A chemical imbalance in the brain could be causing people to exercise less

It was a big meal.
It was a big meal.
Image: Reuters/Jason Lee
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It’s the time of the year when a lot of us start setting exercise goals in hopes of shedding some extra weight. The sad fact is, most of us will fail to get moving as much as we want.

Why might that be? Researchers at the National Institutes for Health (NIH) wanted to find an answer. They turned to the world’s easiest subject for such tests: mice.

Two groups of eight mice were fed either a normal diet or a high-fat diet. As predicted, the high-fat diet mice gained weight and also started moving less than those fed the normal diet. The researchers also found that the activity of a particular receptor associated with movement found in the brain called DR2 went down in obese mice while it stayed the same in others.

To researchers’ surprise, when they selectively activated the DR2 receptor using a drug, the obese mice started moving as much as the other mice. To be sure that their intervention wasn’t a fluke they repeated the experiment. This time, instead of activating DR2 in obese mice, they inactivated the DR2 receptor in lean mice. As expected, the lean mice started behaving like obese mice and stopped moving. The results were published in Cell Metabolism.

So it seems that obese mice really do have the ability to move, but a high-fat diet causes a chemical imbalance that kills their desire to do so. Could developing a drug to activate the DR2 receptor in humans then help us deal with the obesity crisis?

Not so fast. The NIH researchers did one more experiment to answer that question. They took two groups of eight mice and deactivated the DR2 receptor, leaving the other untouched. That meant one group was not moving and the other was moving normally. Then both were fed the same high-fat diet. In yet another surprise, both groups of mice gained weight at the same rate.

“Exercise is a healthy thing to do, but its impact on weight has been overstated,” lead researcher Alexxai Kravitz told Stat. “We have to be realistic about the size of the effect of exercise on weight, as opposed to health benefits.”

The conditions used in the study, such as a high-fat diet, aren’t strictly translatable to human behavior. So the conclusions cannot yet be directly applied to humans. But this is the first time we have found a biological explanation for the lack of physical activity among the obese, and the results will have an implication for humans in years to come.