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http://itsthewooo.blogspot.ca/2017/...t-dopamine.html
Went to this article through the Scribblepad blog;
https://www.sciencedaily.com/releas...61229141901.htm

Quote:

Inactivity in obese mice linked to a decreased motivation to move

Lol at that title. Maybe the freaky thing here is that people not seeing the obvious actually makes this a meaninful statement instead of a truism. Comes down to the definition of "motivation" as a neurological/metabolic trait rather than a character/moral trait.

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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.

"We 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 dopamine systems.

"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 inactivity?"

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.

The 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 postdoctoral fellow.

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.

"In 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.

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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.

This seems to conflict with other studies where animals fed similar high-fat diets were protected from weight gain by voluntary exercise. Those studies use running wheels vs. no running wheels. But maybe this is another sort of resistance. Rodents enjoy running wheels, it might be more fun than plodding about the cage. Comparable to somebody needing to overcome food reward resistance with less subtle flavours, maybe it takes more pleasurable activity to tempt the animals to get moving.

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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.

This thread is long enough that I don't remember if I've mentioned this, though I probably have. There are studies with low-palatability food, with obese rodents and humans. Lean subjects tend to eat to maintenance, obese undereat and lose weight. So there's a parallel here, an actual lowered motivation for both food and exercise that might be gotten past with food or activity that gives a stronger signal. You could look at this as calories in/calories out, increased intake of more palatable foods, decreased exercise.

Sweet sensitivity is sometimes used as a measure of depression in animals, a given concentration of sugar will taste less sweet if the animal is depressed. At least, that's the assumption. Pure candy will still taste sweet. So a depressed person might not appreciate an apple, but might like ice cream. Classical depression came with a decrease in appetite and weight loss, today it's often looked at as causing weight gain--if the only foods you're capable of enjoying are fattening, it's pretty likely that you'll get fatter. Interesting to think how antidepressants that are fattening might fit into this.