‘Hibernation genes’ help control metabolism and feeding — and could hold untapped benefit for humans
Hibernation mammals rely on particular genes to adjust their metabolisms when they enter this unique and low energy state – and humans actually carry the same DNA linked to hibernation.
Now the first research suggests that the exploitation of this particular DNA could help treat medical conditions in people, according to scientists.
Hibernation offers “a whole bunch of biometricly important superpowers” Christopher GreggA professor of human genetics at the University of Utah, told Live Science.
For example, terrestrial squirrels can develop reversible Insulin resistance This helps them quickly gain weight before hibernating but begins to disappear as Hibernation begins. A better understanding of how the hibernators Flippts This switch could be useful to tackle insulin resistance that characterizes Type 2 diabetesSuggested Gregg.
Hibernation animals also protect their nervous system from damage that could be caused by sudden changes in blood circulation. “When they come out of hibernation, their brain is reperfused,” said Gregg. “Often it caused a lot of damage, like a strokeBut they have developed ways to prevent these damage from occurring. “”
Gregg and his colleagues think that drawing it from hibernation genes from people could unlock similar advantages.
In relation: The best card of the human genome highlights the “jump genes”, “unwanted DNA” and more
A “hub” of hibernation genes
In a pair of studies published Thursday, July 31, in the journal Science, Gregg and his team identified key levers which control the genes linked to hibernation, showing how they differ between animals that hibernate And those who don’t. Then, in laboratory experiences, they plunged into the effects of Deletion of these levers in laboratory mice.
Although mice don’t do it hibernateThey can enter into torpor – a lethargic state of metabolism, movement and body temperature which generally lasts less than a day – after fasting for at least six hours. This made mice an appropriate genetic model to study these effects.
Use of gene editing technique CrisprScientists have designed mice with one of the five non -coding CIS elements kept deactivated or “eliminated”. These cres act as levers to control the genes which, in turn, code for proteins which fulfill biological functions.
The targeted cres in the study are near a group of genes called “fatty locus and linked to obesity” or the Locus FTO, which is also in humans. The variants of genes found in the cluster have been linked to a high risk of obesity and related conditions. In general, Locus FTO is known to be important to control metabolism, energy expenditure and body mass.
By eliminating the CRES, the researchers were able to modify the weights, the metabolic rates and the behaviors of research of the mouse. Some deletions accelerated or slowed weight gain, others have increased or lowered the metabolic rate, and some have affected speed statement.
This observation is “very promising”, in particular since the Locus FTO plays a well -known role in human obesity, Kelly drewA specialist in the biology of hibernation at the University of Alaska Fairbanks, told Live Science in an email.
Taking a CRE – called E1 – In female mice led them to gain more weight on a diet rich in fats than a comparison group with all their intact DNA. The removal of a different CRE, called E3, changed the search for food for male and feminine mice, specifically changing the way they were looking for hidden foods in an arena.
“This suggests that significant differences in food and decision processes may exist between hibernateurs and non-hibners and the elements we have discovered could be involved,” Gregg said.
Unknown to approach
The authors of the study said that their results could be relevant to humans, because the underlying genes do not differ much from the other. “It’s like that [the mammals] Light and deactivate these genes at different times, then for different durations and in different combinations that shape different species, “said Gregg.
However, “it is certainly not as simple as to introduce the same changes in human DNA”. Joanna KelleyA professor specializing in functional genomics at the University of California in Santa Cruz, told Live Science in an email. “Humans are not capable of torpor induced by fasting, which is the reason why mice are used in these studies,” said Kelley, who was not involved in the work.
She suggested that future work include animals incapable of torpor and focus on unpacking all the downstream effects of the deleted CRES. In the current state, this study “definitively underlines the field in a new direction” in terms of knowing how scientists include genetic controls stimulating changes in hibernateurs throughout the year, she added.
Drew also pointed out that torpor in mice is triggered by fasting, while real hibernation is triggered by hormonal and seasonal changes and internal clocks. Thus, although the CRES and the genes identified by the study are probably critical parts of a metabolic “toolbox” that responds to fasting, they may not be a “main switch” that lights or deactivate hibernation.
“Nevertheless, discovering these fundamental mechanisms in a towable model like mice is an invaluable springboard for future research,” said Drew.
Gregg has stressed that many things remain unknown, especially why the effects of certain deletions differ in female mice compared to male mice or how changes in food behavior observed in mice could manifest itself in humans. The team also plans to search for what would happen if they deleted more than one CRE linked to hibernation both at the mouse.
On the line, Gregg thinks that it may be possible to modify the activity of the “Hub Hub Hub” of humans with drugs. The idea would be that this approach could give the advantages of this gene activity – such as neuroprotection – without patients having to hibernate, he said.
