CHYLOMICRON-SPECIFIC ENHANCEMENT OF ACYLATION STIMULATING PROTEIN ANDPRECURSOR PROTEIN C3 PRODUCTION IN DIFFERENTIATED HUMAN ADIPOCYTES

Acylation stimulating protein (ASP) is a potent stimulator of adipocyt e triacylglycerol storage. In vivo studies have shown that ASP product ion by adipocytes increases locally after a fat meal. Initial. in vitr o studies demonstrated increased production of ASP in the presence of chylomicrons (CHYLO). The present aim was to define the CHYLO componen t responsible. None of the apoproteins tested (AT, AII, AIV, CI, CII, CIII, and E) were capable of stimulating C3 (the precursor protein) or ASP production. Rather, the active component is a nonlipid, loosely a ssociated, trypsin-sensitive molecule. High pressure liquid chromatogr aphy fractionation of the CHYLO infranate proteins identified the crit ical protein as transthyretin (TTR), which binds retinol-binding prote in and complexes thyroxine and retinol. Addition of TTR alone, with li pid emulsion, or with respun CHYLO to human differentiated adipocytes had little effect on C3 and ASP production. Ey contrast, when transthy retin was added to CHYLO, C3 and ASP production were substantially enh anced up to 75- and 7.5-fold respectively, compared with the effect of native CHYLO alone. Finally, a polyclonal antibody against TTR could inhibit stimulation of C3 and ASP production by CHYLO (by 98 and 100%, respectively) and by CHYLO infranate proteins (by 99 and 94%, respect ively). We hypothesize that TTR. mediates the transfer of the active c omponents from CHYLO to adipocytes, which then stimulates increased C3 and ASP production. Thus the CHYLO provides the physiologic trigger o f the ASP pathway.