With 2017 being ushered in on Saturday night, many will be making resolutions to get active and lose some weight, possibly not for the first time. A new study may provide clues as to why it is so difficult for overweight people to maintain the motivation to keep active. If our mice cousins are any guide, the cause may not be the extra physical effort required to shift that spare tire we're carrying, but the result of altered dopamine receptors in our brains.

The study was led by Alexxai V. Kravitz, an investigator in the Diabetes, Endocrinology, and Obesity Branch at the National Institute of Diabetes and Digestive and Kidney Diseases. Having a background in studying Parkinson's disease, Kravitz moved into obesity research a few years ago and was struck by similarities between mice with Parkinson's and obese mice. With that in mind, he wondered whether the inactivity of the obese mice could be due to problems with their dopamine systems.

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"Other studies have connected dopamine signaling defects to obesity, but most of them have looked at reward processing – how animals feel when they eat different foods," says Kravitz. "We looked at something simpler: dopamine is critical for movement, and obesity is associated with a lack of movement. Can problems with dopamine signaling alone explain the inactivity?"

To get some answers, the team split mice into two groups: the first group was fed a standard diet for 18 weeks, while the second was given a high-fat diet. Those in the second group had higher body weight by the start of the second week, and by the fourth week spent less time moving and moved more slowly when they did move. However, the team noticed the reduction in movement occurred before the mice had gained the majority of the weight, suggesting it was not the extra weight alone that was responsible for the increase in inactivity.

By looking at six different components in the dopamine signaling pathway, the researchers found deficits in the D2 dopamine receptor for the inactive mice. Although the researchers say other factors were likely involved, the deficit in the D2 dopamine receptor would be enough to explain the reduction in activity.

To ascertain whether the inactivity was the cause of the weight gain, the researchers also studied lean mice that were engineered to have the same D2 dopamine receptor deficit as the obese mice. They found that, despite their inactivity, these lean mice didn't gain weight as readily on a high-fat diet, which suggests that the weight gain was compounded when the mice became more inactive.

"There's a common belief that obese animals don't move as much because carrying extra body weight is physically disabling. But our findings suggest that assumption doesn't explain the whole story," Kravitz says. "In many cases, willpower is invoked as a way to modify behavior. But if we don't understand the underlying physical basis for that behavior, it's difficult to say that willpower alone can solve it."

In the quest to reveal the psychological causes behind why obese people are less active, which Kravitz believes could help reduce the stigma they face, the team will next examine how unhealthy eating affects dopamine signaling. They also plan to explore how long it takes for the mice to return to normal activity levels once they begin a healthy diet and start to lose weight.

The team's study appears in the journal Cell Metabolism.

Source: Cell Press via EurekAlert

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