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Cyst fluid (CF), rich in inflammatory mediators, is implicated in CP\u2010related obesity, though the precise mechanism remains unclear. This study investigated the impact of CF or C\u2010X\u2010C motif chemokine ligand\u20101 (CXCL1) injections on body weight, Lee index, plasma lipid profiles, hepatic lipid accumulation, leptin levels, NF\u2010\u03baB pathway, the suppressor of cytokine signaling 3 (SOCS3) expression, and leptin sensitivity in rats. Bioinformatics was employed to identify differentially expressed genes (DEGs) between CF\/CXCL1\u2010treated and control SY5Y cells, as well as to confirm enriched pathways. Western blotting was used for experimental validation, including the effects of sodium salicylate (SS) on leptin sensitivity in SY5Y cells. Injecting CF or CXCL1 into the brain, without hypothalamic damage, led to increased body weight, Lee index, and hepatic lipid accumulation in rats, alongside elevated fasting blood glucose, triglycerides, and total cholesterol, while high\u2010density lipoprotein cholesterol levels decreased. Additionally, CF and CXCL1 could induce elevated leptin levels, a higher leptin\u2010to\u2010body weight ratio, and resistance to exogenous leptin by activating the NF\u2010\u03baB pathway and upregulating the expression of SOCS3 in rats. Further validation confirmed that CF and CXCL1 suppress leptin signaling by activating the NF\u2010\u03baB pathway and upregulating SOCS3. Moreover, SS mitigated the inhibitory effects of CF or CXCL1 on leptin signaling, preserving leptin sensitivity in SY5Y cells. These results highlight the obesogenic role of CF and CXCL1, offering insights into the development of morbid obesity through inflammatory factor\u2010mediated leptin resistance, independent of hypothalamic damage. SS may serve as a promising therapeutic approach for CP\u2010associated obesity, though additional clinical studies are necessary to confirm its efficacy.<\/jats:p>","DOI":"10.1096\/fj.202402216rr","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T06:49:22Z","timestamp":1733813362000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Inflammatory mediator contributes to leptin resistance and obesity in craniopharyngioma"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4971-8171","authenticated-orcid":false,"given":"Youchao","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Ningbo University  Zhejiang China"},{"name":"Department of Neurosurgery, Beijing Tiantan Hospital Capital Medical University  Beijing 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