Central glucagon-like peptide 1 receptor activation inhibits Toll-like receptor agonist-induced inflammation 2024 Wong et al

Highlights

• GLP-1R agonism attenuates TLR-induced inflammation
• Semaglutide reduces the severity of polymicrobial inflammation
• Anti-inflammatory actions of GLP-1R agonists require CNS GLP-1Rs
• GLP-1R agonists reduce inflammation through CNS adrenergic and opioid GPCRs

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.

Paywall, https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00420-5

 

Obesity drugs have another superpower: taming inflammation

The latest generation of anti-obesity drugs has taken the world by storm, thanks to their effectiveness at treating diabetes and reducing weight. But these drugs also have a less well-known superpower: the ability to suppress inflammation.

Evidence suggest that the drugs classified as GLP-1 receptor agonists — a category that includes brand names such as Mounjaro and Wegovy — can reduce inflammation in the liver, kidneys and heart. The drugs even seem to dial down inflammation in the brain, leading scientists to hope that the compounds could be used to treat Parkinson’s and Alzheimer’s diseases, both of which are characterized by brain inflammation. A recent review1 listed more than 20 clinical trials that are exploring the drugs as therapies for the two conditions.

“The next generation of drugs could be even more targeted to reduce these new inflammation pathways that we’ve identified,” says Daniel Drucker, an endocrinologist at the University of Toronto in Canada who co-authored a study2 investigating how the drugs dampen inflammation that was published last month. “Maybe they would be more effective.”

https://www.nature.com/articles/d41586-024-00118-4

 

Some ME or “CFS” patients already trying these drugs for weight loss. Some seem to find “reduces fatigue”, some don’t, some don’t tolerate.
https://www.reddit.com/r/cfs/search...e4ab&iId=2069e258-3766-474d-96d7-81fb39119742