healthmedicinet

In what obesity experts are calling a potentially groundbreaking discovery, Ottawa scientists have found a way — at least in mice — to trigger the body to produce more calorie-burning brown fat, a feat that may open the door to new treatments for obesity using good fat to fight bad fat.

Their study is the first to show that stem cells destined to become muscle cells can be transformed into brown fat, a heat-generating tissue that burns off stored calories.

When mice were injected with a compound in their hind legs that promotes the creation of brown fat from muscle stem cells, the treated rodents produced more brown fat and were noticeably leaner, four months later.

Despite the promise, crucial questions remain and any potential treatment in humans is years away, the researchers caution.

However, “We were really surprised that, months after the intervention — and we looked as long as four months after — that these mice were slimmer than the control mice, and were continuing to get slimmer,” said Dr. Michael Rudnicki, a senior scientist and director of the regenerative medicine program at the Ottawa Hospital Research Institute.

In addition, the injected hind leg was hotter compared to the untreated muscle, meaning the metabolic rate of the mice was higher and there was increased energy production throughout the entire body.

“By a whole battery of tests we show that these animals are metabolically doing better. They’re slimmer, and have better glucose control,” said Rudnicki, a Canada Research Chair at the University of Ottawa.

“They just didn’t gain weight at the same degree,” he said. “Rather than storing fat, they’re burning it.”

Currently, about 62 per cent of the Canadian adult population is overweight or obese, and the heaviest weight classes are growing the fastest.

The body contains two types of fat: white fat and brown fat. Brown fat is abundant in newborns; it helps keep their body temperature warm. “But, by the time we’re two, all the brown fat is pretty well gone,” says Dr. David Lau, a professor of medicine at the University of Calgary. Brown fat is scarce in most adult humans, and women tend to have even less of it than men. Most of it located in small amounts above the large blood vessels of the neck, around the collarbone.

Brown fat contains massive amounts of mitochondria, tiny energy sources or miniature furnaces. It burns calories in the form of heat.

Stem cells are the “master” cells that provide the starting material for every organ and tissue in the body. Stem cells have the ability to differentiate, or develop into highly specialized cells, such as heart, bone and muscle cells.

In 2007, Rudnicki’s team was the first to identify the existence of muscle stem cells in adults.

Now they’re the first to show how these same stem cells can be turned into brown adipose tissue — brown fat.

The key is a gene regulator or genetic switch that, when present, turns stem cells into muscle. When there’s less of it, the stem cells become brown fat.

Rudnicki’s group used a special compound, called an antisense oligonucleotide, or ASO, to “antagonize” or reduce the amount of that gene regulator in mice.

The work involved ordinary lab mice fed a high-fat diet. “They’re in a cage, they don’t have a wheel to run on, and so, as they age, they get overweight,” Rudnicki said. “Some of the strains become very overweight.”

The team tested to see whether they could manipulate a muscle stem cell to turn into brown fat by injecting the ASO directly into a single leg muscle.

Other ASOs that target different genes are already being tested in humans for the treatment of heart disease, cancer and other illnesses. It’s conceivable, Rudnicki says, ” that a similar strategy could be used using this so-called ASO to treat obesity in humans.”

Still, the work is in its early days. The team hasn’t shown that the treatment makes fat mice skinny, though it does appear to keep mice predisposed to obesity from becoming obese. It’s also not clear how long the effects would last, and whether there would be any side effects.

“The whole safety thing has to be worked out,” Rudnicki said. “(But) it’s the biology that’s really cool.

“We’ve found a genetic switch that controls what these cells are going to be when they grow up, and we can move them from one to the other.”

The Ottawa team’s work is published this week in the journal Cell Metabolism.

Lau, of the University of Calgary, says the study “basically tells us that you can manipulate the body into transforming the stem cells that are destined to form skeletal muscle to become brown fat.”

While it’s a “huge stretch” at this point to say it could potentially be a treatment for obesity, “it’s an exciting piece of basic science research,” Lau said.

Dr. Arya Sharma, scientific director of the Canadian Obesity Network, says the finding “improves our understanding about the biology of brown fat, and brown fat is a tissue that is of great interest when it comes to obesity.”