糖异生
褐色脂肪组织
内分泌学
生物
内科学
内分泌系统
葡萄糖稳态
平衡
产热
碳水化合物代谢
脂肪组织
细胞生物学
新陈代谢
胰岛素
医学
胰岛素抵抗
激素
作者
Junqiang Xu,Le Chen,Jiaqi Wang,Shasha Zheng,Huahua Zhang,Sha‐Sha Ke,Xiaodan Cao,Yanteng Shi,Jing Li,Ke Zen,António Vidal-Puig,Chen-Yu Zhang,Liang Li,Xiaohong Jiang
标识
DOI:10.1038/s41467-023-41160-6
摘要
Abstract During cold exposure, activated brown adipose tissue (BAT) takes up a large amount of circulating glucose to fuel non-shivering thermogenesis and defend against hypothermia. However, little is known about the endocrine function of BAT controlling glucose homoeostasis under this thermoregulatory challenge. Here, we show that in male mice, activated BAT-derived extracellular vesicles (BDEVs) reprogram systemic glucose metabolism by promoting hepatic gluconeogenesis during cold stress. Cold exposure facilitates the selective packaging of miR-378a-3p—one of the BAT-enriched miRNAs—into EVs and delivery into the liver. BAT-derived miR-378a-3p enhances gluconeogenesis by targeting p110α. miR-378 KO mice display reduced hepatic gluconeogenesis during cold exposure, while restoration of miR-378a-3p in iBAT induces the expression of gluconeogenic genes in the liver. These findings provide a mechanistic understanding of BDEV-miRNA as stress-induced batokine to coordinate systemic glucose homoeostasis. This miR-378a-3p-mediated interorgan communication highlights a novel endocrine function of BAT in preventing hypoglycemia during cold stress.
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