Scientists Discover Link Between Brain and Weight Gain

How does a high-fat diet affect your brain?

Researchers from Canada's Memorial University have identified an inflammatory pathway in the brain linking high-fat diets to the activation of appetite-promoting neurons.

"Scientists have known for a while that high-fat foods cause a low-intensity inflammation in the brain," Lisa Fang, the study's first author, told Newsweek.

This inflammation is particularly seen in the hypothalamus, a region of the brain involved in maintaining balance within the body, including appetite regulation.

However, inflammation in this same area has also been associated with sickness-induced weight loss. So how can this inflammation cause both weight loss and weight gain?

First, it's necessary to understand how the hypothalamus regulates the body's energy balance. One of the key neurons involved in this system is called the melanin-concentrating hormone neuron. From their name, you would be forgiven for assuming that MCH neurons were related to skin color and eye pigmentation. But their role actually has a lot more to do with the body's energy balance.

"Melanin-concentrating hormone was originally discovered in fish as a hormone that concentrates melanin in the skin, hence changing the skin color," Fang said. "In mammals, melanin-concentrating hormone is found in cells in the brain and is most well known to regulate body weight. Specifically, MCH increases food intake and decreases energy expenditure, overall promoting weight gain.

"Some other important roles of MCH in the brain are promoting sleep, as well as regulating mood and memory," Fang said.

What Fang and her team discovered was that these neurons could be activated by inflammatory molecules called prostaglandins, or PGE2.

"PGE2 has a well-described role in fever and sickness behavior, including loss of appetite, so it was surprising that this appetite-reducing molecule also had an appetite-promoting role," Fang said.

The team also found that a high-fat Western diet stimulated the production of these inflammatory molecules. So how do these molecules trigger both weight loss and weight gain?

It all comes down to their concentration. At low concentrations, PGE2 activates those MCH neurons, while at higher concentrations it has been shown to inhibit them. High-fat diets have been shown to cause only low-intensity inflammation, which could explain why they are associated with increased appetite and weight gain. By contrast, inflammatory diseases induce much higher concentrations of PGE2 and thus weight loss.

To test the involvement of this inflammatory molecule in weight gain and neuron activation, the researchers genetically engineered a group of male and female mice to lack the receptors that interact with PGE2. As expected, mice on a high-fat diet that lacked these receptors displayed a lower energy intake, less weight gain and less liver fat accumulation.

This study, which was published in the journal Proceedings of the National Academy of Science on July 17, provides important insights for future obesity treatments.

"Our study supports the growing body of evidence that inflammation plays a key role in obesity, suggesting that diets and treatments with anti-inflammatory effects would be effective," Fang said.

She hopes her team's findings will help inform new therapies for obesity, saying, "Treatments that specifically block the mechanism found in our study can be expected to have an anti-obesity effect."

However, she added that it is important to be "as specific as possible when trying to target this mechanism since PGE2 has other functions in the brain as well as in other tissues in the body. It is critical to identify potential side effects and thoroughly test its safety before it can be used as a treatment."