Our previous research identified interleukin‐4 (IL‐4) as a key regulator of glucose/lipid metabolism, circulatory leptin levels, and insulin action, suggesting its potential as a therapeutic target for obesity and related complications. This study aimed to further elucidate the role of IL‐4 in regulating hypothalamic appetite‐controlling neuropeptides using leptin dysfunctional Leptin145E/145E mice as the experimental model. IL‐4 significantly reduces body weight, food intake, and serum glucose levels. Our data demonstrated that IL‐4 exhibits multiple functions in regulating hypothalamic appetite control, including downregulating orexigenic agouti‐related peptide and neuropeptide Y levels, promoting expression of anorexigenic proopiomelanocortin, alleviating microenvironmental hypothalamic inflammation, enhancing leptin and insulin pathway, and attenuating insulin resistance. Furthermore, IL‐4 promotes uncoupling protein 1 expression of white adipose tissue (WAT), suggesting its role in triggering WAT‐beige switch. In summary, this study uncovers novel function of IL‐4 in mediating food‐intake behaviors and metabolic efficiency by regulating hypothalamic appetite‐control and WAT browning activities. These findings support the therapeutic potential of targeting hypothalamic inflammation and reducing adiposity through IL‐4 intervention for tackling the pandemic increasing prevalence of obesity and associated metabolic disorders.

中文翻译：

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Interleukin-4 通过调节瘦素突变小鼠的胰岛素-AKT 和 JAK-STAT 信号传导抑制下丘脑食欲控制

我们之前的研究发现白细胞介素-4 (IL-4) 是葡萄糖/脂质代谢、循环瘦素水平和胰岛素作用的关键调节剂，表明其作为肥胖和相关并发症的治疗靶点的潜力。本研究旨在利用瘦素功能失调的瘦素进一步阐明IL-4在调节下丘脑食欲控制神经肽中的作用145E/145E以小鼠为实验模型。 IL-4 显着降低体重、食物摄入量和血糖水平。我们的数据表明，IL-4在调节下丘脑食欲控制方面表现出多种功能，包括下调促食欲刺鼠相关肽和神经肽Y的水平，促进促食欲阿黑皮素原的表达，减轻微环境下丘脑炎症，增强瘦素和胰岛素途径，并减弱胰岛素抵抗。此外，IL-4 促进白色脂肪组织 (WAT) 解偶联蛋白 1 的表达，表明其在触发 WAT-米色转换中的作用。总之，本研究揭示了 IL-4 通过调节下丘脑食欲控制和 WAT 褐变活动来介导食物摄入行为和代谢效率的新功能。这些发现支持通过 IL-4 干预来针对下丘脑炎症和减少肥胖的治疗潜力，以应对肥胖和相关代谢紊乱患病率增加的流行病。