Harnessing the gut microbiota to facilitate muscle protein synthesis during fasting hibernation.

Physiology in Focus 2024 (Northumbria University, UK) (2024) Proc Physiol Soc 59, SA03

Research Symposium: Harnessing the gut microbiota to facilitate muscle protein synthesis during fasting hibernation.

Matthew Regan1, Garret Suen1, Fariba Assadi-Porter1, Hannah Carey1,

1University of Montreal Montreal Canada, 2University of Wisconsin-Madison Madison United States, 3University of Wisconsin-Madison Madison United States,

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Hibernation is a mammalian adaptation to wintertime food scarcity. It is the net manifestation of multiple underlying traits, and the most important of these is torpor, a regulated depression of metabolism that reduces wintertime metabolic rate – and thus energy use – by up to 98% relative to basal summertime rates. This allows hibernators to forego eating and rely entirely on stored fat for multiple months at a time, effectively solving the food scarcity problem. However, in the process, hibernation presents the animal with an array of “collateral” challenges to which they have needed to evolve resilience. One of these challenges is the risk of muscle atrophy, which arises from the combined effects of fasting and inactivity that typify the hibernation season. It has been known for over 20 years that hibernating mammals are resistant to muscle atrophy, but the mechanisms underlying this resistance, including the cellular mechanisms of protein balance and the continued supply of nitrogen despite the lack of exogenous source, are still being resolved. Recently, we have shown that hibernating ground squirrels obtain nitrogen during the winter fast by salvaging the nitrogen atoms present in urea using a gut microbe-dependent process called urea nitrogen salvage (UNS). The microbially liberated urea nitrogen is subsequently absorbed and incorporated into the protein content of liver and skeletal muscle, a process that progressively increases from the summer active season to early winter, and then peaks in late winter just prior to spring emergence. We are now in the process of characterizing which proteins in the skeletal muscle and heart are synthesized with the aid of UNS. We are conducting this project in the context of possible countermeasure development for spaceflight-induced disuse atrophy, as it is known that humans are capable of using UNS under certain conditions. This suggests that the necessary machinery for UNS is in present in humans, and so the mechanisms by which hibernators optimize their machinery to maximize UNS late in the hibernation season may provide insight into how our own UNS machinery may be optimized. This could potentially benefit humans under a variety of muscle atrophying conditions, particularly those in which limited nitrogen supply is a factor.



Where applicable, experiments conform with Society ethical requirements.

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