Obesity and neuroinflammatory phenotype in mice lacking endothelial megalin.

Abstract

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.

• Authors: Fernando Bartolome, Desiree Antequera, Eva Tavares, Consuelo Pascual, Rosario Maldonado, Antoni Camins, Eva Carro
• Journal: Journal of neuroinflammation (J Neuroinflammation) Vol. 14 Issue 1 Pg. 26 (01 31 2017) ISSN: 1742-2094 [Electronic] England
• PMID: 28143489 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Doublecortin Domain Proteins
• Glial Fibrillary Acidic Protein
• Low Density Lipoprotein Receptor-Related Protein-2
• Lrp2 protein, mouse
• Microtubule-Associated Proteins
• Neuropeptides
• STAT3 Transcription Factor
• Phosphopyruvate Hydratase

Topics

• Age Factors
• Animals
• Blood-Brain Barrier (metabolism, pathology)
• Brain (physiopathology)
• Cytokines (genetics, metabolism)
• Disease Models, Animal
• Doublecortin Domain Proteins
• Eating (genetics)
• Encephalitis (genetics, pathology)
• Endothelial Cells (metabolism)
• Glial Fibrillary Acidic Protein (metabolism)
• Low Density Lipoprotein Receptor-Related Protein-2 (deficiency, genetics)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Microtubule-Associated Proteins (metabolism)
• Mitochondria (pathology, ultrastructure)
• Neuropeptides (metabolism)
• Obesity (genetics, pathology)
• Phosphopyruvate Hydratase (metabolism)
• STAT3 Transcription Factor (metabolism)