Feats of fat burning by ground squirrels inspire research into how this ability could be harnessed to help people with obesity.
March 31, 2014
Every winter, in burrows deep beneath the snow, hibernating rodents perform biological feats that humans can only dream of.
When the rodents periodically rouse themselves during hibernation, they turn fat into heat with astounding efficiency, raising their body temperature by 60 degrees F in just two hours. Their heat engine is deposits of "brown fat," which constitute less than five percent of their total fat tissue. The rest is "white fat," the storage depot common to mammals, including humans.
At the University of Minnesota Duluth, researchers studying 13-lined ground squirrels have found more than 2,000 genes whose activity patterns are related to hibernation. All have counterparts in the human genome.
"All mammals have pretty much the same genes," says Matt Andrews, a McKnight Presidential Professor of biology at UMD. "But [our ancestors] lost the ability to hibernate a long time ago."
While human babies are born with a fair supply of brown fat, most disappears by adulthood. We don't need it for hibernation, but mimicking its fat-burning ability has appeal for obesity control. Someday, Andrews says, the knowledge he and his colleagues are discovering may lead to that.
Similar genes, dissimilar traits
The difference in human and squirrel hibernation abilities rests on differences in which genes are active when. If the hibernation-linked genes were musical instruments, they would form two nearly identical, 2,000-piece orchestras that play different repertoires in our two species. The task of sorting out these patterns falls largely to Marshall Hampton, an associate professor of mathematics at UMD.
Hampton identified hibernation-linked genes in the squirrels' brown fat by sequencing the strands of RNA that active genes produce. Some genes became active during the intermittent awakenings, and others at either the October start or the April end of hibernation. This study laid a basis for understanding how the squirrels, but not humans, can hibernate.
The secret of brown fat
Even after years studying the squirrels, Andrews stands in awe of their ability to withstand the stress of hibernation.
"Their body temperatures get down into the high 30s F. Their heart rate drops from 300-400 beats per minutes down to 5-10, and their oxygen consumption is only two percent of normal," he says.
But during their periodic awakenings, that all changes radically, thanks to brown fat's special fat-burning ability. Here’s the secret:
Animal cells contain tiny factories called mitochondria, which bundle most of the energy from food into a small molecule called ATP, which they produce in large quantities. As ATP is made, a little energy is lost as heat. ATP—the “energy currency” of cells—then supplies energy for virtually all work a cell performs.
During a hibernating squirrel’s periodic awakenings, fat from its white fat reserves is transported to brown fat tissue, which is extraordinarily rich in mitochondria. But when these mitochondria burn fat, they release most of the energy as heat—not ATP.
"It's a tremendous amount of energy—like a person running a half marathon," says Hampton. Says Andrews: "Brown [fat] tissue in hibernators is the world champion fat burner."
Quest for control switches
One of the key steps in the human quest for better fat burning is finding the signals that trigger hibernators’ periodic awakenings. The UMD researchers have been chasing the answer by looking at brain activity during hibernation.
"Brown fat is turned on by nerves," says Hampton. "Ultimately, the central nervous system is making that call. We've looked at activity in ... the hypothalamus of the brain. Somewhere in the hypothalamus is where that decision is made."
As the mysteries of hibernation yield to research, Hampton and Andrews are cautiously optimistic.
"If we can find these little tricks animals use to burn fat, we might be able to mimic them and find a way to stimulate that process," says Andrews.
"But," says Hampton, "we have a lot of interlocking mechanisms to keep our weight the same, and if you push one piece of the system, other pieces fight back. I don't think there will be one compound that will make you lose weight."
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