FABP7 is increased in Progressive Multiple Sclerosis and induces a Pro-Inflammatory Phenotype in Monocytes through a Glycolytic Switch
Multiple sclerosis (MS) involves dysregulation of innate immune cells including monocytes, especially in progressive MS. Fatty acid binding proteins (FABP) are essential for fatty acid transport and metabolism in multiple cell types. FABP7 (Brain-FABP) maintains metabolic function in astrocytes and neural stem cells, but its effect on monocytes is unknown. Here we find elevated levels of FABP7 in the serum and cerebrospinal fluid of patients with secondary progressive MS. Elevated serum FABP7 levels positively correlate with higher disability scores, brain lesion volumes, and lower brain volumes. FABP7 levels are increased in astrocytes from MS postmortem brain lesion. Mechanistically, in vitro treatment of FABP7 induces CD16, CD80, and IL-1beta expression in monocytes via increased glycolysis. FABP7-induced gene expression reflects enhanced inflammation, chemotaxis and glucose metabolism. In conclusion, we find that FABP7 induces proinflammatory profiles in monocytes, correlates with disability and represents a potential biomarker and therapeutic target for progressive MS.