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Could HUMBLE Fat One Day Battle Obesity?

closeup of doctor's scale
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There are three types of fat in the human body: one is white, and the other two are brown. Researchers at the Joslin Diabetes Center (JDC) in Boston have offered proof of concept for a treatment that can turn one into the other, which may spell good news for weight loss.

White fat, or white adipose tissue, is what builds up in our bodies when we take in more energy than we burn. The body uses what it can, and the rest is packed on to our hips, bellies, butts, and pretty much everywhere else, to be stored for a later time. In the early time of human evolution, this adaptation allowed us to store energy and tap it when food ran scarce so that we could survive bad harvests or unsuccessful hunts. These days, it just makes it hard for us to fit into our clothes.

It also leads to obesity, which is the number one cause of type 2 diabetes.

Feel the Burn

Brown fat and human brown-like (HUMBLE) fat comprise the two other types of adipose tissue in the body. Unlike white fat, which stores energy, it burns energy. It gets its color from iron and is used by the body to warm us up before our shivering response kicks in. Babies have a lot of brown fat, but, by the time adulthood comes around, most of it is gone. Some research shows that it’s possible to turn white fat into brown through cold exposure, which is partly behind today’s cold-water plunging craze. In fact, one study showed that brown fat could be created by exposure to temperatures around 66°F for two hours. But dunking obese people into ice baths isn’t practical, so the researchers at JBC took a different approach.

Using a variation on the simple and popular gene-editing program known as CRISPR, they figured out that inducing white progenitor (pre-fat) cells to express a gene called UCP1 turned them into HUMBLE cells.

HUMBLE Mice

The cells were then implanted into mice. Those that received the HUMBLE cells gained less weight than mice given only white fat cells. What’s more, the HUMBLE mice had a greater ability to clear glucose from the blood, and they showed a greater sensitivity to insulin—both traits that are hampered in type 2 diabetes.

Not only did the white cells turn brown when edited, but they also seemed to recruit existing brown cells into action through a chemical messaging system.

“Cells in different tissues communicate with each other,” said  Yu-Hua Tseng, Ph.D., a Senior Investigator in JDC’s Section on Integrative Physiology and Metabolism. “In this case, we found that our transplanted HUMBLE cells secrete a molecule called nitric oxide, which is carried by red blood cells to the endogenous brown cells and activates those cells.”

Science Fiction to Science Fact

More research is required before the technique is rolled out in human trials. Still, if the researchers are successful, their work could lead to a biopharmaceutical approach whereby a patient’s own cells are removed, edited, and reinjected. Failing that, they may be able to surround the edited fat cells in materials that would prevent a patient’s immune system from rejecting the drug. Another option would be the development of a new gene therapy that directly turns on the UCP1 gene.

“Employing cell-based or gene therapies to treat obesity or type 2 diabetes used to be science fiction,” said Tseng. “Now scientific advances, such as CRISPR gene-editing technologies, will help us to improve the metabolism, the body weight, the quality of life, and the overall health of people with obesity and diabetes.”

The team’s work has been published in the peer-reviewed journal, Science Translational Medicine.