WASHINGTON – Transforming fat cells into calorie-burning machines may sound like a fantasy — the ultimate form of weight control — but the idea is not as far-fetched as it sounds.
Unexpectedly, some fat cells directly sense dropping temperatures and release their energy as heat, according to a new study, and that ability might be harnessed to treat obesity and diabetes, researchers suggest.
Fat is known to help protect animals from the cold, and not only by acting as insulation. In the early 1990s, scientists studying mice discovered that cold temperatures trigger certain fat cells, called brown adipose tissue, to release stored energy in the form of heat — in other words, to burn calories.
Researchers have always assumed this mechanism was an indirect response to the physiological stress of cold temperatures, explains cell biologist Bruce Spiegelman of Harvard Medical School. The activation of brown fat seems to start with sensory neurons throughout the body informing the brain of a drop in temperature. In response, the brain sends out norepinephrine, the chief chemical messenger of the sympathetic nervous system, which mobilizes the body to cope with many situations. In experiments with animals, stimulating norepinephrine receptors triggered brown adipose tissue to release its energy and generate heat, while animals bred to be missing these receptors were unable to mount the same fat-cell response.
People also have brown adipose tissue that generates heat when the body is cold. And unlike white fat, which builds up around the abdomen and contributes to many disorders including heart disease and diabetes, this brown fat is found in higher proportions in leaner people and seems to actively protect against diabetes.
With brown fat, the heat-generating process depends on a protein called UCP1; the protein is also thought to be central in preventing diabetes. Researchers are exploring ways of activating this molecular pathway. But in trying to figure out exactly how fat cells respond to the body’s being cold, Spiegelman and colleagues made some discoveries about white fat cells.
In a study published last week in the Proceedings of the National Academy of Sciences, the researchers exposed various kinds of fat cells to cold temperatures directly. “We were a little surprised that no one had tried this before,” Spiegelman says.
The researchers cooled several types of lab-grown human fat cells — brown, white and beige (white adipose tissue with some brown cells mixed in) — to temperatures between 27 and 39 degrees for four hours, eight hours or up to 10 days.
White and beige cells responded in dramatic fashion. Their levels of UCP1 doubled within eight hours of the treatment. The change in UCP1 also proved to be reversible: Its level returned to normal once the cells’ temperature was set at 37 degrees. But in brown fat cells, no induction of the protein was observed, indicating that cold temperatures don’t mobilize these cells by flipping this particular switch.
The researchers also found that white fat cells obtained from mice lacking receptors for norepinephrine were still able to respond to cooling by turning on UCP1 — showing that the heat-generating pathway is both specific to those fat cells and independent of the sympathetic nervous system.
The finding won’t lead to an anti-fat pill any time soon, Spiegelman says, but it does give scientists new avenues to explore.
“It’s a piece of the basic science, adding to an evolving awareness that fat cells have many lives that we never knew about. Now we know they can sense temperature directly. The next question is: How do they do it, and can that ability be manipulated?”
“The paper is filling in an emerging picture that adipose tissue can be a more flexible, adaptive organ than we once thought,” said Sven Enerback, a physician and adipose tissue researcher at the University of Gothenburg in Sweden. “The finding raises the question of whether this new pathway has widespread effects on the animal as a whole.”