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Based on functional categories of the DEGs, we further proposed a model to explain the etiology and pathogenesis of FLHS. IL6 and SOCS3 mediate inflammatory responses and the satiety hormone of leptin, induce dysfunction of Jak-STAT signaling pathway, leading to insulin resistance and lipid metabolic disorders. Conversely, CNTF may reduce tissue destruction during inflammatory attacks and confer protection from inflammation-induced insulin resistance in FLHS chickens. Conclusion These findings highlight the therapeutic implications of ta