Research ArticleExercise and Metabolism

Metabolic Signatures of Exercise in Human Plasma

Science Translational Medicine  26 May 2010:
Vol. 2, Issue 33, pp. 33ra37
DOI: 10.1126/scitranslmed.3001006

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What Happens When You Run the Boston Marathon?

We used to call it toil; now, we call it exercise. The human body has evolved to perform physical labor, and modern sedentary lifestyles are at odds with this evolutionary mandate. This disconnect makes it all the more imperative that we understand the physiology of how the body converts fuel to work. Lewis and colleagues have moved us toward that goal by comprehensively surveying blood metabolites in people of varying fitness levels before and during exercise. Through the use of a high-sensitivity mass spectrometry method, they have characterized these exercise-induced metabolic changes in unprecedented detail.

The authors measured 200 blood metabolites in groups of people before, during, and after exercise on a treadmill. They found that the elevated glycolysis, lipolysis, and amino acid catabolism that occur in skeletal muscle cells during use are reflected in a rise in marker metabolites of these processes in blood. Also appearing in the blood after exercise were niacinamide, which enhances insulin release and improves glycemic control, and allantoin, an indicator of oxidative stress. Even when other variables were controlled for, the people who were more fit—as measured by their maximum oxygen use—exhibited more lipolysis during exercise (98% increase) than did the less fit (48% increase) participants or those who developed heart ischemia upon exertion (18% increase). Even more striking was the increase in lipolysis (1128%) in runners after they finished the Boston Marathon, a 26.2-mile run through the winding roads of Boston and its environs. From these data, the authors could not tell whether the more well-conditioned individuals were fitter because their metabolism used fat more effectively or whether, once attaining fitness, these able-bodied metabolic systems were better at burning fat. A mechanistic clue is provided by a final experiment in which the authors show that a combination of six of the metabolites elevated by exercise reflects an increase in glucose utilization and lipid metabolism in skeletal muscle cells, whereas none of the individual elevated molecules signal this effect.

Thus, a cost of our sedentary lives may be to deoptimize the operation of the complicated system that is human metabolism. Sorting out how this backsliding occurs and how to restore the vigor of our metabolism will be facilitated by the findings and tools reported here.


  • Citation: G. D. Lewis, L. Farrell, M. J. Wood, M. Martinovic, Z. Arany, G. C. Rowe, A. Souza, S. Cheng, E. L. McCabe, E. Yang, X. Shi, R. Deo, F. P. Roth, A. Asnani, E. P. Rhee, D. M. Systrom, M. J. Semigran, R. S. Vasan, S. A. Carr, T. J. Wang, M. S. Sabatine, C. B. Clish, R. E. Gerszten, Metabolic signatures of exercise in human plasma. Sci. Transl. Med. 2, 33ra37 (2010).