Scientists use cavefish to learn more about metabolism and the evolutionary basis of being a couch potato

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Cross section of muscle cells for surface fish and cavefish from the caves of Pachón and Tinaja. Muscle fibers are shown in pink and fat deposits are white. Credit: Stowers Institute for Medical Research

Stay-at-home orders issued at the start of the COVID-19 pandemic ushered in food hoarding and a surge in digital entertainment subscriptions, restaurant takeout and delivery services – a perfect storm for a collective couch potato phenomenon. Now researchers have discovered what prolonged physical inactivity could mean for humans many thousands of years down the road by studying cavefish.


The Stowers Institute for Medical Research has reported new research on adaptations in cavefish metabolism that occurred when Mexican river tetrafish 160,000 years ago streamed into underground caves and sheltered in place ever since. The study, published in PNAS on Jan. 24, 2023, led by predoctoral researcher Luke Olsen in the lab of Associate Investigator Nicolas Rohner, Ph.D., found that cavefish muscle metabolism had undergone genetic reprogramming, resulting in radical changes in physiology, morphology and behavior.

Despite striking changes in appearance, the cavefish remained healthy both in the wild and in the lab. Studying cavefish muscle metabolism from an evolutionary perspective can thus provide us with insight into the influence of increasing inactivity on humans.

“It’s no surprise that people move less and less as technology advances,” Rohner said. “With cavefish, we have a unique system that allows us to study what might happen if people sit on the couch for a very, very long time.”

“It’s no surprise that people move less and less as technology advances,” says Rohner. “With cavefish, we have a unique system that allows us to study what might happen if people stay on the couch for a very, very long time.” Credit: Stowers Institute for Medical Research

A sedentary lifestyle can be detrimental to human health, promoting muscle loss and weight gain, often leading to conditions such as diabetes, heart disease and stroke. In examining cavefish, the team found something paradoxical.

Cavefish populations from central Mexico showed reduced muscle mass and increased fat, 30 and 40 percent, respectively, compared to surface fish. Not only did this not affect their health, but cavefish could swim just as fast as their “fit” surface fish cousins, and for a long time, via genetic changes in muscle metabolism.

“If you look inside a cavefish muscle cell, there’s a clear change in the composition and therefore function of muscle fibers,” Olsen said. “And in the lab, we’ve controlled for every environmental variable, but we’re still seeing very different muscle structure in cavefish, suggesting a genetic component behind the fatty fish phenotype.”

Stowers scientists use cavefish to learn more about metabolism and the evolutionary basis of being a couch potato

Morphological differences between surface fish (top left) and cavefish from the Tinaja and Pachón Caves of central Mexico (center, bottom right). Credit: Stowers Institute for Medical Research

Researchers focused on genetics and discovered a significant reduction in the activity of genes encoding proteins required for muscle contraction. At the same time, the activity of a master gene that regulates fat cell development and metabolism was increased. To determine whether these changes were indeed genetic, the team designed a swim test to examine how cavefish respond to stimulation.

They found that normal swimming speed was nearly four times lower for cavefish; however, when stimulated, they not only increased their speed to speeds comparable to surface fish, but could also maintain the pace for long periods of time, indicating muscular endurance.

“At first I didn’t understand how this was possible because the cavefish didn’t have the right ‘machinery’ for muscle contraction,” Olsen said. “Then we realized they had adapted a different mechanism for using energy stored in muscles.”

Indeed, cavefish had elevated levels of an enzyme responsible for the formation and metabolism of glycogen, a complex formed from glucose. In addition, this enzyme has a particular site susceptible to the addition of a phosphate molecule, or phosphorylation, which was not observed in surface fish. When phosphorylated, glycogen synthesis and storage is enhanced and when not, the enzyme switches to a glycogen metabolism pathway required for sustained muscle contraction.

Understanding how cavefish metabolisms have evolved over hundreds of thousands of years can illuminate how humans can adapt over long periods of time.

“In the future, for example during space travel to other planets or even galaxies, having an evolutionary model system with the natural variation we see in humans could inform us about which genes play a role during extended periods of inactivity and whether there are conserved molecular pathways. that drive shifts in energy investment strategies without corresponding pathologies,” Rohner said.

More information:
Luke Olsen et al, Metabolic reprogramming underlies cavefish muscular endurance despite loss of muscle mass and contractility, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2204427120

Provided by Stowers Institute for Medical Research

Quote: Scientists use cavefish to learn more about metabolism and the evolutionary basis of being a couch potato (2023, January 24) Retrieved January 25, 2023 from https://phys.org/news/2023-01-scientists-cavefish- metabolism-evolutionary-base.html

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