Using gravity to help us understand the AMPK-PGC-1α axis in skeletal muscle from healthy young males
The mitochondrion is a critical component of the cell and is responsible for producing energy needed by our bodies. One way our body adapts to exercise is by enlarging and creating more mitochondria. A primary protein believed to be involved in regulating these exercise-induced mitochondrial changes is called peroxisome proliferator-activated gamma coactivator 1-alpha (PGC-1α). Generally, the harder someone exercises (i.e. higher exercise intensities), the more PGC-1α increases. There are also several proteins that ‘turn on’ or activate PGC-1α, and these too increase as exercise intensity goes up. This means exercise at a given intensity proportionately increases both PGC-1α and its activators. Consequently, it has been difficult for researchers to single out the impact of any one particular activator of PGC-1α on PGC-1α in human muscle. If researchers experimentally reduce blood flow to exercising muscle, it could help them understand the effect of a particular PGC-1α activator on PGC-1α because some activators should be sensitive to amounts of oxygen in our muscle cells. Specifically, because blood flow restricted (BFR) aerobic exercise should reduce the amount of oxygen in exercising muscle, the role of a particular oxygen-sensitive PGC-1α activator may be better understood by using BFR and non-BFR aerobic exercise protocols to compare amounts of PGC-1α produced. Matching the intensity of these two protocols is important because that way the non-oxygen-sensitive PGC-1α activators can remain unchanged while the oxygen sensitive one(s) should increase. Indeed, results from previous studies suggest that this may be the case, however these studies have two general limitations. First, the BFR models used in those studies are expensive and difficult to build. Second, these studies were conducted in a way that leaves them vulnerable to the influence of bias; bias matters because it may lead to potentially incorrect results and interpretations. Minimizing bias is an essential aspect of good research. Therefore, we developed an inexpensive BFR model that uses gravity to reduce muscle oxygenation, and we used experimental best practices to test our hypothesis that our BFR model would increase both PGC-1α and its oxygen-sensitive activator more than intensity-matched non-BFR aerobic exercise. Our results supported this hypothesis.