Mid-life obesity-driven enzyme identified

US researchers have said that they have identified an enzyme that may play a central role in the development of obesity in mid-life. They found that an enzyme called DNA-dependent protein kinase or DNA-PK increases in activity with age.

In two groups of mice being fed high-fat foods, those who received an inhibitor that blocked the enzyme had a 40 per cent decrease in weight gain, compared with those that did not get it.

The findings, published in the US journal Cell Metabolism, could upend current notions about why people gain weight as they age, and could one day lead to more effective weight-loss medications.

"Our society attributes the weight gain and lack of exercise at mid-life primarily to poor lifestyle choices and lack of will power, but the study shows that there is a genetic programme driven by an overactive enzyme that promotes weight gain and loss of exercise capacity," said lead author Jay H Chung, head of the Laboratory of Obesity and Aging Research at the National Heart, Lung and Blood Institute (NHLBI).

Researchers have known for years that losing weight and maintaining the capacity to exercise tend to get harder beginning between ages 30 to 40, the start of mid-life. Scientists have developed new therapies for obesity, including fat-fighting pills, but many of those therapies have failed.

Chung and his associates searched for biochemical changes that occurred in middle-aged animals that are equivalent to 45 years in humans. Further work showed that DNA-PK promotes conversion of nutrients to fat and decreases the number of mitochondria, tiny organelles in the cells that turn fat into energy to fuel the body.

Mitochondria can be found in abundance among young people, but the numbers drop considerably in older people. Researchers know that decreased mitochondria can promote obesity as well as loss of exercise capacity.

Chung and his associates theorised that reducing DNA-PK activity may decrease fat accumulation and increase mitochondria number as well as promote fat burning.

"The study opens the door to the development of a new type of weight-loss medication that could work by inhibiting DNA-PK activity," Chung said.
However, he noted that DNA-PK inhibitors have yet to be tested this way in humans.

In the meantime, the researchers said, middle-aged people who are fighting obesity should not abandon common practices of reducing calorie intake and boosting exercise, even if it takes a while to see results.