Exercise Metabolism, Set 2

Leave all the afternoon for exercise and recreation, which are as necessary as reading. I will rather say more necessary because health is worth more than learning.—Thomas JeffersonTwo years ago, we successfully brought together leaders in the exercise field, including physiologists, clinicians, and molecular biologists, to promote cross-pollination of ideas for the first Cell Symposium on Exercise Metabolism in Amsterdam. When the time came to decide whether or not to repeat the meeting, the “yes” vote was unanimous. We again teamed up with Drs. Juleen Zierath and John Hawley for the second running of the Exercise Metabolism Cell Symposium, this time in Sweden, which has a long tradition in exercise physiology. This Special Issue of Cell Metabolism on the theme of exercise sets the stage for our upcoming symposium in May, starting with a unique cover featuring many of the Cell Symposium speakers and Cell Metabolism editors getting their heart rates up. Besides our Speaker and Editor Voices series, which blends personal stories and research inspiration, you will find a Crosstalk and a Perspective, as well as Reviews and research articles, on exercise.Although we all know that exercise is good for us, promotes healthy aging, improves cognitive function, and staves off a wide range of diseases, the WHO reports that physical inactivity ranks as the fourth leading risk factor for global mortality (http://www.who.int/dietphysicalactivity/pa/en/). In their Crosstalk opinion article, Gibala and Hawley underscore that lack of time is one of the main reasons for delaying going to the gym and discuss the idea that high-intensity interval training might be an effective way of addressing this conundrum. However, despite interval training gaining in popularity, the most effective protocol is still somewhat unclear, as are the underlying molecular mechanisms.In case you are wondering what exercise physiology is, Gabriel and Zierath define it as the “science of studying limits: the limits of elite performance, the limits of the health benefits of exercise, or the limits/barriers to achieving increased population-wide participation in exercise.” Their Perspective highlights how early investigations on the physiological limits of performance have set the stage for modern day exercise scientists to start unraveling the molecular mechanisms of exercise. Cardiac adaptation and fuel selection are, of course, important determinants of performance. Leinwand and colleagues compare an athlete’s physiological heart growth to the pathological hypertrophy observed with hypertension or ischemic heart disease, illustrating how exercise pathways can antagonize pathological pathways. Goodpaster and Sparks argue in their overview of metabolic flexibility in fuel selection that, while targeting metabolic inflexibility in diabetes and obesity is an attractive therapeutic option, “any pharmacologic strategy purporting to mimic exercise would need to impact metabolic flexibility and also induce increases in energy expenditure and demand similar to exercise. This should prove to be challenging, if not impossible.”As the molecular mechanisms underlying exercise emerge, the controversial topic of “exercise in a pill” often comes up. Contrary to Goodpaster’s view on exercise mimetics, a recent Perspective in our journal by Fan and Evans argues that exercise mimetics are already here and discusses their effects on health and as performance-enhancing drugs (Fan and Evans, 2017xFan, W. and Evans, R.M. Cell Metab. 2017; 25: 242–247Abstract | Full Text | Full Text PDF | PubMed | Scopus (3)See all ReferencesFan and Evans, 2017). While it is unlikely that targeting a single pathway would recapitulate the pleiotropic effects of exercise, PPARβ/δ and AMPK have been identified as promising candidates to boost the exercise response. In this issue, the Holloszy group details a two-step process through which PPARβ/δ mediates the adaptive skeletal muscle response to endurance exercise, with an initial early mitochondria maintenance phase, followed by long-term increased mitochondrial biogenesis. Taking advantage of the fact that PPARβ/δ can be pharmacologically targeted, the Evans group shows that PPARβ/δ plays a crucial role in glucose sparing and delays the onset of “hitting the wall,” with agonist-treated mice extending their running time by over 100 min. In turn, Miller and colleagues shed new light on tissue specificity of AMPK by employing a new small-molecule activator of AMPK, which results in a re-wiring of the muscle transcriptome and rapid lowering of glucose levels, independently of AMPK activation in the liver.As the field of exercise makes strides forward, now, more than ever, we need to keep the momentum of exercise research going to better our health. On the heels of the 121st Boston marathon, highlighting endurance, willpower, and perseverance, including the spectacular participation of Kathrine Switzer, the first woman to officially run the Boston Marathon 50 years ago, we could not agree more with Ruth Loos that “the world is a better place after a run.”