Ozempic Strikes a Nerve: Deciphering a Role in Brainstem-Mediated Inflammation Control
Description: The blockbuster drug semaglutide and similar anti-obesity GLP-1 receptor agonists (GLP-1RAs) exert anti-inflammatory effects independent of weight loss, and are being explored for a range of inflammatory diseases. How GLP-1RAs mitigate inflammation is unknown.Yet, the immune-suppressive action of GLP-1RAs require brain GLP-1Rs, and semaglutide activates dorsal vagal complex (DVC) neurons that are anti-inflammatory. I hypothesize that this entails specific DVC neurons and a neural pathway involving α7 nicotinic acetylcholine receptors (α7nAChRs). According to the prevailing concept, this would include the cholinergic vagal reflex that originates from the DVC and relies on immune system α7nAChRs. However, I reveal that α7nAChRs are not expressed by immune cells, but by abdominal noradrenergic ganglionic neurons innervating many organs, suggesting a revised model.The purpose is to reveal anti-inflammatory mechanisms of semaglutide, DVC neurons, and neural reflexes, and their potential crosstalk. Using genetic tools, circuit manipulations, and inflammatory models in mice, my aims are to determine:1. If sympathetic ganglionic α7nAChRs suppress immune responses (year 1-3).2. If semaglutide’s anti-inflammatory effects depend on certain DVC neurons and a downstream circuit involving ganglionic α7nAChRs (year 2-5).My research may reshape our understanding of neuroimmune inflammation control and reveal semaglutide’s anti-inflammatory mode of action.
Funder: Vetenskapsrådet
Amount: SEK 3,000,000
Funding type: research
Funder scheme: Project grant
Start date: 2026-01-01
End date: 2028-12-31
Investigator: Johan Ruud
Institution: University of Gothenburg
Funded outputs count: 1
Funder award ID: 2025-03430
OpenAlex ID: G2285595879