A rodent that recycles nitrogen for wintering

Thanks to hibernation, groundhogs, hedgehogs and many other animals face winter by slowing down their metabolism by up to 99% during the hypothermic phases. However, these fasting periods lead to significant protein imbalances as they deprive hibernators of essential nutrients. This is the case of nitrogen, a constituent element of amino acids and, therefore, of proteins, usually provided by food and which is especially involved in muscle maintenance. In animals, the degradation of proteins leads to the release of ammonia (NH3), a toxic compound for the body, which the liver cells transform into urea. The latter therefore represents the final way in which nitrogenous waste is excreted in mammals. Transported to the blood, it is filtered into the kidneys and then excreted in the urine, but is therefore not reused. Therefore, obtaining nitrogen poses a major challenge during hibernation. How do hibernators adapt? The team of Matthew Regan of the University of Wisconsin-Madison in the United States studied the role of the intestinal microbiota in the recycling of urea nitrogen during hibernation. They found that in scratched squirrels, certain bacteria were crucial in the re-incorporation of nitrogen.

In most hibernators, the consequence of nitrogen deficiency leads to loss of muscle mass, an awakening problem not faced by the ground squirrel, a wintering rodent native to North America. We knew that the urea produced by this animal is metabolized by certain intestinal microorganisms that extract their own sources of nitrogen. However, it was not known whether this urea nitrogen released by the microbiota could be recycled in the metabolism of these terrestrial squirrels in order to compensate for nitrogen deficiencies. To answer this question, scientists injected urea labeled with carbon and nitrogen isotopes traceable into the blood of terrestrial squirrels at different times of the year: during the summer, at the beginning of hibernation, and at the end of the year. winter. They also treated some animals with antibiotics to remove some of the microorganisms from their gut microbiota. This allowed them to compare the response of rodents with the microbiota intact or depleted.

Thanks to isotopic labeling, scientists tracked the process of nitrogen metabolism between the host and its microbiota. They showed that the incorporation of labeled nitrogen (from the degradation of injected urea) into the proteins of ground squirrel tissue tissues was higher in late winter, suggesting that nitrogen recovery increases as fasting continues. This is possible due to a higher capacity of urea transport from the blood to the intestinal lumen thanks to a greater expression, and therefore a greater number, of urea transporters (UTB) in winter compared to the time. activates animals. In contrast, labeled nitrogen was less present in the tissues of animals with depleted microbiota. Therefore, nitrogen recycling seems to depend on the presence of intestinal microorganisms.

The team then focused on the expression of urease, an enzyme that is not produced by animals, but specifically expressed by certain intestinal microorganisms. This enzyme hydrolyzes urea to ammonia (NH3) and carbon dioxide (CO2). After sequencing the genome of the bacteria present in the gut of rodents, the researchers found that the increased expression of urease genes coincided with the incorporation of nitrogen (in its hydrolyzed form of ammonia) by part of the ground squirrels during the winter season. Therefore, it appears that the host and its microbiota have co-evolved into a close symbiotic relationship in which the host benefits from the ureolytic activity of its intestinal bacteria to re-incorporate nitrogen during periods of hypometabolism.

Researchers do not rule out the existence of similar mechanisms in other mammals, including humans. These results could pave the way for potential applications designed to promote the maintenance of muscle mass during aging.

A rodent that recycles nitrogen for wintering

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