Role of Cell Surface Receptors in Palmitic Acid-Induced Expression of IL-1β in Microglial Cells

Background/Objectives: Palmitic acid (PA), the most abundant saturated fatty acid in circulation, is elevated in obese individuals and has been implicated in promoting inflammation. However, its effects on inflammatory cytokine production in microglial cells and the involvement of cell surface receptors remain poorly characterized. Methods: In this study, we treated BV2 murine microglial cells with 200 µM PA or bovine serum albumin (BSA) control for 24 h and assessed IL-1β expression using semi-quantitative RT-PCR and/or ELISA. The roles of toll-like receptor (TLR)-2, TLR-4, G-protein-coupled receptor (GPR) 40, and GPR120 were investigated using siRNA knockdown and/or pharmacological inhibition. Results: Our studies found that PA treatment significantly increased IL-1β production as well as the mRNA expression of TLR-2, TLR-4, GPR40, and GPR120 compared to BSA controls. IL-1β expression correlated positively with TLR-2, TLR-4, and GPR40 levels. RNAi silencing of TLR-2, TLR-4, or GPR40 substantially diminished IL-1β expression in cells exposed to both BSA and PA. In contrast, neither RNAi silencing nor pharmacological inhibition of GPR120 suppressed IL-1β expression, suggesting that GPR120 may not mediate PA-induced inflammation. Conclusions: Our studies suggest that PA-induced production of IL-1β may be mediated via TLR-2, TLR-4, and GPR40, and that these cell surface receptors may serve as important molecular links between saturated fatty acids (SFAs) and neuroinflammation.