近日，德国马克斯-普朗克代谢研究所Jens C. Brüning及其研究组发现，食物感知促进肝脏中MFFS131的磷酸化和线粒体碎片化。相关论文于2024年4月26日发表于国际学术期刊《科学》。

研究人员发现感官食物的知觉通过蛋白激酶B/AKT（AKT）依赖的，线粒体分裂因子（MFFS131）丝氨酸131磷酸化迅速诱导肝脏线粒体碎裂。这种反应是通过激活下丘脑表达阿片促黑素细胞皮质激素原（POMC）的神经元所介导。在体外，非磷酸化的MFFS131G基因敲入突变会减弱AKT诱导的线粒体碎片化。

在体内，MFFS131G基因敲入小鼠显示出肝脏线粒体动力学的改变，以及胰岛素刺激下抑制肝脏葡萄糖产生的功能受损。因此，快速激活下丘脑-肝脏轴可使线粒体功能适应预期的营养状态变化，从而控制肝脏葡萄糖代谢。

据介绍，肝脏线粒体在适应不断变化的营养状态的新陈代谢过程中发挥着核心作用，但它们在营养供应预期变化时的动态调节问题仍未得到解决。

附：英文原文

Title: Food perception promotes phosphorylation of MFFS131 and mitochondrial fragmentation in liver

Author: Sinika Henschke, Hendrik Nolte, Judith Magoley, Tatjana Kleele, Claus Brandt, A. Christine Hausen, Claudia M. Wunderlich, Corinna A. Bauder, Philipp Aschauer, Suliana Manley, Thomas Langer, F. Thomas Wunderlich, Jens C. Brüning

Issue&Volume: 2024-04-26

Abstract: 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 MFFS131G knock-in mutation abrogated AKT-induced mitochondrial fragmentation in vitro. In vivo, MFFS131G 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.

DOI: adk1005

Source: https://www.science.org/doi/10.1126/science.adk1005