Elaidic Acid Develops Arteriosclerosis via TLR4 Signaling System

Background/Aims: Intake of trans fatty acids formed in the process of industrial hydrogenation of fats has been reported to increase the risk of arteriosclerosis and cardiovascular disease, which is the leading cause of death worldwide. However, there are many unclear points about the detailed mechanism of action of trans fatty acids in the disease onset process. Methods: We analyzed the effects of elaidic acid, which is a major component of industrial trans fatty acids, on adipocytokine expression and macrophage differentiation. Results: The expression of TNF-α was found to be elevated in human breast cancer-derived YMB cells and PMAstimulated human monocyte-derived U937 cells by real-time PCR. TNF-α protein inhibited the expression of an anti-arteriosclerotic adipocytokine adiponectin in YMB cells. Several inhibitors of TNF-α signalling system and knockdown of TNF-α expression by siRNA recovered the expression of adiponectin. In PMA-stimulated U937 cells, elaidic acid increased the expression of the TLR4 coreceptor CD14, ICAM-1 and both differentiation markers CD68 and CD147, and also promoted phagocytosis. These results and TNF-α expression were significantly inhibited by a TLR4 inhibitor TAK-242. In addition, inhibition of adiponectin expression by elaidic acid was not observed in primary cultured fat cells from TLR4-deficient mice. These facts suggest that elaidic acid inhibits the expression of adiponectin and in parallel promotes the differentiation of monocyte macrophages, phagocytosis and macrophage foaming through the TLR4 signalling system which causes arteriosclerosis. Conclusion: There is close relationship between elaidic acid and arteriosclerosis.