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Scientists believe they are one step closer to developing medication that can mimic the effects of cardio in the body. This ‘cardio pill’ could make the health benefits of activities like running accessible to people who are physically unable to exercise enough.
Cardio Pill
Working on your health is much easier when you’re already healthy. However, if you have severe obesity or become immobile due to old age, getting enough exercise becomes more necessary but also more difficult. As a fitness enthusiast, this naturally sounds like sacrilege, but the health of millions of people worldwide could benefit if a pill could produce the effects of cardio safely. Nobody wants a new Stacker-gate, of course.
Previous work identified the operation of a genetic network activated during running. Researchers from the Salk Institute built on this and have now discovered how to activate this operation with a chemical substance[1,2].
It’s well known that people can improve their aerobic endurance through training…The question for us was: how does endurance work? And if we really understand the science, can we replace training with a drug?
Ronald Evans, Howard Hughes Medical Institute
Cardiovascular training aims to improve the heart and circulatory system, leading to better endurance. The researchers explain that as people become fitter, muscles start burning more fats and fewer carbohydrates. According to the researchers, endurance should therefore be expressed in the body’s ability to burn fat.
I don’t fully follow this line of thought because I miss, for example, the role of maximal oxygen intake. The heart’s ability to deliver more blood, glucose, and oxygen to the muscles. However, this does not make the developments from the lab any less interesting.
The earlier work involved research by Evans Lab into a genetic network called PPAR delta (PPARD). Mice genetically manipulated to keep this network continuously active were able to cover long distances, did not develop obesity, and were highly sensitive to insulin. All characteristics of good health. They also discovered that a substance called GW1516 also activated the genetic network PPARD. A dose of GW1516 led to the same effects on weight and insulin sensitivity. However, endurance did not increase.
Although this is already a very desirable effect, the researchers at Salk continued their research. They gave normal mice a higher dose of GW1516 and for a longer period (8 weeks instead of 4). The mice were normally inactive but were now given a fitness test. The mice given GW1516 could run for 270 minutes, while mice that did not receive GW1516 could only run for 160 minutes. A difference of 70%.
In both cases, exhaustion began when blood sugar levels dropped to 70mg/dl, suggesting that low blood sugar is the cause of fatigue.
To understand what happened at the molecular level, the researchers compared gene expression in a large muscle group of the mice. They found 975 genes that responded to the administration of GW1516. Some were activated, others suppressed. Genes that became more active are associated with higher fat burning. Surprisingly, the genes that increase carbohydrate burning were suppressed. Thus, a shift from carbohydrate to fat burning was caused. The researchers suspect that this occurs as a mechanism to save sugars for the brain.
The experimental drug did not mimic all the effects of cardio training. For example, the number of mitochondria (energy factories) in the muscle cell and the number of blood vessels did not increase. Additionally, the type of muscle fibers that burn fat did not increase compared to the muscle fiber types that mainly burn sugars. This would indicate that these muscle adaptations are not (fully) responsible for improving fitness.
“Exercise activates PPARD, but we’re showing that you can do the same thing without mechanical training. It means you can improve endurance to the equivalent level as someone in training, without all of the physical effort,”
Weiwei Fan, Salk Institute
The effects of cardio without the training. Pharmaceutical companies are now interested in developing clinical studies for humans.
References
- Weiwei Fan, Wanda Waizenegger, Chun Shi Lin, Vincenzo Sorrentino, Ming-Xiao He, Christopher E. Wall, Hao Li, Christopher Liddle, Ruth T. Yu, Annette R. Atkins, Johan Auwerx, Michael Downes, Ronald M. Evans. PPARδ Promotes Running Endurance by Preserving Glucose. Cell Metabolism, 2017; 25 (5): 1186 DOI: 10.1016/j.cmet.2017.04.006
- Cell Metabolism on May 2, 2017
