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Insights into Energy-Burning Fat Cells

Beige fat (top), and brown fat (bottom). The darker color is due to the presence of energy-generating mitochondria.Image courtesy of the researchers

Humans have 2 main types of fat: white and brown. White fat, which tends to be located under the skin and around internal organs, stores excess calories. Too much white fat, a characteristic of obesity, increases the risk of several metabolic disorders.

Brown fat, in contrast, burns energy to create heat and help maintain body temperature. Brown fat is present in mammals, including mice and human infants. It’s activated by cold temperatures and other triggers.

Researchers have identified a specific type of fat cell, known as beige, that has some characteristics of brown fat. Beige fat cells appear in white fat in response to specific triggers such as cold. It’s unclear whether they arise from conversion of white fat cells into a more brown-like state, production of new beige cells, or a combination of both. Beige fat cells are also referred to as brite cells, for brown in white.

Since beige and brown fat cells are able to burn calories, they could potentially serve as targets for therapies to try to reduce obesity and its associated disorders. Brown fat, however, can be difficult to find in adult humans, and its origin isn’t clear.

A team of researchers led by Dr. Shingo Kajimura at the University of California, San Francisco, set out to determine the nature of brown and beige fat from adult humans, and to better characterize it at a cellular level. The study was funded in part by NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Institute of General Medical Sciences (NIGMS). Results were published in the April 2015 issue of Nature Medicine.

The group obtained cells from biopsies from the shoulder area of 2 normal weight adults and grew them in culture dishes. They then identified specific populations of cells with a protein marker of brown fat cells known as uncoupling protein 1 (UCP1).

The scientists surveyed genes that were active in the human fat cells and found that they were similar to those active in mouse beige fat cells, but not in mouse brown fat cells. Novel genes whose expression marked human beige cells included potassium channel K3 (KCNK3) and mitochondrial tumor suppressor 1 (MTUS1). Analysis of these 2 genes in mice revealed that they were required for beige fat cells to become brown fat cells and to burn energy to create heat.

“This finding brings us another step closer to the goal of our laboratory, which is engineering fat cells to fight obesity,” Kajimura says. “We are trying to learn how to convert white fat into brown fat, and until now, it had not been demonstrated that this recruitable form of brown fat is actually present in humans.”

The group plans to use the beige fat cells to screen different molecules to determine how to stimulate the heat-producing activity of human brown fat.

— by Carol Torgan, Ph.D.