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Blocking protein may turn bad fat brown

Researchers working with mice may have found a way to convert “bad” white fat—which hoards calories, contributing to weight gain and obesity—into “good” brown fat—which actually helps burn calories.

The findings raise the prospect of developing more effective treatments, in people, for obesity and diabetes related to weight gain.

White fat stores calories and pads our bellies, hips, and thighs. In contrast, brown fat, found near our necks and shoulders, burns calories through a process that generates heat.

Listen to Irfan J. Lodhi discuss the research:

The researchers found that blocking the activity of a specific protein in white fat triggered the fat to begin to brown into beige fat, a type of fat in between white and brown. Blocking the protein to create beige fat caused the fat cells to heat up and burn calories.

“Our goal is to find a way to treat or prevent obesity,” says first author Irfan J. Lodhi, assistant professor of medicine in the endocrinology, metabolism, and lipid research division at Washington University in St. Louis. “Our research suggests that by targeting a protein in white fat, we can convert bad fat into a type of fat that fights obesity.”

Beige fat was discovered in adult humans in 2015. Though it is almost like an intermediary between white fat and brown fat, Lodhi says it functions more like brown fat and can protect against obesity.

PexRAP beige fat - between white and brown fat
Working with mice, researchers have identified a way to convert white fat, which stores calories, into brown fat that burns them. Above are white fat cells from a normal mouse (left) and from a mouse lacking the PexRAP protein (right), which interferes with the conversion of calorie-storing fat cells into calorie-burning cells. The fat cells without PexRAP store fewer calories and look more like brown fat cells. (Credit: Irfan J. Lodhi/Washington University in St. Louis)

His team conducted a series of experiments in mice, creating a genetic strain of animals that didn’t make a key protein in their white fat cells. Those mice had more beige fat and were leaner than their littermates, even when they ate the same amount of food as other mice. They also burned more calories.

“Mice normally have very low levels of the protein, called PexRAP, in their brown fat,” he says. “When we put the mice into a cold environment, levels of the protein also decreased in white fat, allowing that fat to behave more like brown fat. Cold induces brown and beige fats to burn stored energy and produce heat.”

When Lodhi’s team blocked PexRAP in the animals, the mice converted white fat into beige fat that could burn calories.

More than two-thirds of adults in the United States are either overweight or obese. Some 30 million people have diabetes. These findings study suggest that if therapies could help convert their bad fat into good fat, those numbers might start to decline.

This enzyme controls body fat but we can’t just delete it

Lodhi says if the PexRAP protein could be blocked safely in white fat cells in humans, people might have an easier time losing weight.

“The challenge will be finding safe ways to do that without causing a person to overheat or develop a fever, but drug developers now have a good target,” he says.

The study appears in the journal Cell Reports.

National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (NIH) grants supported this work. Startup funds from the Washington University department of medicine and a Pilot & Feasibility Grant from the Washington University Diabetes Research Center provided additional funding. The China Scholarship Council provided additional support.

Source: Washington University in St. Louis

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