生物
胰岛素抵抗
内分泌学
胰岛素
胰岛素受体
内科学
胶质纤维酸性蛋白
神经胶质
星形胶质细胞
下调和上调
细胞生物学
中枢神经系统
免疫学
医学
遗传学
免疫组织化学
基因
作者
Mroj Alassaf,Akhila Rajan
出处
期刊:PLOS Biology
[Public Library of Science]
日期:2023-11-07
卷期号:21 (11): e3002359-e3002359
被引量:7
标识
DOI:10.1371/journal.pbio.3002359
摘要
Obesity significantly increases the risk of developing neurodegenerative disorders, yet the precise mechanisms underlying this connection remain unclear. Defects in glial phagocytic function are a key feature of neurodegenerative disorders, as delayed clearance of neuronal debris can result in inflammation, neuronal death, and poor nervous system recovery. Mounting evidence indicates that glial function can affect feeding behavior, weight, and systemic metabolism, suggesting that diet may play a role in regulating glial function. While it is appreciated that glial cells are insulin sensitive, whether obesogenic diets can induce glial insulin resistance and thereby impair glial phagocytic function remains unknown. Here, using a Drosophila model, we show that a chronic obesogenic diet induces glial insulin resistance and impairs the clearance of neuronal debris. Specifically, obesogenic diet exposure down-regulates the basal and injury-induced expression of the glia-associated phagocytic receptor, Draper. Constitutive activation of systemic insulin release from Drosophila insulin-producing cells (IPCs) mimics the effect of diet-induced obesity on glial Draper expression. In contrast, genetically attenuating systemic insulin release from the IPCs rescues diet-induced glial insulin resistance and Draper expression. Significantly, we show that genetically stimulating phosphoinositide 3-kinase (Pi3k), a downstream effector of insulin receptor (IR) signaling, rescues high-sugar diet (HSD)-induced glial defects. Hence, we establish that obesogenic diets impair glial phagocytic function and delays the clearance of neuronal debris.
科研通智能强力驱动
Strongly Powered by AbleSci AI