ICH3, a selective alpha7 nicotinic acetylcholine receptor agonist, modulates adipocyte inflammation associated with obesity

摘要: The alpha7 nicotinic acetylcholine receptor (α7nAChR), involved in the modulation of inflammation and insulin sensitivity, is downregulated white adipose tissue (WAT) obese patients. This study aims to test ability a selective synthetic α7nAChR agonist, spirocyclic Δ2-isoxazoline derivative (R)-(−)-ICH3 (ICH3), counteract acute obesity-associated modifications WAT. We employed LPS-septic shock murine model, human primary adipocytes diet-induced (DIO) mice. Inflammatory factor expression was assessed by ELISA quantitative real-time PCR. Flow cytometry define WAT inflammatory infiltrate. Insulin signaling monitored quantification AKT phosphorylation. In septic ICH3 revealed antipyretic action reduced surge circulating cytokines. vitro, stimulation (10 µM) preserved viability adipocytes, decreased IL-6 mRNA (P < 0.05) blunted LPS-induced peak TNFα (P < 0.01). Chronic administration DIO mice associated with lower numbers CD8+ T cells changed factors (Hp, P < 0.05; CD301/MGL1, P < 0.01; Arg-1, P < 0.05). As compared untreated, exhibited improved skeletal muscle (P < 0.01) mirrored an response glucose load (ipGTT: P < 0.05 at 120 min). proved that anti-inflammatory drug, able reduce cytokines blunt effects obesity on profile, tolerance sensitivity.