RT Journal Article
T1 Obesity and neuroinflammatory phenotype in mice lacking endothelial megalin.
A1 Bartolome, Fernando
A1 Antequera, Desiree
A1 Tavares, Eva
A1 Pascual, Consuelo
A1 Maldonado, Rosario
A1 Camins, Antoni
A1 Carro, Eva
K1 Blood–brain barrier
K1 Hyperleptinemia
K1 Inflammation
K1 Leptin resistance
K1 Megalin
K1 Obesity
AB 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. 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. 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. 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.
YR 2017
FD 2017-01-31
LK http://hdl.handle.net/10668/10825
UL http://hdl.handle.net/10668/10825
LA en
DS RISalud
RD Apr 18, 2025