Palmitic Acid Regulation of Microglial Immune Function

Microglial are the primary immune cells of the central nervous system (CNS) and when activated release proinflammatory cytokines. Obesity is an epidemic that is characterized by elevated levels of saturated fatty acids (SFAs), most predominantly palmitic acid (PA). The effect of PA on microglial immune function remains poorly understood. The ultimate aim of this study is to elucidate the mechanisms by which PA affects microglial function. In this study we treated BV2 murine microglial cells with 200 μM PA or BSA control and measured mRNA expression levels with semi-quantitative RT-PCR and protein levels using ELISA. The roles of toll-like receptors (TLR), TLR2 and TLR4, as well as CD36, GPR40 and GPR120 in PA-induced inflammation was investigated using siRNA knockdown and/or pharmacological inhibitors namely, Grassofermata, Lipofermata, and 2-Bromopalmitate (BrPa). Finally, we utilized Lipopolysaccharide (LPS), an endotoxin, to investigate if there was a synergistic effect with PA. Our studies found that PA significantly increased microglial proinflammatory cytokine expression and created a more robust induction in response to LPS. PA also increased expression of CD36, TLR2, TLR4, GPR40, and GPR120; conversely knockdown of aforementioned genes decreased cytokine production for all genes except GPR120, indicating that it does not mediate PA-induced inflammation. Pharmacological inhibition also showed a decrease in inflammation indicating PA-induced inflammation extends to more than just cell surface interactions. Our findings indicate that increased levels of circulating PA may trigger brain inflammation. Our results indicate targeting CD36, GPR40, and TLRs expression may reduce inflammation. In addition, the use of pharmacological inhibitors could represent a potential therapeutic alternative to obesity induced inflammation.