Spotlight on Research 2013

September 2013

Muscle Stem Cells Can Be Turned Into Energy-Burning Brown Fat Cells in Mice

Adult muscle stem cells in mice can be turned into brown fat—an energy-burning type of fat—by altering the presence of one gene regulator, according to research funded in part by the NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases, and published in the journal Cell Metabolism. The finding could have implications for treating obesity and the health risks associated with it, such as arthritis, type 2 diabetes, insulin resistance, and other disorders.

In contrast to white fat cells that store excess energy, brown fat cells are considered “good fat” because they burn energy and keep body temperature regulated. People with a lower body mass index (BMI) tend to have more brown fat cells than people with higher BMIs. Scientists have been looking for ways to unlock the potential of brown fat in the effort to help people lose weight.

To better understand how brown fat cells are generated, Michael Rudnicki, Ph.D., of Ottawa Hospital Research Institute and the University of Ottawa, and colleagues, focused on adult skeletal muscle stem cells, also called satellite cells. These particular stem cells are derived from the same embryonic tissue as brown fat cells. They typically are activated after muscle training or injury, and work to repair damage. Scientists have long assumed that adult muscle satellite cells were dedicated to giving rise to muscular tissue. Studies had suggested that they were incapable of generating white fat, so it was unclear if they had the potential to become brown fat. “Although we previously found that embryonic muscle stem cells could give rise to brown fat, we were interested in determining whether adult muscle stem cells could also become brown fat,” said Rudnicki.

Earlier research had found that the gene regulator known as microRNA-133 (miR133) may be important in determining how cells differentiate and multiply. Rudnicki was surprised to find that miR133 might also play a role in determining what type of cell satellite cells ultimately become. To determine if they could prompt satellite cells into becoming brown fat cells, Rudnicki and colleagues injected adult mice with an antisense oligonucleotide (ASO), an agent engineered to bind with miR133 and inhibit it from functioning. In the ASO-treated mice, more of the satellite cells became brown fat cells compared to untreated mice. The treated mice also were more resistant to diet-induced obesity and were better able to process sugar. In addition, these mice burned more calories than their untreated counterparts four months after treatment. Further experiments with normal mice found that miR133 levels were reduced in mice exposed to cold temperatures, resulting in increased brown fat cell development.

"We found that miR-133 functions as a switch that regulates the future identity of the satellite cell. By learning how to manipulate it, we have identified one potential therapeutic target for treating obesity and the health conditions that frequently accompany it," Dr. Rudnicki concluded.

This research was also supported by the Canadian Institutes of Health Research, Ontario Research Fund, and the European Commission 6th Framework.

Colleen Labbe, M.S.

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Yin H, Pasut A, Soleimani VD, Bentzinger CF, Atoun G, Thorn S, Seale P, Fernando P, van Ijcken W, Grosveld F, Dekemp RA, Boushel R, Harper ME, Rudnicki MA. MicroRNA-133 controls brown adipose determination in skeletal muscle satellite cells by targeting Prdm16. Cell Metab. 2013 Feb 5;17(2):doi: 10.1016/j.cmet.2013.01.004. PMID: 23395168

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