Obesity and neuroinflammatory phenotype in mice lacking endothelial megalin

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 met...

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Bibliographic Details
Published in:Journal of neuroinflammation 2017-01, Vol.14 (1), p.26-26, Article 26
Main Authors: Bartolome, Fernando, Antequera, Desiree, Tavares, Eva, Pascual, Consuelo, Maldonado, Rosario, Camins, Antoni, Carro, Eva
Format: Article
Language:English
Subjects:
Age Factors
Animals
Bioenergetics
Blood-Brain Barrier - metabolism
Blood-Brain Barrier - pathology
Brain - physiopathology
Cellular signal transduction
Cytokines - genetics
Cytokines - metabolism
Disease Models, Animal
Eating - genetics
Encephalitis - genetics
Encephalitis - pathology
Endothelial Cells - metabolism
Endothelium
Energy metabolism
Genetic aspects
Glial Fibrillary Acidic Protein - metabolism
Leptin
Low Density Lipoprotein Receptor-Related Protein-2 - deficiency
Low Density Lipoprotein Receptor-Related Protein-2 - genetics
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Microtubule-Associated Proteins - metabolism
Mitochondria - pathology
Mitochondria - ultrastructure
Neuropeptides - metabolism
Obesity
Obesity - genetics
Obesity - pathology
Phosphopyruvate Hydratase - metabolism
Physiological aspects
STAT3 Transcription Factor - metabolism
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Summary: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.
ISSN:1742-2094
1742-2094
DOI:10.1186/s12974-017-0800-2