced TGS was simila r in all three groups as was insulin-stimulated GT. As well, protein k inase C-mediated stimulation was equivalent among the three groups bot h for GT and for TGS. There was no significant difference in the bindi ng affinity (Kd) Of [I-125]-ASP to intact cells in any group. By contr ast, binding of [I-125]-ASP revealed a significantly lower B-max of th e H-ASP-H-B cell lines than the N-ASP-N-B cells and the N-ASP-H-B cell s. Conclusion A decrease in the ASP cell-surface receptor concentratio n is responsible for decreased ASP stimulation of TGS, and GT and may contribute to the inefficient postprandial triglyceride (TG) clearance in H-ASP-H-B subjects.