Couch potato sheds light on exercise and diabetes

Mice lacking in a protein coactivator maintain normal activity and body weight, but can’t seem to muster up the energy to exercise say American researchers.

The couch potato mouse is lacking PGC-1, a protein coactivator that muscles need to convert carbohydrate into energy. This is the first time PGC-1 has completely been removed from muscle tissue and provided Dr Daniel Kelly and colleagues at the Sanford-Burnham Medical Research Institute with the chance to unravel the protein’s role in muscle development, exercise and metabolism.

“Part of our interest in understanding the factors that allow muscles to exercise is the knowledge that whatever this machinery is, it becomes inactive in obesity, ageing, diabetes and other chronic conditions that affect mobility,” said Kelly.

Physical stimulation normally boosts PGC-1 activity and switches on genes that increase fuel storage – which leads to trained muscle. However, even though they looked and behaved normally, mice without the protein couldn’t run on a treadmill.

Mice lacking PGC-1 can’t convert fuel into energy – their mitochondria does not function properly and the cells have to work harder to stay vigorous. This extra effort rapidly depletes carbohydrate reserves, leading to premature fatigue. This suggests that PGC-1 is necessary for exercise, but not normal muscle development and activity.

The mice also responded normally to insulin, meaning they were not a risk for developing diabetes. This was unexpected as many scientists believed that dysfunctional mitochondria can trigger a cascade of insulin resistance and diabetes. The study suggests that malfunctioning mitochondria may be a result of diabetes rather than a cause.

“Lo and behold, even though these animals couldn’t run, they showed no evidence of insulin resistance,” Dr Kelly said, “We are now investigating what happens when we boost PGC-1 activity intermittently, as normally occurs when a person exercises.”