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We explored the effect of citronellal treatment on olfactory receptor 4M1 subtype (OR4M1) signaling in insulin resistance and Type II diabetes in rats. We aimed to validate the anti\u2010diabetic effect of citronellal through Asprosin\/OR4M1 modulation. Exploring new antidiabetics and pharmacological targets is important to improve quality of life and limit complications. The model was established in Sprague\u2010Dawley rats by a high\u2010fat diet for 4\u00a0weeks followed by a single low\u2010dose streptozotocin (STZ) (35 mg\/kg\/ip). One week after STZ injection, oral citronellal (100\u00a0mg\/kg) was administered for 4\u00a0weeks. Citronellal lowered serum glucose and triglycerides and ameliorated OGTT and HOMA\u2010IR results. Docking results revealed that citronellal blocked the Asprosin binding site at OR4M1. The hepatic expression of OR4M1 and Asprosin was reduced. Citronellal lowered cAMP levels causing attenuated levels of protein kinase A and downstream gluconeogenic enzymes: glucose\u20106\u2010phosphatase and phosphoenolpyruvate carboxykinase. Citronellal also inhibited the expression of hepatic TLR\u20104 and inhibited JNK phosphorylation. Citronellal attenuated hepatic levels of NF\u2010\u03baB, p\u2010NF\u2010\u03baB, and downstream proteins MCP\u20101 and TNF\u2010\u03b1. These results suggest that citronellal alleviates insulin resistance by mitigating Asprosin\/OR4M1 and Asprosin\/TLR4\/JNK signaling.<\/jats:p>","DOI":"10.1002\/mnfr.202400654","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T10:52:22Z","timestamp":1737024742000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Citronellal Alleviates Insulin Resistance in High\u2010Fat Diet\/Streptozocin Model: Role of Asprosin\/Olfactory Receptor Axis"],"prefix":"10.1002","volume":"69","author":[{"given":"Aya","family":"Abdelaziz","sequence":"first","affiliation":[{"name":"Biochemistry Department Faculty of Pharmacy Mansoura University  Mansoura Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousra M.","family":"El\u2010Far","sequence":"additional","affiliation":[{"name":"Biochemistry Department Faculty of Pharmacy Mansoura University  Mansoura 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