Not so nutty: Fat-burning squirrels may hold clues for future diet drugs

The gophers in Matt Andrews' lab don't seem to be doing anything scientific. They're asleep, curled up on sawdust beds inside clear plastic shoebox-size bins.

Inside those tiny bodies, though, there's a lot going on. They store a special kind of brown fat that's also found in humans. It burns like crazy and energizes the creatures when they awake during hibernation every 10 days or so.

"Just like you would start a fire out in the woods if you wanted to warm up, what they do is they burn their fat. But they burn that fat so efficiently, they burn that fat so well, it really is nature's fat-burning machine," says Andrews, a University of Minnesota-Duluth biologist. "We know of no other example in the natural world where fat can be melted away that quickly."

Unlocking the secrets to "nature's fat-burning machine" could be a big deal in a nation that spends billions each year on weight loss. While a gopher diet pill is a long way away, Andrews and other UMD scientists have identified thousands of genes in the fat of these creatures that could someday lead to drugs that help burn fat in humans.

Andrews has been studying gophers, which are really 13-lined ground squirrels, and their hibernation for years. When the ground squirrel crawls into its burrow every October, its body goes through changes that would quickly kill humans, including a heart rate that drops from more than 300 beats per minute, to fewer than 10. Their body heat increases rapidly as they awaken.

"The oxygen consumption in these animals is about 2 percent of normal. Yet they don't get a stroke, they don't have a heart attack, they're perfectly protected from these things," Andrews said during a recent visit to his lab. "How can they survive such profound hypothermia, these body temps that go down almost right down to freezing?"

In his lab, Andrews mimics the animals' winter sleep conditions in a "hibernation chamber." His research helped develop a therapy that extends the length of time someone can survive after suffering severe blood loss.

When he and UMD mathematician Marshall Hampton began examining the genetics of the squirrels' brown fat, known as brown adipose tissue, he discovered certain fat genes are turned on when the squirrel wakes up.

As they looked closer at the gene sequences, Andrews and Hampton discovered that almost every one of them was also in the human genome.

"We have these genes. It's just that the hibernator, in its brown adipose tissue, can selectively turn them on, turn them off, which allows them to efficiently burn fat, and that's something through evolution we've lost the ability to do," Andrews said.

Babies are born with a small amount of brown adipose tissue. It was long thought that adults gradually lost their brown fat. But about five years ago scientists found that adult humans also have the tissue, near our shoulder blades.

And the more brown fat people have, the thinner they are.

The pharmaceutical industry has tremendous interest in discovering how those genes turn on and off, said Steve Kliewer, an expert on brown fat at the University of Texas.

That knowledge could someday lead to a new kind of diet pill, he added, though "biology is always complex, and there are always mechanisms that push back."

Any treatment, for instance, would have to be coupled with moderate eating to compensate for turning on the brown adipose tissue, he said, adding that there are years of work ahead.

Hibernators are also yielding important breakthroughs in other areas.

For example, if humans were to sleep for six months, our muscles would be severely atrophied when we woke up. But not ground squirrels, said Ronnie Cohn, chief of genetics at the Hospital for Sick Children in Toronto.

"They start hibernating, they don't move, they don't drink, they don't eat, and they don't lose any muscle mass," said Cohn, who hopes his work could lead to a drug to help people, for example, suffering from muscular dystrophy.

In his lab, Andrews carefully cups one of the snoozing squirrels in his hands. "It curls up in a tight little ball, and that's how it spends the winter for periods of about 1 to 2 weeks," he says. "We just have to find the right plant or animal to look at," he adds, "to get ideas to solve problems that nature has solved already."

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