Origins of calorie-sizzling fat cells uncovered in mice.
To most dieters, no fat is good fat. But in work published this week in Nature, an insight into the origin of a special class of calorie-burning fat cells could lead to new ways of boosting metabolism and combating obesity, researchers say.
The sworn enemy of the dieter is the 'white' fat cell. Such cells are little more than sacks of fat, storing energy and providing padding. Less known — and less reviled — is brown fat, made up of heat-producing cells chock full of fat and energy-generating structures called mitochondria. The iron attached to proteins in these mitochondria gives brown fat its characteristic colour.
White fat is by far the more abundant of the two; adults carry many pounds of white fat, but only a few grams of brown fat, concentrated mainly in the front part of the neck and the upper chest. Brown-fat pads between the shoulder blades are thought to help newborns stay warm, but precisely what purpose the cells serve in adults is still unclear.
What is clear is that brown fat burns a tremendous amount of energy: about 50 grams of brown fat could burn up 20% of a person's daily caloric intake, says Ronald Kahn of the Joslin Diabetes Center at Harvard Medical School in Boston, Massachusetts, and one of the researchers involved in the latest study.
"It's a very efficient tissue at wasting energy," agrees Bruce Spiegelman of the Dana-Farber Cancer Institute and Harvard Medical School, another member of the team. "It's basically a fire that's just burning."
That would seem to prompt a simple solution to the growing obesity problem: find a way to generate a extra brown fat and let the body burn away the energy stored in its excess white fat.
Fuel for the fire
That notion surfaced last year when a team of researchers led by Spiegelman found that a protein called PRDM16 could trigger cells that usually produce white fat cells to make brown fat cells instead (see Metabolic switch delivers healthy fat).
Now, two papers in Nature extend that work. Spiegelman and his colleagues have traced the natural origin of brown fat cells1. They used a fluorescent protein to label a population of cells (called myoblasts) that usually generates muscle, and found that PRDM16 could trigger these cells to form brown, but not white, fat cells. Blocking production of the PRDM16 protein caused these brown fat cells to revert back to muscle. The result runs counter to the previous notion that brown and white fat cells shared similar origins.
Meanwhile, Kahn together with Yu-Hua Tseng and their colleagues have identified another protein, called 'bone morphogenic protein 7' or BMP7, that is crucial to the generation of brown fat cells. When researchers overexpressed the protein, mice developed slightly more brown fat, slightly higher body temperatures and exhibited slightly lower weight gain than untreated mice after just five days2.
Kahn feels that the change in weight gain could be more dramatic over a longer time period. His team is testing — thus far only in mice — a commercially available form of BMP7 that is used to encourage bone healing after some surgeries. Because BMP7 can also stimulate bone formation, it must be used with care, Kahn says. His lab is working out conditions that could encourage accumulation of brown fat without forming bone tissue in undesired locations. "Otherwise you could have rock hard abs but not in the way you'd expected," he says.
The work could open new therapeutic avenues, says Dominique Langin, a clinical biochemist at the National Institute of Health and Medical Research (INSERM) in Toulouse, France. But it will be important, he adds, to characterize the process further in humans. In large mammals such as humans, the brown fat present at birth disappears and then reforms in other locations, and the contribution that brown fat makes to overall metabolism is unclear. In mice, brown fat does not undergo the same shift, and it plays a clear role in regulating body temperature.
Seale, P. et al. Nature 454, 961–967 (2008).
Tseng, Y.-H. et al. Nature 454, 1000–1004 (2008).
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Ledford, H. Boosting 'good' fat to burn off the bad. Nature (2008). https://doi.org/10.1038/news.2008.1051