Why do not the muscles of immobile animals without food weaken in hibernation?

Ground squirrels eat a lot at the end of summer to prepare for hibernation. They need to store a lot of energy as fat. During the winter, this fat will be the main fuel source for squirrels in their hibernation nests underground.

During hibernation, ground squirrels enter a state called sluggishness (torpor). Their metabolism drops by as much as one percent in the summer, and their body temperature can approach freezing.

Slowness greatly reduces the amount of energy the animal needs to survive until spring. Of course, this long-term fast has a downside: there is no new input protein. Protein is vital for the preservation of tissues and organs, and not getting protein is especially problematic for muscles.

In humans, long periods of inactivity, such as prolonged bed rest, lead to muscle wasting. But muscle breakdown in animals in hibernation is minimal. In these animals, despite 6 to 9 months of inactivity and lack of protein intake, muscle mass and function are well maintained. This helpful adaptation will help ensure a successful breeding season in the coming spring.

But where does this ability of hibernating animals come from? For decades, this has been a mystery to biologists studying hibernation. Recently, researchers investigated the role of intestinal microbes in these animals in helping maintain muscle during hibernation.

Ground squirrel in winter sleep

The leopard ground squirrel shows the least signs of muscle wasting even after 6 months of hibernation.

Nitrogen recycling system

Past research has shown that the digestive system of hibernating animals undergoes significant changes in structure and function. Of course, these are not the only animals that fast all winter, their intestinal microbes do the same.

Researchers in a new study have found that winter fasting alters the gut microbiome significantly. They then questioned whether intestinal microbes could play a functional role in hibernation. Do some bacteria help maintain muscle and other tissue function when animals are not eating?

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Biologists have previously identified clever tricks in ruminants such as cattle that help them survive when dietary protein is low or protein requirements are high (such as during pregnancy).

A process called “urea nitrogen recycling” allows the animal to recycle nitrogen (a vital element for making protein), otherwise urea is excreted in the urine. Through this process, urea nitrogen is stored in the body and used to make amino acids, the building blocks of proteins.

The process of urea nitrogen recycling depends on the chemical decomposition of urea molecules to release nitrogen. But the important point is that the chemical decomposition of urea requires “urease” and urease is an enzyme that is not produced by animals. So, for example, how does a cow get that nitrogen from urea?

Certain microbes that are normal inhabitants of the animal gut can do this. They make the enzyme urease, which they use to chemically break down urea molecules and release nitrogen, which becomes part of the ammonia molecule. The microbes then absorb ammonia and use it to make new proteins for themselves.

Urea molecule

A model of the urea molecule, with two nitrogen atoms (blue) along with one carbon atom (gray), one oxygen atom (red) and four hydrogen atoms (white)

Gastrointestinal characteristics of ruminants allow these animals to recover urea nitrogen. But for other animals, such as hibernating animals, it was not clear whether urea nitrogen could help the body make protein. The challenge for scientists was to demonstrate urea nitrogen recycling in hibernating animals.

Experimental design

Using leopard-like ground squirrels, the researchers designed experiments to examine key steps in urea nitrogen recycling. They first injected urea molecules into the squirrels’ blood. In these molecules, two nitrogen atoms were replaced by a heavier form of nitrogen, which is naturally present in small amounts in the body.

They were able to inject heavier nitrogen atoms as urea injected from the blood into the gut, then when microbial urease breaks down the urea into its components, they eventually trace the atoms into metabolites and proteins in squirrel tissue. Wherever higher levels of the heavier form of nitrogen were found, researchers knew that urea was the source of nitrogen, so gut microbes must be responsible for returning urea nitrogen to the animal body.

To confirm that the microbes were doing nitrogen recycling, the researchers compared squirrels with natural microbiomes to squirrels that did not. They put some animals on antibiotics three times a year to kill the gut germs: summer, early winter (when they were hibernating for a month) and late winter (when they were hibernating for four months).

In squirrels with natural microbiome, evidence of nitrogen recycling was observed at each stage of the process tested. But microbiome-free squirrels showed minimal urea nitrogen recycling. The observations confirmed that this process depends on the ability of intestinal microbes to break down urea and release nitrogen in the intestines of hibernating animals. Muscle and liver tissue of hibernating animals Late in winter, most of the urea nitrogen is stored, which means they have been hibernating for a longer period of time without food.

Ground squirrels also participate in this coexistence. During hibernation, their gut cells increase the production of proteins called urea carriers. These molecules are located in the cell membranes of the gut and carry urea from the blood to the gut, where the urea-containing microbes are present. This cooperation means that the small amount of urea that the animal produces during hibernation makes it easier to get to the intestines.

Eventually, the researchers realized that it was not just squirrels that benefited from this process. Microbes also used urea nitrogen to make their proteins. This suggests that urea nitrogen recycling during winter malnutrition provides the important molecular building blocks needed by both parties. The researchers reported the results of their study in the journal Science.

As seen in this video, every few weeks, hibernating squirrels temporarily wake up. They do not eat or leave their nests, but their short-term rise in body temperature allows the enzyme urease to perform its functions.

Can this kind of coexistence help human beings?

This example of the coexistence of hibernating animals and microbes has potential clinical applications. For example, malnutrition, which affects millions of people around the world, causes a gradual decrease in muscle mass and endangers health.

Sarcopenia, or muscle wasting, which is a natural part of aging, impairs mobility and makes people more prone to injury. Understanding how an hibernating animal’s nitrogen recycling system is most effective when the risk of tissue loss and muscle wasting is greatest can lead to new therapies to help people in similar conditions. .

Another potential application in human spaceflight is during which crews experience high rates of muscle atrophy. The cause of muscle atrophy in astronauts is that its microgranulation suppresses muscle protein production. Even the extensive exercise regimen that astronauts do is not enough to compensate. A microbiome-based interaction that facilitates muscle protein production, similar to the process we see in animals hibernating, may be worth considering.

Although these applications are theoretically possible, they are far from practical; But studies in the 1990s showed that humans could recycle small amounts of urea nitrogen with the help of gut microbes, so the machinery needed was there and just needed to be optimized.

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