Obesity and neuroinflammatory phenotype in mice lacking endothelial megalin.
Obesity and neuroinflammatory phenotype in mice lacking endothelial megalin.
复制标题
缺乏内皮梅加林的小鼠的肥胖和神经炎症表型。
DOI：
10.1186/s12974-017-0800-2
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发表时间：
2017-01-31
影响因子：
9.3
通讯作者：
Carro E
中科院分区：
文献类型：
--
作者：
Bartolome F;Antequera D;Tavares E;Pascual C;Maldonado R;Camins A;Carro E
多配体受体megalin控制大脑对许多配体的摄取，包括胰岛素和瘦素。尽管megalin在这些代谢相关激素的运输中发挥作用，但megalin在血脑屏障（BBB）中的作用尚未在代谢调节的背景下进行探索。在这里，我们调查的作用，脑内皮细胞巨蛋白在能量代谢和瘦素信号转导使用内皮细胞特异性巨蛋白缺陷（EMD）小鼠模型。我们发现megalin在正常饮食的小鼠中对保护小鼠免于发展肥胖和代谢综合征很重要。EMD小鼠通过触发几种促炎细胞因子而发生神经炎症，表现出神经发生减少和线粒体失调。这些结果暗示脑内皮巨蛋白表达通过瘦素信号通路在肥胖相关的代谢变化中，提出肥胖和神经变性之间的潜在联系。本文的在线版本（doi：10.1186/s12974-017-0800-2）包含补充材料，可供授权用户使用。
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. The online version of this article (doi:10.1186/s12974-017-0800-2) contains supplementary material, which is available to authorized users.