G-Protein-Coupled Receptor 41 (GPR41) as a Therapeutic Target for Metabolic Endotoxemia: Mechanistic Insights into AR420626-Induced Autophagy and Nuclear Factor kappa B (NF-κB) Suppression
In vitro study reveals GPR41 activation suppresses endotoxin-induced inflammation via autophagy in macrophages, highlighting a novel therapeutic strategy for metabolic endotoxemia.
Key Points
To determine the molecular mechanisms by which the GPR41 agonist AR420626 protects macrophages against lipopolysaccharide-induced inflammatory stress and metabolic endotoxemia.
Exposed murine RAW 264.7 macrophages to lipopolysaccharide (LPS) to model endotoxin stress in vitro.
Administered the selective GPR41 agonist AR420626 alone and in combination with pharmacological autophagy inhibitors or GPR41-targeted knockdown.
AR420626 treatment significantly inhibited LPS-induced production of nitric oxide, IL-6, MCP-1, and iNOS by downregulating NF-κB pathway activation.
GPR41 activation stimulated autophagic flux, marked by enhanced LC3-I to LC3-II conversion; blocking autophagy or knocking down GPR41 eliminated AR420626-dependent NF-κB suppression and anti-inflammatory protection.