What if the best way to conquer obesity is to have fat injected into your stomach?
According to two studies in Nature, that may be the future of weight loss treatments—provided you use the right kind of fat.
When we think of the stuff, we usually call to mind white fat, which stores calories and migrates to our waistlines. But fat isn't all bad. So-called brown fat releases the energy it captures and promotes calorie burning—and thus weight loss.
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The two Nature studies describe two different proteins that control the creation of brown fat cells from immature muscle and fat cells in mice. The findings offer new hope in the fight against obesity—a condition, which, according to the U.S. Centers for Disease Control and Prevention, grips two thirds of American adults and 17 percent of young people aged 19 and under.
Conceivably, drugs that make more of these proteins could jump-start a conversion of white fat cells to brown fat cells. Alternatively, according to Bruce Spiegelman, co-author of one of the new studies and a biologist at Boston's Dana–Farber Cancer Institute, brown fat cells could one day be transplanted into an obese person's abdomen—where their white fat stores live—to fuel the calorie-burning processes.
"The white fat is the main energy storage in our body," says Yu-Hua Tseng, a biologist at Joslin Diabetes Center at Harvard University and co-author of the other Nature study. "The white cells can release free fatty acids, and they are moved over to the brown fat to be burned," resulting in weight loss.
In humans, most brown fat disappears shortly after birth—when it has fulfilled its role of keeping a newborn's body temperature stable. In mice, however, it persists until adulthood, primarily between the shoulder blades, where it performs the same internal climate-control function. According to Tseng, even though mature brown fat cells are few and far between in the human body, immature cells that could grow into them (so-called progenitors) are available.
Tseng's group used a growth protein that in previous work by her lab was also shown to drive the production of brown fat cells by turning on a fleet of genes that promote the development of brown fat.
When she and her team introduced the protein into mice—by attaching it to a disabled common cold virus and letting the pathogen infect the animal's cells—it caused the formation of more brown fat and led to mice that were leaner than those that didn't receive the protein. In addition, Tseng's group showed that immature fat cells transfused into mice produce scores of the protein, and that the cells developed into brown fat, rather than white.
Spiegelman's study found a close relationship between brown fat and muscle by identifying a protein that determines whether a young cell will grow into a one or the other. When the levels of this biological switch are elevated in cells, the cells mature into brown fat; when it is lower than normal, these cells become muscle.
From his own previous work, however, he has shown that high levels of the protein also reprogram white fat cells into brown ones. "We and everyone else thought this was some sort of choice in the [fat] lineage," he says. "It was surprising that brown fat is part of the muscle lineage."
Both groups are moving forward with their target proteins to determine whether they are able to induce the formation of brown fat in obese mice, stimulate calorie burning, and cause no other adverse metabolic effects. "As we think about strategies to treat obesity and elevate [protein levels], we want to know the other forms of biology that it might be involved in," says Spiegelman.
Philipp Scherer, a biologist at the University of Texas Southwestern Medical Center at Dallas, says that the two studies offer local solutions for combating obesity, rather than tweaking a protein in the brain that is involved in energy use or food intake—but could also affect mood and mental health. "As long as we can just play with the fat out there," he explains, "we are on much safer ground."
Tseng says that although it is her and Spiegelman's shared goal to develop a treatment for obesity—she intends any therapies for a segment of the population that is genetically predisposed to be overweight. "The best approach for weight reduction for the general population is still a good diet and exercise," she notes.
