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White fat in mice can be forced to burn energy like brown fat by flipping a molecular switch

The technique could be used to help prevent weight gain in humans

NYU

Scientists say they have figured out a way to make white fat cells in mice burn energy — just by flipping a molecular switch. If this mechanism works similarly in humans, it could open up new ways to help combat obesity.

There are two kinds of fat, white fat and brown fat, which is sometimes referred to as the "good" type of fat, because it burns calories rather than storing them like white fat does. The main purpose of brown fat is to help generate body heat. By turning a group of rodents' white fat cells into brown ones temporarily, the scientists prevented the mice from becoming obese while feeding the rodents a high-fat diet, according to a study published today in Cell Metabolism.

Brown fat is sometimes referred to as the "good" type of fat

For a long time, scientists thought brown fat didn’t exist in adult humans — until 2009, when researchers discovered that adult humans have stores of brown fat, too. Since then, efforts have focused on finding out if white fat can be converted to brown fat, in the hopes of developing drugs that may help people control their weight by increasing the number of calories people burn. Obesity, which affects more than a third of adults in the US, raises the risk of heart attack, stroke, and type 2 diabetes. Today’s study offers up a way to make white fat cells act like brown fat cells using a drug.

"Brown fat is not going to be the magic bullet to cure all forms of obesity," says Shingo Kajimura, a study author and assistant professor at the University of California-San Francisco. "But it could be a complementary way to increase energy expenditure."

Normally, mammals shiver when they get cold, producing kinetic energy in their muscles to heat things up. But mammals that can't shiver — such as hibernating animals and newborns — must rely more on their brown fat cells; the cold activates these cells, causing them to start burning energy in the body and generate heat — a process known as thermogenesis. "Brown fat is really about a defense mechanism against a cold environment," says Kajimura. But because it burns calories, activating brown fat results in weight loss, too.

Bears and babies are known to have higher amounts of brown fat to combat cold environments. (Mousse/Wikimedia Commons)

In today’s study, the research team simulated a cold environment for both brown fat cells and white fat cells, and then mapped out how the cells responded. They were surprised to find that an enzyme called casein kinase2, or CK2, is only activated in white fat — not brown fat — in response to cold. So the researchers blocked CK2 in a group of mice, by using a drug that specifically targets it. This caused the white fat cells to start burning calories, like brown cells do, when exposed to cold. And when the researchers blocked CK2 in mice on a high-fat diet, it stopped the animals from becoming obese while on a high-fat diet.

The findings could pave the way for a similar molecular switch to be flipped in humans. Of course, what works in mice doesn't always translate to a human model, so it's possible the enzyme won't work the same way in human clinical trials. Also, the researchers only showed that blocking CK2 prevents weight gain; there's no evidence that blocking the enzyme will stimulate weight loss.

White fat cells burned calories like brown cells

But if CK2 is shown to work similarly in humans, it's possible that a drug targeting the enzyme could be available relatively soon. The drug the researchers used to block CK2 is currently being tested in humans as an anti-tumor medication. (CK2 is known to be activated in certain types of cancer.) So far, this medication hasn't shown any harmful side effects in humans.

This study isn't the first to show that white fat can be manipulated to act like brown fat. However, it's the first to alter a molecular switch found inside white fat cells. "It's very intriguing," said Sheila Collins, an expert in metabolic diseases at the Sanford Burnham Prebys Medical Discovery Institute, who did not work on the study. "He’s looking at something that’s inside the cell — an enzyme that’s probably a part of an important cascade that pushes the cell to have all these brown fat characteristics."

Kajimure says the ultimate goal is not to find an easy solution for losing weight, but another tool that doctors can use to help those battling obesity and diabetes. By forcing white fat cells to burn energy for a little while, perhaps it can help people strike a better balance between the amount of energy they consume versus how much they expend.