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Diet-induced glial insulin resistance impairs the clearance of neuronal debris
The risk of neurodegenerative illnesses is greatly increased by obesity. However, the exact processes behind this association are yet unknown. Inflammation, poor nervous system recovery, and neuronal death can arise from delayed clearance of neuronal debris, which makes defects in glial phagocytic function a crucial aspect of neurodegenerative diseases. Growing data suggests that weight, eating habits, and systemic metabolism are all impacted by glial activity and that glial function may be regulated by diet. Although it is known that glial cells respond to insulin, it is not known if eating a diet high in fat might cause glial insulin resistance, which would, therefore, affect glial phagocytic activity. In this study, Alassaf and Rajan (2023) demonstrate that a persistent obesogenic diet causes glial insulin resistance and compromises the removal of neural debris using a Drosophila model. In particular, exposure to an obesogenic diet reduces the baseline and injury-induced expression of the glia-linked Draper phagocytic receptor. Constitutive stimulation of Drosophila insulin-producing cells’ (IPCs) systemic insulin secretion imitates the impact of an obesity-induced diet on the expression of glial Draper. On the other hand, diet-induced glial insulin resistance and Draper expression are reversed when systemic insulin release from the IPCs is genetically impaired. Notably, the authors highlight that glial abnormalities generated by a high-sugar diet (HSD) may be prevented by genetically activating phosphoinositide 3-kinase (Pi3k), a downstream agent of insulin receptor (IR) signaling. The authors demonstrate that obesogenic diets cause a delay in the removal of neural debris by hindering glial phagocytic activity. [NPID: Insulin resistance, insulin signaling, obesity, diet, insulin, Drosophila melanogaster, glycolysis]
Year: 2023
