Albumin inhibits apolipoprotein AI and AII production in human hepatoblastoma cell line (Hep G2): additive effects of oleate-albumin complex

Although the role of multiple humoral agents (such as plasma albumin, gluco se, hormones etc.) are implicated in lipoprotein metabolism, the mechanism of action of these agents on various steps of the synthesis and secretion o f lipoproteins and apolipoproteins (protein moieties of lipoproteins) are n ot completely understood. Specifically, the hepatocellular mechanisms of th e effect of albumin and fatty acids on apolipoprotein (apo) AI and AII [maj or proteins of high density lipoproteins (HDL)] synthesis and secretion are not known. Using human hepatoblastoma cells (Hep G2) as an in vitro model system, this study examined the effect of albumin and fatty acids on the sy nthesis, secretion, and the steady-state mRNA expression of apo AI and AII. The data indicated that the incubation of Hep G2 cells with albumin, dose- dependently, inhibited apo AI and AII accumulation (secretion) in the media , de novo synthesis, and the steady-state mRNA expression. Albumin did not alter total protein synthesis; thus the effect of albumin appeared to be sp ecific for the synthesis and secretion of apo AI and apo AII. Free fatty ac ids (FFA) are transported by albumin and diseases characterized by enhanced FFA mobilization (e.g. diabetes mellitus) are associated with low HDL leve ls. Studies were therefore performed to examine the effect of albumin-bound -oleic acid on apo AI and apo AII production. The results showed that the a lbumin-oleate complex further increased the inhibitory effects of albumin o n apo AI and apo AII production. These data suggest how HDL metabolism may be affected at the hepatocellular level by alterations in plasma albumin co ncentrations and/or fatty acid mobilization in clinical situations characte rized by altered HDL levels. (C) 2000 Elsevier Science Ireland Ltd. All rig hts reserved.