Liver mitochondria play a central role in metabolic adaptations to changing nutritional states, yet their dynamic regulation upon anticipated changes in nutrient availability has remained unaddressed. Here, we found that sensory food perception rapidly induced mitochondrial fragmentation in the liver through protein kinase B/AKT (AKT)–dependent phosphorylation of serine 131 of the mitochondrial fission factor (MFFS131). This response was mediated by activation of hypothalamic pro-opiomelanocortin (POMC)–expressing neurons. A nonphosphorylatable MFF S131G knock-in mutation abrogated AKT-induced mitochondrial fragmentation in vitro. In vivo, MFF S131G knock-in mice displayed altered liver mitochondrial dynamics and impaired insulin-stimulated suppression of hepatic glucose production. Thus, rapid activation of a hypothalamus–liver axis can adapt mitochondrial function to anticipated changes of nutritional state in control of hepatic glucose metabolism.

中文翻译：

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食物感知促进肝脏中 MFFS131 的磷酸化和线粒体断裂

肝脏线粒体在适应不断变化的营养状态的代谢适应中发挥着核心作用，但它们对营养可用性预期变化的动态调节仍未得到解决。在这里，我们发现，食物的感官感知通过线粒体裂变因子 (MFFS131)​​ 丝氨酸 131 的蛋白激酶 B/AKT (AKT) 依赖性磷酸化迅速诱导肝脏中线粒体断裂。这种反应是由下丘脑表达阿片黑皮质素原（POMC）的神经元激活介导的。不可磷酸化的 MFFS131G敲入突变在体外消除了 AKT 诱导的线粒体断裂。体内，MFFS131G基因敲入小鼠表现出肝脏线粒体动力学改变和胰岛素刺激的肝葡萄糖产生抑制受损。因此，下丘脑-肝轴的快速激活可以使线粒体功能适应营养状态的预期变化，从而控制肝葡萄糖代谢。