title: Obesity and neuroinflammatory phenotype in mice lacking endothelial megalin.
abstract: 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.
authors.affiliation: Neurodegenerative Disorders Group, Instituto de Investigacion Hospital 12 de Octubre (i + 12), Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Bartolome
authors.affiliation: Neurodegenerative Disorders Group, Instituto de Investigacion Hospital 12 de Octubre (i + 12), Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain.
authors.forename: Desiree
authors.initials: D
authors.lastname: Antequera
authors.affiliation: Clinical and Experimental Pharmacology Research Unit, Valme University Hospital, Seville, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Tavares
authors.affiliation: Neurodegenerative Disorders Group, Instituto de Investigacion Hospital 12 de Octubre (i + 12), Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Pascual
authors.affiliation: Clinical and Experimental Pharmacology Research Unit, Valme University Hospital, Seville, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: Maldonado
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain.|Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Institut de Biomedicina de la UB (IBUB), Universitat de Barcelona, Barcelona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Camins
authors.affiliation: Neurodegenerative Disorders Group, Instituto de Investigacion Hospital 12 de Octubre (i + 12), Madrid, Spain. carroeva@h12o.es.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain. carroeva@h12o.es.
authors.forename: Eva
authors.initials: E
authors.lastname: Carro
mesh_terms: D000367:Age Factors; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000503:physiopathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D004435:Eating / Q000235:genetics; D004660:Encephalitis / Q000235:genetics* / Q000473:pathology*; D042783:Endothelial Cells / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000172:deficiency* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000473:pathology / Q000648:ultrastructure; D009479:Neuropeptides / Q000378:metabolism; D009765:Obesity / Q000235:genetics* / Q000473:pathology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D016207:Cytokines; D000089622:Doublecortin Domain Proteins; D005904:Glial Fibrillary Acidic Protein; D026561:Low Density Lipoprotein Receptor-Related Protein-2; C055127:Lrp2 protein, mouse; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D050796:STAT3 Transcription Factor; D010751:Phosphopyruvate Hydratase
keywords: Blood–brain barrier; Hyperleptinemia; Inflammation; Leptin resistance; Megalin; Obesity