Muscle-Liver Substrate Fluxes in Exercising Humans and Potential Effects on Hepatic Metabolism
Muscle-Liver Substrate Fluxes in Exercising Humans and Potential Effects on Hepatic Metabolism
复制标题
人类运动中的肌肉-肝脏底物通量及其对肝脏代谢的潜在影响
DOI：
10.1210/clinem/dgz266
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发表时间：
2020-04-01
影响因子：
5.8
通讯作者：
Weigert, Cora
中科院分区：
文献类型：
--
作者：
Hu, Chunxiu;Hoene, Miriam;Weigert, Cora
背景：在运动过程中，肝脏对维持能量稳态至关重要。骨骼肌来源的代谢物可参与肝脏代谢的调节。目的：我们旨在阐明运动时哪些代谢产物从运动肌肉中释放并被肝脏吸收，以及它们对肝功能的潜在影响。方法：在两项独立的研究中，年轻的健康男性禁食一夜，然后进行急性运动。通过毛细管电泳和液相色谱-质谱代谢组学平台研究了肝-内脏床以及运动和休息腿上动脉-静脉代谢物的差异。通过通路分析分析运动小鼠的肝脏转录组数据，发现运动调节代谢产物和肝脏转录激活物之间可能存在重叠。结果：在运动过程中，肝脏O-2摄取和CO2输送增加了两倍。与所有其他游离脂肪酸（FFA）相比，那些具有18个或更多碳原子且高度饱和的游离脂肪酸在肝静脉中持续释放，只有轻微的运动变化。FFA 6:0和8:0从工作腿释放，并被肝移植床吸收。琥珀酸盐和苹果酸盐在运动中表现出明显的肝脏摄取，也从运动腿释放。运动小鼠肝脏的转录反应表明HIF-、NRF2-和camp依赖基因转录的激活。这些途径也可以被琥珀酸盐激活。结论：代谢产物在运动肌肉和肝脏之间循环，可能通过作为底物和信号分子支持代谢适应运动。
Context: The liver is crucial to maintain energy homeostasis during exercise. Skeletal muscle-derived metabolites can contribute to the regulation of hepatic metabolism.Objective: We aim to elucidate which metabolites are released from the working muscles and taken up by the liver in exercising humans and their potential influence on hepatic function.Methods: In two separate studies, young healthy men fasted overnight and then performed an acute bout of exercise. Arterial-to-venous differences of metabolites over the hepato-splanchnic bed and over the exercising and resting leg were investigated by capillary electrophoresis- and liquid chromatography-mass spectrometry metabolomics platforms. Liver transcriptome data of exercising mice were analyzed by pathway analysis to find a potential overlap between exercise-regulated metabolites and activators of hepatic transcription.Results: During exercise, hepatic O-2 uptake and CO2 delivery were increased two-fold. In contrast to all other free fatty acids (FFA), those FFA with 18 or more carbon atoms and a high degree of saturation showed a constant release in the liver vein and only minor changes by exercise. FFA 6:0 and 8:0 were released from the working leg and taken up by the hepatosplanchnic bed. Succinate and malate showed a pronounced hepatic uptake during exercise and were also released from the exercising leg. The transcriptional response in the liver of exercising mice indicates the activation of HIF-, NRF2-, and cAMP-dependent gene transcription. These pathways can also be activated by succinate.Conclusion: Metabolites circulate between working muscles and the liver and may support the metabolic adaption to exercise by acting both as substrates and as signaling molecules.