Battle of the Bulge May Mean Hormone Deficiency

Loss of the hormone orexin impairs brown fat function and promotes obesity in mice, according to researchers at Sanford-Burnham Medical Research Institute. Here, the leaner mouse with functional brown fat (left) dissipates considerable amounts of energy as heat. The orexin-deficient mouse (right) lacks the fat fuel fighter, storing energy as fat instead of burning it.

Overeating may not be the only cause of obesity. Researchers at Sanford-Burnham Medical Research Institute in Orlando, Fla., are reporting a link between the metabolism-stimulating hormone orexin and the calorie-burning ability of brown fat in mice – a finding that they believe could hold true for humans.

“We all know people who can eat whatever they want without bulking up,” said Devanjan Sikder, lead author and assistant professor of metabolic signaling and disease at Sanford-Burnham. “And then we know people who just look at cheese and get fat. The question is why?”

In a study released Tuesday, researchers said the answer might lie in the body’s levels of orexin, a hormone produced in the brain that plays a role in sleep cycles, metabolic rates and feelings of hunger.
The study will be published Wednesday in the journal “Cell Metabolism.”

“People who are overweight - even if they don’t eat excessive amounts of food - might be so because they lack the levels of orexin that are needed to activate brown fat and therefore burn calories,” Sikder said.

As opposed to white fat, which stores fat, said Shingo Kajimura, a cell and tissue biology professor at the University of California, San Francisco, brown fat is responsible for burning excess energy. It’s composed mostly of mitochondria, the power plants of a cell that are extremely efficient when it comes to converting calories into energy.

“It’s been seen that the leaner you are, the more brown fat you have,” said Kajimura.

Sikder explained that, when you take in excess calories or have a high fat diet, there’s normally an increase in energy expenditure for people with normal levels of orexin. But if you don’t have orexin, you can’t do this and the white fat stores all the extra calories.

To show the effects of orexin on the ability to burn calories, researchers at Sanford-Burnham studied mice over a six-week period. During this time, they fed a high-fat diet to mice that were genetically engineered to lack orexin and to those with normal levels of the hormone.

“What we found,” Sikder said, “was that the mice without orexin failed to up their energy expenditure, gaining weight, while the mice with orexin increased energy expenditure rate by 13 percent.”

This means that overeating was not the primary cause of the orexin-free mice’s obesity, he said. Rather, they lacked the hormone necessary to turn extra calories into energy by generating heat – a process known as thermogenesis.

As part of the experiment, researchers also gave the orexin-deficient mice a dose of the hormone.

According to their findings, the orexin caused the mice to develop brown fat and therefore burn excess energy at higher levels.

“The question now is can we fix this in humans? Can we control for this?" said Sikder. "Animal studies would predict that it might be possible to inject orexin into people to activate brown fat and make them leaner,” he said.

As opposed to current weight-loss drugs, which focus on suppressing a person’s appetite and can have psychological effects, Sikder said that increasing orexin levels could offer a new approach to treating obesity and other metabolic disorders.

“Orexin is an ideal candidate for preventing or treating obesity in humans,” he said.

So far, studies have only involved mice, but Sikder said Sanford-Burnham are in the process of being approved for a clinical trial involving humans, something he hopes will happen in the next three to five years.

Kajimura said he believes hormone therapy still has a ways to go before it can be tested on humans.

“But,” he said, “if researchers could find a way to convert white fat to brown fat, it would be instrumental in treating obesity.”


-Story by Jennifer Lazuta. Reprinted with permission from Medill News Service.

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