Secretion of triacylglycerol-poor VLDL particles from McA-RH7777 cells expressing human hepatic lipase

Hepatic lipase (HL) plays a role in the catabolism of apolipoprotein (apo)B-containing lipoproteins through its lipolytic and ligand-binding properties. We describe a potential intracellular role of HL in the assembly and secretion of VLDL. Transient or stable expression of HL in McA-RH7777 cells resulted in decreased (by 40%) incorporation of [H-3]glycerol into cell-associated and secreted triacylglycerol (TAG) relative to control cells. However, incorporation of [S-35]methionine/cysteine into cell and medium apoB-100 was not decreased by HL expression. The decreased H-3-TAG synthesis/secretion in HL expressing cells was not attributable to decreased expression of genes involved in lipogenesis. Fractionation of medium revealed that the decreased [H-3]TAG from HL expressing cells was mainly attributable to decreased VLDL. Expression of catalytically-inactive HL (HLSG) (Ser-145 at the catalytic site was substituted with Gly) in the cells also resulted in decreased secretion of VLDL-[H-3]TAG. Examination of lumenal contents of microsomes showed a 40% decrease in [H-3]TAG associated with lumenal lipid droplets in HL or HLSG expressing cells as compared with control. The microsomal membrane-associated [H-3]TAG was decreased by 50% in HL expressing cells but not in HLSG expressing cells. Thus, expression of HL, irrespective of its lipolytic function, impairs formation of VLDL precursor [H-3]TAG in the form of lumenal lipid droplets.jlr These results suggest that HL expression in McA-RH7777 cells result in secretion of [H-3]TAG-poor VLDL.-Bamji-Mirza, M., M. Sundaram, S. Zhong, E. F. Yao, R. Parks, and Z. Yao. Secretion of triacylglycerol-poor VLDL particles from McA-RH7777 cells expressing human hepatic lipase. J. Lipid Res. 2011. 52: 540-548.