Diabetes and Obesity Center, Department of Medicine, Division of Environmental Medicine, Christina Lee Brown Envirome Institute, University of Louisville, Louisville, KY 40202, USA; Department of Physiology, University of Louisville, Louisville, KY 40202, USA.
Diabetes and Obesity Center, Department of Medicine, Division of Environmental Medicine, Christina Lee Brown Envirome Institute, University of Louisville, Louisville, KY 40202, USA.
J Sport Health Sci. 2022 Jul;11(4):479-494. doi: 10.1016/j.jshs.2022.06.001. Epub 2022 Jun 7.
Although the structural and functional effects of exercise on the heart are well established, the metabolic changes that occur in the heart during and after exercise remain unclear. In this study, we used metabolomics to assess time-dependent changes in the murine cardiac metabolome following 1 session of treadmill exercise. After the exercise bout, we also recorded blood lactate, glucose, and ketone body levels and measured cardiac mitochondrial respiration. In both male and female mice, moderate- and high-intensity exercise acutely increased blood lactate levels. In both sexes, low- and moderate-intensity exercise augmented circulating 3-hydroxybutryrate levels immediately after the exercise bout; however, only in female mice did high-intensity exercise increase 3-hydroxybutyrate levels, with significant increases occurring 1 h after the exercise session. Untargeted metabolomics analyses of sedentary female and male hearts suggest considerable sex-dependent differences in basal cardiac metabolite levels, with female hearts characterized by higher levels of pantothenate, pyridoxamine, homoarginine, tryptophan, and several glycerophospholipid and sphingomyelin species and lower levels of numerous metabolites, including acetyl coenzyme A, glucuronate, gulonate, hydroxyproline, prolyl-hydroxyproline, carnosine, anserine, and carnitinylated and glycinated species, as compared with male hearts. Immediately after a bout of treadmill exercise, both male and female hearts had higher levels of corticosterone; however, female mice showed more extensive exercise-induced changes in the cardiac metabolome, characterized by significant, time-dependent changes in amino acids (e.g., serine, alanine, tyrosine, tryptophan, branched-chain amino acids) and the ketone body 3-hydroxybutyrate. Results from experiments using isolated cardiac mitochondria suggest that high-intensity treadmill exercise does not acutely affect respiration or mitochondrial coupling; however, female cardiac mitochondria demonstrate generally higher adenosine diphosphate sensitivity compared with male cardiac mitochondria. Collectively, these findings in mice reveal key sex-dependent differences in cardiac metabolism and suggest that the metabolic network in the female heart is more responsive to physiological stress caused by exercise.
虽然运动对心脏的结构和功能影响已得到充分证实，但运动过程中心脏发生的代谢变化仍不清楚。在这项研究中，我们使用代谢组学来评估小鼠心脏代谢组在 1 次跑步机运动后的时间依赖性变化。运动后，我们还记录了血液中的乳酸、葡萄糖和酮体水平，并测量了心脏线粒体呼吸。在雄性和雌性小鼠中，中等强度和高强度运动都能使血液中的乳酸水平急性升高。在两性中，低强度和中等强度运动都能使运动后即刻的循环中 3-羟丁酸水平升高；然而，只有在雌性小鼠中，高强度运动增加了 3-羟丁酸水平，且在运动后 1 小时后出现显著升高。对安静状态下的雌性和雄性小鼠心脏进行非靶向代谢组学分析表明，在基础心脏代谢物水平上存在相当大的性别依赖性差异，雌性心脏的特征是泛酸、吡哆胺、同型精氨酸、色氨酸和几种甘油磷脂和神经鞘磷脂种类的水平较高，而乙酰辅酶 A、葡萄糖醛酸、古洛糖酸、羟脯氨酸、脯氨酰-羟脯氨酸、肌肽、鹅肌肽和肉碱化和糖基化种类的水平较低，与雄性心脏相比。在跑步机运动后，雄性和雌性心脏的皮质酮水平都升高；然而，雌性小鼠的心脏代谢组在运动诱导下发生了更广泛的变化，其特征是氨基酸（如丝氨酸、丙氨酸、酪氨酸、色氨酸、支链氨基酸）和酮体 3-羟丁酸的水平发生了显著的、随时间变化的变化。使用分离的心脏线粒体进行的实验结果表明，高强度跑步机运动不会急性影响呼吸或线粒体偶联；然而，雌性心脏线粒体的腺苷二磷酸敏感性普遍高于雄性心脏线粒体。总之，这些在小鼠中的发现揭示了心脏代谢中关键的性别依赖性差异，并表明女性心脏的代谢网络对运动引起的生理应激更敏感。
