Fat fighters: NIH discovery in mice could lead to new drugs

Researchers from the National Institutes of Health (NIH) have identified an enzyme that could help in the fight against mid-life obesity and fitness loss. The findings have been published in Cell Metabolism.

Led by Jay H. Chung (head of the Laboratory of Obesity and Aging Research at the National Heart, Lung and Blood Institute, part of NIH), the team used mice models to analyse the role of an enzyme in obesity and exercise capacity. He explained that an overactive enzyme drives the genetic programme that promotes weight gain and loss of exercise capacity at mid-life.

Puzzled by the ageing-weight gain paradox, the researchers aimed to better understand why it is common to see weight gain and lowered exercise capacity in mid-life. Searching for biochemical changes that occurred in middle-aged animals they found an enzyme called DNA-dependent protein kinase, or DNA-PK, which increases activity with age. Further analysis demonstrated that this enzyme promotes the conversion of nutrients to fat and decreases the number of mitochondria.

“Our studies indicate that DNA-PK is one of the drivers of the metabolic and fitness decline that occurs during ageing, which makes staying lean and physically fit difficult and increases susceptibly to metabolic diseases like diabetes,” stated Chung. “The identification of this new mechanism is very important for improving public health. The study opens the door to the development of a new type of weight-loss medication that could work by inhibiting DNA-PK activity.”

However, the researchers stressed that these results need to be demonstrated in humans and people should continue to lower calorie intake and boost exercise to fight obesity.