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星形胶质细胞中的GLP-1受体信号调节脂肪酸氧化、线粒体完整性和功能
2020-05-20 23:39

近日,德国科隆大学Jens C. Brüning团队发现,星形胶质细胞中的GLP-1受体信号调节脂肪酸氧化、线粒体完整性和功能。这一研究成果于2020年5月19日在线发表在《细胞—代谢》上。

研究人员表明,胰高血糖素样肽(GLP)-1在培养的星形胶质细胞中抑制葡萄糖摄取并促进β-氧化。相反,表达神经胶质纤维酸性蛋白(GFAP)的星形胶质细胞中的GLP-1受体(GLP-1R)缺失会损害星形胶质细胞的线粒体完整性,并激活应激反应、增强成纤维细胞生长因子(FGF)21的产生,以及增加脑葡萄糖的摄取。
 
因此,在星形胶质细胞中缺乏GLP-1R表达的小鼠中,FGF21的中和或星形胶质细胞特异性FGF21敲除消除了葡萄糖耐受和学习的改善。
 
总的来说,这些实验揭示了星形胶质细胞GLP-1R信号传导在维持线粒体完整性中的作用,而缺乏GLP-1R信号传导则导致了适应性应激反应,进而改善了系统性葡萄糖稳态和记忆形成。
 
据了解,星形胶质细胞是大脑葡萄糖代谢和神经元功能的中央调节器。最近研究表明,它们通过响应能量状态感应激素瘦素和胰岛素来适应营养状态的变化,从而适应其功能。
 
附:英文原文

Title: GLP-1 Receptor Signaling in Astrocytes Regulates Fatty Acid Oxidation, Mitochondrial Integrity, and Function

Author: Katharina Timper, Almudena del Río-Martín, Anna Lena Cremer, Stephan Bremser, Jens Alber, Patrick Giavalisco, Luis Varela, Christian Heilinger, Hendrik Nolte, Aleksandra Trifunovic, Tamas L. Horvath, Peter Kloppenburg, Heiko Backes, Jens C. Brüning

Issue&Volume: 2020-05-19

Abstract: Astrocytes represent central regulators of brain glucose metabolism and neuronal function. They have recently been shown to adapt their function in response to alterations in nutritional state through responding to the energy state-sensing hormones leptin and insulin. Here, we demonstrate that glucagon-like peptide (GLP)-1 inhibits glucose uptake and promotes β-oxidation in cultured astrocytes. Conversely, postnatal GLP-1 receptor (GLP-1R) deletion in glial fibrillary acidic protein (GFAP)-expressing astrocytes impairs astrocyte mitochondrial integrity and activates an integrated stress response with enhanced fibroblast growth factor (FGF)21 production and increased brain glucose uptake. Accordingly, central neutralization of FGF21 or astrocyte-specific FGF21 inactivation abrogates the improvements in glucose tolerance and learning in mice lacking GLP-1R expression in astrocytes. Collectively, these experiments reveal a role for astrocyte GLP-1R signaling in maintaining mitochondrial integrity, and lack of GLP-1R signaling mounts an adaptive stress response resulting in an improvement of systemic glucose homeostasis and memory formation.

DOI: 10.1016/j.cmet.2020.05.001

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30240-0

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:31.373
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx


本期文章:《细胞—代谢》:Online/在线发表

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