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。
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
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.