Scientists at the University of Utah are looking at how bears and other mammals hibernate in an effort to find genetic clues for combating human obesity and related diseases. By finding the right genetic switches, it may be possible to learn why some animals don't suffer from morbid obesity and resist related diseases.
Hibernation is a remarkable adaptation by many species of mammals. By gorging on food in the late summer and autumn, these animals are able to build a store of fat large enough to allow them to retire into their dens and comfortably spend the bitter cold of winter sleeping or in a state of torpor.
It's a process that is of great interest to scientists – not only as an intriguing puzzle in and of itself, but also for its potential in medicine or as a way for astronauts to sleep through most of a long interplanetary mission.
Another point of interest is the fact hibernating animals seem to be resistant to all sorts of conditions. In the run-up to winter, they gorge on enormous amounts of food and put on so many pounds that it would make a human of comparable size morbidly obese. But despite this, bears and other hibernators are resistant to heart disease, cancer, and diabetes, as well as being able to remain dormant for months without losing bone or muscle mass. Scientists want to find out why and are seeking the answer in DNA.
"Hibernators have evolved an incredible ability to control their metabolism," says Christopher Gregg, Ph.D., associate professor in the Department of Neurology & Anatomy. "Metabolism shapes risks for a lot of different diseases, including obesity, type 2 diabetes, cancer, and Alzheimer's disease. We believe that understanding the parts of the genome that are linked to hibernation will help us learn to control risks for some these major diseases. A big surprise from our new study is that these important parts of the genome were hidden from us in 98 percent of the genome that does not contain genes – we used to call it 'junk DNA'."
Working with bioinformatician Elliot Ferris, Gregg looked for genetic switches or regulatory elements that give animals these abilities in hopes that similar regions in the human genome can be identified – especially those that are related to obesity.
The team looked at four hibernating mammals – the thirteen-lined ground squirrel, little brown bat, gray mouse lemur, and lesser Madagascar hedgehog tenrec. Comparing their genomes, they found that each one had independently evolved short, non-coding DNA snippets known as parallel accelerated regions, and that there are similar regions that are found near genes related to human obesity more often than would be expected.
They found a particular link to genes involved in Prader-Willi Syndrome (PWS), which causes an insatiable appetite leading to morbid obesity. These genes have more hibernator accelerated regions compared to those not associated with the genetic disorder.
Hibernating animals develop a similar insatiable appetite, called hyperphagia, but they may have evolved the means to genetically turn this on and off, which could help researchers to better understand human obesity and control it. So far, the team has identified 364 potential genetic elements that might be related to hibernation and obesity and are currently testing these on mice using CRISPR epigenome editing technology.
"Our results show that hibernator accelerated regions are enriched near genes linked to obesity in studies of hundreds of thousands of people, as well as near genes linked to a syndromic form of obesity," says Ferris. "Therefore, by bringing together data from humans and hibernating animals, we were able to uncover candidate master regulatory switches in the genome for controlling mammalian obesity."
The research was published in Cell Reports.
Source: University of Utah
