内分泌学
内科学
小胶质细胞
生物
前列腺素E2
受体
下丘脑
胰岛素抵抗
吞咽不足
炎症
胰岛素
医学
作者
Anzela Niraula,Rachael D Fasnacht,Kelly M Ness,Jeremy M Frey,Sophia A Cuschieri,Mauricio D Dorfman,Joshua P Thaler
出处
期刊:Diabetes
[American Diabetes Association]
日期:2022-11-01
摘要
In rodents, susceptibility to diet-induced obesity requires microglial activation, but the molecular components of this pathway remain incompletely defined. Prostaglandin E2 (PGE2) levels increase in the mediobasal hypothalamus during high fat diet (HFD) feeding, and the PGE2 receptor EP4 regulates microglial activation state and phagocytic activity, suggesting a potential role for microglial EP4 signaling in obesity pathogenesis. To test the role of microglial EP4 in energy balance regulation, we analyzed the metabolic phenotype in a cell-specific EP4 knockout mouse model. Microglial EP4 deletion markedly reduced weight gain and food intake in response to HFD feeding. In correspondence with this lean phenotype, insulin sensitivity was also improved in the HFD-fed MG-EP4 KO mice though glucose tolerance remained surprisingly unaffected. Mechanistically, EP4-deficient microglia showed an attenuated phagocytic state marked by reduced CD68 expression and fewer contacts with POMC neuron processes. These cellular changes observed in the microglial EP4 knockout mice corresponded with an increased density of POMC neurites extending into the paraventricular nucleus. These findings reveal that microglial EP4 signaling promotes body weight gain and insulin resistance during HFD feeding. Furthermore, the data suggest that curbing microglial phagocytic function may preserve POMC cytoarchitecture and PVN input to limit overconsumption during diet-induced obesity.
科研通智能强力驱动
Strongly Powered by AbleSci AI