美国西北大学Congcong He研究组发现，运动激活的肝脏自噬通过FN1-α5β1整合素途径驱动运动的代谢益处。2023年2月21日，《细胞—代谢》杂志在线发表了这项成果。

研究团队发现，肝脏自噬激活对于运动诱导的代谢益处至关重要。运动小鼠的血浆或血清足以激活细胞的自噬。通过蛋白质组学研究，研究人员确定了纤维连接蛋白（FN1），作为一种运动诱导的、分泌型自噬诱导循环因子，它以前被认为是一种细胞外基质蛋白。小鼠分泌的FN1通过肝脏受体α5β1整合素和下游IKKα/β-JNK1-BECN1通路介导运动诱导的肝脏自噬和全身胰岛素敏化。因此，研究人员证明了肝脏自噬激活通过肌肉分泌的可溶性FN1和肝脏α5β1整合素信号通路驱动运动诱导的糖尿病代谢益处。

据了解，目前尚不清楚运动是如何在肌肉组织和非收缩组织中引发系统性代谢益处的。自噬是应激诱导的溶酶体降解途径，介导蛋白质和细胞器的周转和代谢适应。运动不仅在收缩性的组织中激活自噬，而且在非收缩性的组织中也激活自噬，包括肝脏。然而，运动激活的自噬在非收缩组织中的作用和机制仍是一个谜。

附：英文原文

Title: Exercise-activated hepatic autophagy via the FN1-α5β1 integrin pathway drives metabolic benefits of exercise

Author: Kenta Kuramoto, Huijia Liang, Jung-Hwa Hong, Congcong He

Issue&Volume: 2023-02-21

Abstract: How exercise elicits systemic metabolic benefits in both muscles and non-contractiletissues is unclear. Autophagy is a stress-induced lysosomal degradation pathway thatmediates protein and organelle turnover and metabolic adaptation. Exercise activatesautophagy in not only contracting muscles but also non-contractile tissues includingthe liver. However, the role and mechanism of exercise-activated autophagy in non-contractiletissues remain mysterious. Here, we show that hepatic autophagy activation is essentialfor exercise-induced metabolic benefits. Plasma or serum from exercised mice is sufficientto activate autophagy in cells. By proteomic studies, we identify fibronectin (FN1),which was previously considered as an extracellular matrix protein, as an exercise-induced,muscle-secreted, autophagy-inducing circulating factor. Muscle-secreted FN1 mediatesexercise-induced hepatic autophagy and systemic insulin sensitization via the hepaticreceptor α5β1 integrin and the downstream IKKα/β-JNK1-BECN1 pathway. Thus, we demonstratethat hepatic autophagy activation drives exercise-induced metabolic benefits againstdiabetes via muscle-secreted soluble FN1 and hepatic α5β1 integrin signaling.

DOI: 10.1016/j.cmet.2023.01.011

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00011-6