Scimex: Starting a regular program at the gym is a common New Year's resolution, but it's one that most people are unable to stick with for very long. Now a study done in mice is providing clues about one of the reasons why it may be hard for so many people to stick with an exercise program. The investigators found that in obese mice, physical inactivity results from altered dopamine receptors rather than excess body weight. The report appears in Cell Metabolism on December 29.
know that physical activity is linked to overall good health, but not
much is known about why people or animals with obesity are less active,"
says the study's senior author Alexxai V. Kravitz, an investigator in
the Diabetes, Endocrinology, and Obesity Branch at the National
Institute of Diabetes and Digestive and Kidney Diseases--part of the
National Institutes of Health. "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 has a background in studying
Parkinson's disease, and when he began conducting obesity research a few
years ago, he was struck by similarities in behavior between obese mice
and Parkinsonian mice. Based on that observation, he hypothesized that
the reason the mice were inactive was due to dysfunction in their
"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," Kravitz says. "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
In the study, mice were fed either a standard or a
high-fat diet for 18 weeks. Beginning in the second week, the mice on
the unhealthy diet had higher body weight. By the fourth week, these
mice spent less time moving and got around much more slowly when they
did move. Surprisingly, the mice on high-fat diet moved less before they
gained the majority of the weight, suggesting that the excess weight
alone was not responsible for the reduced movements.
investigators looked at six different components in the dopamine
signaling pathway and found that the obese, inactive mice had deficits
in the D2 dopamine receptor. "There are probably other factors involved
as well, but the deficit in D2 is sufficient to explain the lack of
activity," says Danielle Friend, first author and former NIDDK
The team also studied the connection between
inactivity and weight gain, to determine if it was causative. By
studying lean mice that were engineered to have the same defect in the
D2 receptor, they found that those mice did not gain weight more readily
on a high-fat diet, despite their lack of inactivity, suggesting that
weight gain was compounded once the mice start moving less.
many cases, willpower is invoked as a way to modify
behavior," Kravitz says. "But if we don't understand the underlying
physical basis for that behavior, it's difficult to say that willpower
alone can solve it."
He adds that if we begin to decipher the
physiological causes for why people with obesity are less active, it may
also help reduce some of the stigma that they face. Future research
will focus on how unhealthy eating affects dopamine signaling. The
researchers also plan to look at how quickly the mice recover to normal
activity levels once they begin eating a healthy diet and losing weight.