The function of gangliosides, sialic acid-containing glycolipids, on the secretion and assembly of apoB-containing lipoproteins is poorly understood. Here, we report that the GD3 synthase is involved in apoB secretion in retinoic acid (RA)-treated Chang liver cells via transcriptional induction of microsomal triglyceride transfer protein (MTP). The overexpression of GD3 synthase in Chang liver cells increases the expression of the MTP gene, but GM3 synthase-transfected cells did not. The levels of GM3 and GD3 gangliosides in each of the transfected cells were increased in the cell extract as well as the medium. In addition, GD3 synthase-transfected cells showed an increased secretion of triglyceride-enriched apoB. In contrast, the triglyceride content in GM3 synthase-transfected cells was relatively lower. Treatment with small interfering RNAs (siRNAs) and GD3 antibody decreased apoB secretion. These results indicate that plasma membrane associated GD3 play important roles in apoB secretion, and that an enhancement in GD3 levels might be a risk factor for the development of atherosclerosis by increasing the secretion of triglyceride-enriched apoB containing lipoproteins. (c) 2007 Elsevier Inc. All rights reserved.