Space Rats Used to Pioneer Liver Disease Research

By Cai McCann

Artwork by Corinne Atkinson

You might be familiar with spaceflight being the newest frontier for humans. But, did you know the health effects of spaceflight on humans? In recent years, the science world has just begun to explore the physiological consequences, through investigating factors of microgravity, radiation, carbon dioxide, and more. The study of these limits not only gives stock to the human’s physiological limits but also provides important insights on how feasible living in space actually is.


In a 2016 study (Jonscher et al. 2016), researchers sought to detect molecular-level changes in the liver, which can characterize nonalcoholic fatty liver disease (NAFLD). NAFLD is associated with irreversible tissue damage and increased risk of cardiovascular events, type 2 diabetes and liver cancer (Jonscher et al. 2016). The researchers flew nine-week-old mice up into space for 13 days with the Space Transportation System -135, to the International Space Station. They then recorded a series of measurements of the subsequent liver biopsies, including measurements of the biomolecules of the liver, proteins, and other chemicals produced by the liver during the time.


From these different experiments, they discovered that the mice lost more lean body mass and increased fat as a percentage of body weight compared to the controls (Jonscher et al. 2016). Spaceflight mice increased percent body fat by accumulating components of fats, such as hepatic lipid droplets and total triglycerides, ~3.5-fold compared with controls (Jonscher et al. 2016). Additionally, the spaceflight mice concentrations of choline, choline phosphate and glycerophosphocholine are decreased, while betaine, a molecular product of metabolism associated with synthesis and transport of lipids. Spaceflight mice have less abundant large, non-membrane bound droplets in their livers yet also the decreases in choline, choline phosphate and glycerophosphocholine could indicate that cell membrane material is diverted to making new or larger triglyceride-packed lipid droplets, i.e. fat storage, instead of building cell membranes in the body.


Further, the mice experienced increased expression or decreased expression of key genes associated with biosynthesis of fats, such as triglyceride biosynthesis (Jonscher et al. 2016). For example, spaceflight mice upregulated genes that contribute to cell membrane building, such as adding triglycerides or hepatic carnitine palmitoyltransferase-1a (Cpt1a) enzymes that are involved in transporting fatty acids (a component of fats) for metabolism. These data were intriguing because they suggest that spaceflight shifts the balance between creating new fatty molecules and metabolizing them to compensate for spaceflight stressors.


Simply stated, by increasing fatty molecule storage, the mice’s bodies may better protect against an overload of toxic products induced by the stresses of space travel. However, this protective effect comes with a tradeoff. Space mice increased the gene subset corresponding to metabolites, specifically, the majority of genes mapped to metabolic pathways, in particular to fat digestion and absorption (Jonscher et al. 2016). This increase means greater storage of fatty molecules, potentially leading to early NAFLD. These data are preliminary and researchers anticipate further work to study these metabolic pathways and ways to prevent the tissue damage of NAFLD.


So, what if we lived in space? If you take anything from this article, realize that the research is progressing at a furious pace but much remains unanswered. The next time you are deliberating on whether to hop on that spacecraft, consider this: yes, as a space traveler, you may potentially gain weight and be more susceptible to certain diseases, but there may have been more research on preventative measures and more studies in humans rather than just mice. If we have shift towards alternate ways of living in space and potentially more physiologically stressful, our body may meet the demand, developing innovative responses.


Okay, what’s your next move—to space? It is crucial to weigh the benefits from all sides, and maybe you will find yourself hopping on that spacecraft in 50 years.


References:


Jonscher KR, Alfonso-Garcia A, Suhalim JL, Orlicky DJ, Potma EO, Ferguson VL, et al. (2016) Spaceflight Activates Lipotoxic Pathways in Mouse Liver. PLoS ONE 11(4): e0152877. doi:10.1371/ journal.pone.0152877

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