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How stem cells can fight obesity

Otttawa scientists have discovered a trigger that turns muscle stem cells into brown fat, a form of good fat that could play a critical role in the fight against obesity. Fighting fat with fat? The recent stem cell discovery identified a potential obesity treatment, says research from the Ottawa Hospital Research Institute. The study is a collaboration that included researchers from the Ottawa Hospital Research Institute, University of Ottawa, University of Ottawa Heart Institute, Nordion, Erasmus Medical Centre in the Netherlands and University of Copenhagen.

How stem cells can fight obesity.
Photo credit: Rudnicki et al., Ottawa Hospital Research Institute, published in Cell Metabolism. Fighting fat with fat: Stem cell discovery identifies potential obesity treatment.

The findings from Dr. Michael Rudnicki's lab, based at the Ottawa Hospital Research Institute, were published online ahead of print on February 5, 2013 in the prestigious journal Cell Metabolism. You can check out the abstract of the study, "MicroRNA-133 Controls Brown Adipose Determination in Skeletal Muscle
Satellite Cells by Targeting Prdm16."

"This discovery significantly advances our ability to harness this good fat in the battle against bad fat and all the associated health risks that come with being overweight and obese," says Dr. Rudnicki, according to the February 5, 2013 news release, "Fighting fat with fat: Stem cell discovery identifies potential obesity treatment."

Rudnicki is a senior scientist and director for the Regenerative Medicine Program and Sprott Centre for Stem Cell Research at the Ottawa Hospital Research Institute. He's also a Canada Research Chair in Molecular Genetics and professor in the Faculty of Medicine at the University of Ottawa.

Globally, obesity is the fifth leading risk for death, with an estimated 2.8 million people dying every year from the effects of being overweight or obese, according to the World Health Organization

The Public Health Agency of Canada estimates that 25% of Canadian adults are obese. In 2007, Dr. Rudnicki led a team that was the first to prove the existence of adult skeletal muscle stem cells. In the paper published today, Dr. Rudnicki now shows (again for the first time) that these adult muscle stem cells not only have the ability to produce muscle fibres, but also to become brown fat. Brown fat is an energy-burning tissue that is important to the body's ability to keep warm and regulate temperature. In addition, more brown fat is associated with less obesity.

Perhaps more importantly, the paper identifies how adult muscle stem cells become brown fat. The key is a small gene regulator called microRNA-133, or miR-133. When miR-133 is present, the stem cells turn into muscle fibre; when reduced, the stem cells become brown fat.

The recent study reveals how adult muscle stem cells become brown fat

Dr. Rudnicki's lab showed that adult mice injected with an agent to reduce miR-133, called an antisense oligonucleotide or ASO, produced more brown fat, were protected from obesity and had an improved ability to process glucose. In addition, the local injection into the hind leg muscle led to increased energy production throughout the body—an effect observed after four months.

Using an ASO to treat disease by reducing the levels of specific microRNAs is a method that is already in human clinical trials. However, a potential treatment using miR-133 to combat obesity is still years away.

Will stem cells help obese adults to lose weight?

"While we are very excited by this breakthrough, we acknowledge that it's a first step," says Dr. Rudnicki, according to the news release. "There are still many questions to be answered, such as: Will it help adults who are already obese to lose weight? How should it be administered? How long do the effects last? Are there adverse effects we have not observed yet?"

The article's authors are: Hang Yin, Alessandra Pasut, Vahab D. Soleimani, C. Florian Bentzinger, Ghadi Antoun, Stephanie Thorn, Patrick Seale, Pasan Fernando, Wilfred van IJcken, Frank Grosveld, Robert A. Dekemp, Robert Boushel, Mary-Ellen Harper, and Michael A. Rudnicki. This research was funded by the Canadian Institutes of Health Research, the National Institutes of Health, the Ontario Research Fund and EuTRACC, a European Commission 6th Framework grant.

If you look at the picture that comes with this article, you'll see that in this picture taken with a thermographic camera after four months, the mouse treated with miR-133 ASO (on the right) is noticeably leaner. In addition, the injected hind leg (on the left in the image) is 0.8 C hotter than the control mouse.

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