炎症
兴奋剂
受体
胰高血糖素样肽1受体
Toll样受体
肿瘤坏死因子α
免疫系统
全身炎症
免疫学
内科学
医学
生物
先天免疫系统
作者
Ching Wong,Brent A. McLean,Laurie L. Baggio,Jacqueline A. Koehler,Rola Hammoud,Nikolaj Rittig,Julian M. Yabut,Randy J. Seeley,Theodore J. Brown,Daniel J. Drucker
出处
期刊:Cell Metabolism
[Elsevier]
日期:2024-01-01
卷期号:36 (1): 130-143.e5
被引量:11
标识
DOI:10.1016/j.cmet.2023.11.009
摘要
Summary
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) exert anti-inflammatory effects relevant to the chronic complications of type 2 diabetes. Although GLP-1RAs attenuate T cell-mediated gut and systemic inflammation directly through the gut intraepithelial lymphocyte GLP-1R, how GLP-1RAs inhibit systemic inflammation in the absence of widespread immune expression of the GLP-1R remains uncertain. Here, we show that GLP-1R activation attenuates the induction of plasma tumor necrosis factor alpha (TNF-α) by multiple Toll-like receptor agonists. These actions are not mediated by hematopoietic or endothelial GLP-1Rs but require central neuronal GLP-1Rs. In a cecal slurry model of polymicrobial sepsis, GLP-1RAs similarly require neuronal GLP-1Rs to attenuate detrimental responses associated with sepsis, including sickness, hypothermia, systemic inflammation, and lung injury. Mechanistically, GLP-1R activation leads to reduced TNF-α via α1-adrenergic, δ-opioid, and κ-opioid receptor signaling. These data extend emerging concepts of brain-immune networks and posit a new gut-brain GLP-1R axis for suppression of peripheral inflammation.
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