Purpose. Targeting white adipose tissue (WAT) beiging has been proposed as an effective way to increase thermogenesis and improve glucose metabolism. Neuromedin U (NMU) is a neuropeptide that could increase energy expenditure, while its effects on WAT beiging and glucose homeostasis remain to be investigated. Methods. Male C57BL/6 mice were fed with high fat diet (HFD) to induce obesity and hyperglycemia and then treated with chronic subcutaneous injection of NMU. Body weight and food intake were recorded daily. After 14 days of injection, intraperitoneal glucose tolerance tests and 18F-fluorodeoxyglucose micro-positron emission tomography/computed tomography (18F-FDG micro-PET/CT) scans were conducted. Subcutaneous WAT (sWAT) and interscapular brown adipose tissue were collected for the evaluation of adipocyte size, expression of uncoupling protein 1 (Ucp1), and other thermogenic-related genes. Stromal vascular fraction of subcutaneous WAT was extracted for the measurement of type 2 innate lymphocytes (ILC2s) proportions. Results. Glucose tolerance was markedly improved by peripherally administered NMU. Micro-PET/CT suggested that NMU promoted WAT beiging, which was further confirmed by haematoxylin and eosin (H&E) staining and immunohistochemistry. In diet-induced-obese (DIO) mice, NMU activated thermogenic-related genes in WAT. In addition, NMU stimulated ILC2s in the stromal vascular fraction of WAT. Conclusion. Taken together, our study indicates that peripheral administration of NMU is a potential therapeutic strategy for the promotion of WAT beiging and the improvement of impaired glucose tolerance.

中文翻译：

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NMU的外周给药促进白色脂肪组织变黄并提高葡萄糖耐受性

目的。已提出针对白色脂肪组织 (WAT) 米色作为增加产热和改善葡萄糖代谢的有效方法。Neuromedin U (NMU) 是一种可以增加能量消耗的神经肽，而其对 WAT 米色和葡萄糖稳态的影响仍有待研究。方法. 给雄性 C57BL/6 小鼠喂食高脂饮食 (HFD) 以诱导肥胖和高血糖，然后用慢性皮下注射 NMU 进行治疗。每天记录体重和食物摄入量。注射14天后，进行腹腔葡萄糖耐量试验和18F-氟脱氧葡萄糖微正电子发射断层扫描/计算机断层扫描（18F-FDG micro-PET/CT）扫描。收集皮下 WAT (sWAT) 和肩胛间棕色脂肪组织，用于评估脂肪细胞大小、解偶联蛋白 1 ( Ucp1 ) 和其他产热相关基因的表达。提取皮下 WAT 的基质血管部分用于测量 2 型先天淋巴细胞 (ILC2s) 的比例。结果. 外周给药的 NMU 显着改善了葡萄糖耐量。Micro-PET/CT 表明 NMU 促进了 WAT 米色，苏木精和伊红 (H&E) 染色和免疫组织化学进一步证实了这一点。在饮食诱导的肥胖 (DIO) 小鼠中，NMU 激活了 WAT 中的产热相关基因。此外，NMU 刺激了 WAT 基质血管部分中的 ILC2。结论。总之，我们的研究表明，外周给药 NMU 是促进 WAT 米色和改善葡萄糖耐量受损的潜在治疗策略。