Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Biology, Stanford University, Stanford, CA 94305, USA; Sarafan ChEM-H, Stanford University, Stanford, CA 94305, USA.
Sarafan ChEM-H, Stanford University, Stanford, CA 94305, USA; Department of Chemistry, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Cell Metab. 2023 Jul 11;35(7):1261-1279.e11. doi: 10.1016/j.cmet.2023.04.011. Epub 2023 May 3.
There is a significant interest in identifying blood-borne factors that mediate tissue crosstalk and function as molecular effectors of physical activity. Although past studies have focused on an individual molecule or cell type, the organism-wide secretome response to physical activity has not been evaluated. Here, we use a cell-type-specific proteomic approach to generate a 21-cell-type, 10-tissue map of exercise training-regulated secretomes in mice. Our dataset identifies >200 exercise training-regulated cell-type-secreted protein pairs, the majority of which have not been previously reported. Pdgfra-cre-labeled secretomes were the most responsive to exercise training. Finally, we show anti-obesity, anti-diabetic, and exercise performance-enhancing activities for proteoforms of intracellular carboxylesterases whose secretion from the liver is induced by exercise training.
人们对于能够介导组织串扰并作为身体活动分子效应物的血液传播因子非常感兴趣。尽管过去的研究集中在单个分子或细胞类型上,但对于身体活动对整个生物体分泌组的反应尚未进行评估。在这里,我们使用细胞特异性蛋白质组学方法,生成了小鼠运动训练调节分泌组的 21 种细胞类型、10 种组织图谱。我们的数据集确定了 >200 个运动训练调节的细胞类型分泌的蛋白对,其中大多数以前没有报道过。Pdgfra-cre 标记的分泌组对运动训练的反应最敏感。最后,我们展示了细胞内羧酸酯酶的蛋白形式的抗肥胖、抗糖尿病和增强运动表现的作用,其从肝脏的分泌是由运动训练诱导的。