Readers perennially on the lookout for the next big thing in weight loss have heard of brown fat: those mitochondria-rich fat cells found plentifully between the shoulder blades of mice, babies and young, thin people. The bodies of people and animals with large stores of brown fat rev higher, burn more calories and tend not to become obese.
In recent years, researchers suggested that increasing brown fat stores--or promoting the conversion of white fat to the brown kind--could help prevent or even reverse obesity. Exposure to cold seemed to be one way to brown up white fat, but scientists acknowledged they didn't understand why that happened.
Now, a team of scientists led by a UC San Francisco immunologist has found that the immune system could hold the key to turning white fat, if not brown exactly, at least beige. The immune process they describe appears to be set in motion by cold, and it works on white fat cells that are dispersed around the upper back, the chest and the viscera, above the kidneys. But gaining a better understanding of how that happens may lead to easier or more effective ways of boosting our bodies' fat-burning power than, say, plunging ourselves into cold water on a regular basis.
UC San Francisco's Dr. Ajay Chawla, who conducted much of the early research on cold exposure and brown fat, led a team hoping to peer into the mysterious process by which white fat cells--which tends to beget more of themselves--instead take on more of the dark cellular furnaces and burn more fuel to sustain themselves.
The article was published this week in the journal Cell.
In mice, Chawla's team showed that when white fat was exposed to cold, the immune system sent out the signaling proteins interleukin 4 and interleukin 13, which in turn drew macrophages (immune cells that engulf and digest invading pathogens) into white fat. Inside the white fat cells, macrophages produced an organic compound called catecholamines, which made the white cells beige and ramped up their energy needs.
When the researchers increased the amount of interleukin 4 in mice, they developed more beige fat mass, and lost weight. When they bred mice incapable of producing interleukin 4 or interleukin 13, they found that the mice had less beige fat, burned fewer calories and could not maintain a normal body temperature when exposed to the cold.
The study offers scientists hunting for a diabetes cure a whole new approach--one that targets the immune system rather than the brain or gut, where appetite and satiety signals are produced. And it suggests that the body's energy-consumption rates are not strictly under the control of the brain or endocrine (hormone) system, but can be altered by tweaking the immune system.
Chawla and many other researchers now believe that the potential to exploit brown fat for weight loss is significant.
“If you could increase energy expenditure by even a few percent, over a period of a year or two years you would make a big difference," he said.
At the same time, Chawla cautions that "beiging" fat for weight loss may not work for everyone. Individuals will probably vary in how large their brown fat reserves are and how much "beige" fat they can generate. Women appear to have less brown fat than men, and humans have less as we age.