Fatty Acid-Binding Protein 4 is Essential for the Inflammatory and Metabolic Response of Microglia to Lipopolysaccharide

• DOI: 10.1007/s11481-023-10079-6
• Publication Date: 2023-08-09T10:02:02Z
• Authors: Yoshiteru Kagawa; Yi Ling Low; Jae Pyun; Umberto Doglione; Jennifer L. Short; Yijun Pan; Joseph A. Nicolazzo
• Keywords: Proinflammatory cytokine

Abstract Prolonged activation of microglia leads to excessive release proinflammatory mediators, which are detrimental brain health. Therefore, there significant efforts identify pathways mediating microglial activation. Recent studies have demonstrated that fatty acid-binding protein 4 (FABP4), a lipid binding protein, is critical player in macrophage–mediated inflammation. Given we previously identified FABP4 microglia, the aim this study was assess whether activity contributed inflammation, metabolism and immune function (i.e. immunometabolism) immortalised mouse (BV-2 cells) using stimulus lipopolysaccharide (LPS) induce general Microglial expression significantly increased following exposure LPS, an outcome associated with increase proliferation rate. LPS-stimulated BV-2 production reactive oxygen species (ROS) tumour necrosis factor-alpha (TNF-α), phosphorylation c-Jun N-terminal kinase (JNK), Toll-like receptor (TLR4), reduced uncoupling 2 (UCP2), all were reversed genetic silencing chemical inhibition BMS309403. The oxidation rate 3 H-oleic acid uptake H-2-deoxy-D-glucose modulated LPS activation, processes restored FABP4. This first report on role deleterious effects immunometabolism, suggesting may present as novel therapeutic target alleviate microglia-mediated neuroinflammation, commonly reported factor multiple neurodegenerative diseases. Graphical