Abstract 471: Triglyceride-rich Lipoprotein Lipolysis Products Induce Adipose Differentiation Related Protein Expression and Proatherogenic Cytokine Secretion in Monocytes
Elevated blood triglyceride levels are associated with an increased risk of atherosclerotic cardiovascular disease. Blood triglycerides are contained within very low density lipoproteins (VLDL) and chylomicrons, which are referred to as triglyceride-rich lipoproteins (TGRL). The enzyme lipoprotein lipase is responsible for the hydrolysis of these triglycerides, primarily into free fatty acids and glycerol. Our lab has shown that these lipolysis products induce lipid droplet formation in monocytes and can induce a proinflammatory state in multiple cell types. Other investigators have linked adipose differentiation related protein (ADRP, also known as perilipin 2 or adipophilin) to lipid droplet formation in monocyte-derived macrophage foam cells. The objectives of this study are to further understand the effects of TGRL lipolysis products on the formation of lipid droplets in monocytes and monocyte activation. We hypothesize that TGRL lipolysis products increase the expression of ADRP and the secretion of proatherogenic cytokines in THP-1 monocytes. In this study, we analyzed the global gene expression in THP-1 monocytes exposed to TGRL lipolysis products. ADRP was identified as a principal response lipid droplet associated gene induced by exposure to TGRL lipolysis products when compared to the control treatment. Induction of protein expression was analyzed by western blot. The TGRL lipolysis product treatment was also found to induce genes associated with atherosclerosis and monocyte adherence to endothelium including growth differentiation factor 15 (GDF15) and interleukin 8 (IL-8) when compared to the control treatment. We measured the secretion of GDF15 and IL-8 by ELISA. Our results indicate that mRNA and protein expression of ADRP and secretion of proatherogenic cytokines (GDF15 and IL-8) were increased in monocytes after exposure to TGRL lipolysis products. In conclusion, our study demonstrates that TGRL lipolysis products induce the expression of ADRP and the secretion of proatherogenic cytokines in monocytes. These results may indicate a role for TGRL lipolysis products in the increased risk of atherosclerotic cardiovascular disease for individuals with elevated blood triglyceride levels.
- © 2013 by American Heart Association, Inc.