Short-Chain Fatty Acids Suppress MCP-1 and Cellular Aging Induced by Lipopolysaccharides under High-Concentration Glucose

Abstract

Background: High glucose levels, as observed in diabetic patients, enhances the inflammatory response of Porphyromonas gingivalis-Lipopolysaccharide (Pg-LPS) in various cell types and may thus worsen atherosclerosis and other inflammatory diseases. Short-Chain Fatty Acids (SCFAs) have been suggested to defend against inflammation and atherosclerosis, but, it is unknown whether SCFAs also affect aging, which accelerates atherosclerosis. We investigated the inhibitory effects of SCFAs on an aging marker, i.e., telomere length, and an atherogenic factor, Monocyte Chemoattractant Protein-1 (MCP-1), in Human Umbilical Vein Endothelial Cells (HUVECs) exposed to Pg-LPS under high glucose. Methods: We treated HUVECs with the three SCFAs acetic acid, propionic acid and butyric acid and then stimulated the cells with 0.1 µg/mL Pg-LPS + high (20 mM) glucose. We then measured the MCP-1 mRNA expression and telomere length by real-time RT-PCR. Results: Acetic acid or propionic acid at ≥0.5 mM and butyric acid at ≥0.25 mM suppressed the enhanced expression of MCP-1 mRNA induced by Pg-LPS + high glucose to the level in unstimulated HUVECs. The NF-κB activation, which promotes the transcription of MCP-1 mRNA, and MCP-1 protein production enhanced by Pg-LPS + high glucose were suppressed by acetic acid. The telomere length of HUVECs exposed to Pg-LPS + high glucose was significantly decreased by 30% compared to that in unstimulated HUVECs. Acetic acid or propionic acid at 1 mM and butyric acid 0.5 mM restored the telomere length to levels comparable to those in unstimulated HUVECs. Conclusion: SCFAs may reduce the atherogenic risk and aging risk of periodontal disease in individuals with diabetes mellitus.