If you’ve tried to lose weight, you may have wished for a pill that would help you burn calories with little or no exercise. Because such a drug could treat obesity, which affects over one-third of Americans, many researchers are working toward this goal. Treatments that boost calorie burning could enhance the limited efficacy of current weight-loss drugs that suppress appetite.

Most scientists in this field focus on brown adipose tissue, a type of fat that’s specialized to convert calories to heat to keep you warm in the cold. The challenge with that approach is that most adults have very little brown fat—therapies would have to first convert regular white fat to brown. Instead, the laboratory of Muthu Periasamy, PhD, professor in the Center for Metabolic Origins of Disease, is investigating how to stimulate another, more plentiful tissue—muscle—to do the same thing.

Periasamy and Naresh Bal, PhD, a staff scientist in his lab, got the idea that muscle could be important for generating heat from birds—they don’t have any brown fat, but they can still keep themselves warm without constant shivering. In a paper recently published in the Journal of Biological Chemistry, Bal removed the brown fat from mice to examine whether muscle can effectively generate heat in mammals.

“Not only did these mice maintain near-normal body temperatures when living in the cold,” said Bal, “but they burned more calories than mice whose brown fat remained intact—they lost three times as much fat after nine days at cold temperatures.” The extended exposure is required to eliminate the contribution of shivering, which stops after they become adapted to the cold, within the first few days.

“These results suggest that inducing muscle to generate heat could be an even more efficient way to treat obesity than doing the same in brown fat,” said Periasamy. “This is the first step toward drugs that activate this process, called nonshivering thermogenesis (NST).”

“Our next step is to determine which factors turn on NST in muscle,” added Bal.

The lab’s work so far has provided some clues. They have previously shown that the protein sarcolipin changes the way muscle cells use ATP, causing them to generate heat instead of contract. In this research, they observed much higher levels of sarcolipin in the muscles of cold-adapted mice who lack brown fat.

“Since sarcolipin acts by binding another protein, it probably wouldn’t be easy to block,” explains Bal. “To find better drug targets we plan to look at how it affects its target protein, a calcium pump, and how that changes calcium dynamics. Ultimately, we might be able to mimic those effects with a drug.”

The paper is available online here.