Beige fat dissipates energy and functions as a defense against cold and obesity, but the mechanism for its development is unclear. We found that interleukin (IL)-25 signaling through its cognate receptor, IL-17 receptor B (IL-17RB), increased in adipose tissue after cold exposure and β3-adrenoceptor agonist stimulation. IL-25 induced beige fat formation in white adipose tissue (WAT) by releasing IL-4 and IL-13 and promoting alternative activation of macrophages that regulate innervation and up-regulate tyrosine hydroxylase (TH) up-regulation to produce more catecholamine including norepinephrine (NE). Blockade of IL-4Rα or depletion of macrophages with clodronate-loaded liposomes in vivo significantly impaired the beige fat formation in WAT. Mice fed with a high-fat diet (HFD) were protected from obesity and related metabolic disorders when given IL-25 through a process that involved the uncoupling protein 1 (UCP1)-mediated thermogenesis. In conclusion, the activation of IL-25 signaling in WAT may have therapeutic potential for controlling obesity and its associated metabolic disorders.

中文翻译：

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IL-25 诱导的巨噬细胞极化变化促进米色脂肪的发育并改善小鼠的代谢稳态。

米色脂肪消耗能量并起到抵御寒冷和肥胖的作用，但其发展机制尚不清楚。我们发现白细胞介素 (IL)-25 信号通过其同源受体 IL-17 受体 B (IL-17RB) 在冷暴露和 β3-肾上腺素受体激动剂刺激后在脂肪组织中增加。IL-25 通过释放 IL-4 和 IL-13 并促进巨噬细胞的替代激活来诱导白色脂肪组织 (WAT) 中的米色脂肪形成，这些巨噬细胞调节神经支配并上调酪氨酸羟化酶 (TH) 上调以产生更多的儿茶酚胺，包括去甲肾上腺素（东北）。在体内阻断 IL-4Rα 或用负载氯膦酸盐的脂质体消耗巨噬细胞会显着损害 WAT 中的米色脂肪形成。当通过涉及解偶联蛋白 1 (UCP1) 介导的产热过程给予 IL-25 时，高脂肪饮食 (HFD) 喂养的小鼠免受肥胖和相关代谢紊乱的影响。总之，WAT 中 IL-25 信号传导的激活可能具有控制肥胖及其相关代谢紊乱的治疗潜力。