A pill that can make people as “super fit” as highly-trained athletes without moving a muscle is a step closer to reality, researchers say.
They have discovered a protein, which can make muscles store and burn sugars at rates that vastly improve physical performance.
According to Daniel P. Kelly and his team at the Sanford-Burnham’s Lake Nona campus in Orlando, Fla., muscle performance and fitness are partly determined by how well your muscle cells use sugar as a fuel source.
In turn, exercising improves the muscle’s ability to take up sugars from the bloodstream and burn them for energy. On the flip side, conditions that reduce physical activity like obesity or chronic disease reduce the muscle’s capacity to burn sugar.
When activated in mice, the suggested metabolic re-programming dramatically improves exercise performance, and the new study reveals new targets that could be explored to increase the ability of muscles to burn sugars, an avenue that could ultimately lead to new prevention or treatment methods for obesity, metabolic syndrome, and diabetes.
“Essentially, these transgenic mice are capable of storing and burning sugars at rates usually only seen in the trained athlete. This allows for supranormal athletic performance,” Kelly said.
Kelly’s mice are special because they’re engineered to produce the protein PPARß/d in their muscle tissue, which is a nuclear receptor, a type of protein that binds DNA to turn genes on or off in response to outside signals, in this case, genes specific to muscle metabolism.
Kelly and his team also found that PPARß/d mice are super fit. Compared to normal mice, they ran longer and faster yet generated lower amounts of lactic acid, considered the chief mediator of exercise-induced muscle pain.
It turns out that exercise stimulates cells to assemble a complex of three proteins, PPARß/d, a protein that maintains cellular energy balance (adenosine monophosphate-activated protein kinase or AMPK), and a protein that helps activate muscle-specific genes (MEF2A).
Together, these proteins switch on the gene that produces lactate dehydrogenase, an enzyme that directs sugar-derived metabolites into mitochondria, where complete burning of the fuel is possible — effectively converting sugar to energy. It’s likely that this novel mechanism helps activate other genes involved in muscle fitness as well.
“Given the association of obesity and insulin resistance with diets enriched in simple sugars, we find these results promising as a step towards new therapeutics,” he said.
“Previously, members of the PPAR protein family have proven to be difficult drug targets due to the wide variety of effects they have in a cell. However, the findings in this study suggest that strategies for activating only a subset of events downstream of PPARß/d are possible. This could lead to favourable metabolic effects on muscle and other tissues,” he added.
The study has been published in the journal Genes and Development.