From: University of Colorado Denver
Posted: Thursday, April 21, 2016
In a discovery with implications for long-term spaceflight and future missions to Mars, a researcher at the University of Colorado Anschutz Medical Campus has found that mice flown aboard the space shuttle Atlantis returned to Earth with early signs of liver disease.
"Prior to this study we really didn't have much information on the impact of spaceflight on the liver," said the study's lead author Karen Jonscher, PhD, an associate professor of anesthesiology and a physicist at CU Anschutz. "We knew that astronauts often returned with diabetes-like symptoms but they usually resolved quickly."
But the prospect of liver damage raises new concerns.
The mice studied spent 13.5 days aboard the space shuttle. When they returned, Jonscher and her colleagues were able to collect liver samples. They found that spaceflight appeared to activate specialized liver cells that may go on to induce scarring and cause long-term damage to the organ.
"We saw the beginning of nascent liver damage in just 13.5 days," Jonscher said. "The mice also lost lean muscle mass. We have seen this same phenomenon in humans on bedrest - muscles atrophy and proteins break down into amino acids. The question is, how does that affect your liver?"
For years scientists have studied the impact of spaceflight on human physiology but most of the research has focused on bone, muscle, brain and cardiovascular function. Yet studies suggesting that astronauts who spent time in space developed diabetes-like symptoms link microgravity with metabolism and point toward the liver, the major organ of metabolism, as a possible target of the space environment.
Whether or not the liver itself is vulnerable to damage has remained an open question. And this research may help answer that.
The mice spent time orbiting the Earth on the final space shuttle flight in 2011. Once they returned home, teams of scientists were allowed to share and study their internal organs.
Jonscher's team found that spaceflight resulted in increased fat storage in the liver, comparing pair-fed mice on Earth to those on the shuttle. This was accompanied by a loss of retinol, an animal form of Vitamin A, and changes to levels of genes responsible for breaking down fats. As a result, mice showed signs of nonalcoholic fatty liver disease (NAFLD) and potential early indicators for the beginnings of fibrosis, which can be one of the more progressive consequences of NAFLD.
"It generally takes a long time, months to years, to induce fibrosis in mice, even when eating an unhealthy diet," Jonscher said. "If a mouse is showing nascent signs of fibrosis without a change in diet after 13 ½ days, what is happening to the humans?"
With NASA planning longer deep space missions, including one to Mars which would take at least a year, these findings are significant.
"Whether or not this is a problem is an open question," Jonscher said. "We need to look at mice involved in longer duration space flight to see if there are compensatory mechanisms that come into play that might protect them from serious damage."
She pointed out that the stress of spaceflight and reentry to Earth might have also played a role in the liver damage.
"Further study in this area is merited and analysis of tissues harvested in space from mice flown aboard the International Space Station for several months may help determine whether long-term spaceflight might lead to more advanced hepatic injury and whether damage can be prevented," she said.
The study was published Wednesday in the journal PLOS ONE.
Spaceflight affects numerous organ systems in the body, leading to metabolic dysfunction that may have long-term consequences. Microgravity-induced alterations in liver metabolism, particularly with respect to lipids, remain largely unexplored. Here we utilize a novel systems biology approach, combining metabolomics and transcriptomics with advanced Raman microscopy, to investigate altered hepatic lipid metabolism in mice following short duration spaceflight. Mice flown aboard Space Transportation System -135, the last Shuttle mission, lose weight but redistribute lipids, particularly to the liver. Intriguingly, spaceflight mice lose retinol from lipid droplets. Both mRNA and metabolite changes suggest the retinol loss is linked to activation of PPARα-mediated pathways and potentially to hepatic stellate cell activation, both of which may be coincident with increased bile acids and early signs of liver injury. Although the 13-day flight duration is too short for frank fibrosis to develop, the retinol loss plus changes in markers of extracellular matrix remodeling raise the concern that longer duration exposure to the space environment may result in progressive liver damage, increasing the risk for nonalcoholic fatty liver disease.
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