Obesity and neuroinflammatory phenotype in mice lacking endothelial megalin

Background: the multiligand receptor megalin controls the brain uptake of a number of ligands,including insulin and leptin. despite the role of megalin in the transport of these metabolically relevant hormones,the role of megalin at the blood-brain-barrier (bbb) has not yet been explored in the context of metabolic regulation. methods: here we investigate the role of brain endothelial megalin in energy metabolism and leptin signaling using an endothelial cell-specific megalin deficient (emd) mouse model. results: we found megalin is important to protect mice from developing obesity and metabolic syndrome when mice are fed a normal chow diet. emd mice developed neuroinflammation,by triggering several pro-inflammatory cytokines,displayed reduced neurogenesis and mitochondrial deregulation. conclusions: these results implicate brain endothelial megalin expression in obesity-related metabolic changes through the leptin signaling pathway proposing a potential link between obesity and neurodegeneration. © 2017 the author(s).