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That New Year’s resolution to move more is one of the toughest to keep, and a group of scientists working with obese mice think they’re starting to understand why.

Rather than our sedentary lives causing weight gain, says Alexxai Kravitz, the National Institutes of Health neuroscientist who led the study, changes in brain chemistry after we start gaining weight blunt our capacity to move.

“Obese mice can move just fine,” says Kravitz, who published the work with his team on Thursday in Cell Metabolism.


They just don’t.

What Kravitz and his crew found is that the activity of a particular dopamine receptor linked to movement goes down as mice gain weight on a high-fat diet. So the mice slow down and they move less. And when the researchers restored the activity of that dopamine receptor — DR2 — the mice started moving more, even though they were still obese.


The team also saw that lean mice missing the DR2 receptor acted like their obese buddies — they didn’t move around as much.

This is the therapeutic target, says Kravitz — restoring that dopamine receptor function.

“Maybe 20 or 30 years down the road, we could do that in people,” he says.

And one more thing: The scientists fed normal mice and the DR2-deficient mice the same high-fat diet. Both sets of mice gained weight at the same rate.

Kravitz says this is important because DR2 mutant mice move less from the get-go, whereas a normal mouse takes a little time to start seeing that dopamine receptor-related loss of exercise. The ability to exercise seems to be disconnected from weight gain, he says.

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

Still, before you abandon your New Year’s exercise resolution, keep in mind that this study was done using a high-fat diet, and not the normal calorie restriction that people (try valiantly to) maintain when they diet. The fat in the high-fat diet could be what’s tamping down DR2, not the weight gain the mice see.

That’s a big drawback to the work, says Vicki Vieira-Potter, a University of Missouri physiologist not involved in the study.

“So they feed the mice this high-fat diet, it impairs the receptor, and that decreases activity. A high-fat diet is a nice way to induce obesity, but it’s not the same as obesity,” she says.

She also says that a lot of the weight gain in the mice came after they stopped moving around, which indicates that the loss of movement did impact obesity.

“To call inactivity a consequence and not a cause of obesity is a broad misreading of what their research shows,” she says.

Still, she is excited about this: A high-fat diet affects the body, but it also affects the brain, via dopamine signaling, and thus, it’s likely to affect behavior.

Update: The photo with this story has been changed because the original was a hamster instead of a mouse.


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