Central glucagon-like peptide 1 receptor activation inhibits Toll-like receptor agonist-induced inflammation.
Cell Metab
; 36(1): 130-143.e5, 2024 01 02.
Article
in En
| MEDLINE
| ID: mdl-38113888
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sepsis
/
Diabetes Mellitus, Type 2
Limits:
Humans
Language:
En
Journal:
Cell Metab
/
Cell metab
/
Cell metabolism
Journal subject:
METABOLISMO
Year:
2024
Document type:
Article
Affiliation country:
Canada
Country of publication:
United States