Spaceflight Activates Lipotoxic Pathways in Mouse Liver

• Published in: PloS one Vol. 11; no. 4; p. e0152877
• Main Authors: Jonscher, Karen R., Alfonso-Garcia, Alba, Suhalim, Jeffrey L., Orlicky, David J., Potma, Eric O., Ferguson, Virginia L., Bouxsein, Mary L., Bateman, Ted A., Stodieck, Louis S., Levi, Moshe, Friedman, Jacob E., Gridley, Daila S., Pecaut, Michael J.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.04.2016; Public Library of Science (PLoS)
• Subjects: Aerospace environments; Animals; Bile; Bile acids; Biology and Life Sciences; Biomarkers - metabolism; Biomedical engineering; Body Weight; Bone surgery; Cell activation; Extracellular matrix; Fatty liver; Female; Fibrosis; Gene Expression Profiling; Genotype & phenotype; Health aspects; Health risks; Hepatic Stellate Cells - metabolism; Homeostasis; Laboratory animals; Lipid Droplets - metabolism; Lipid metabolism; Lipids; Liver; Liver - cytology; Liver - metabolism; Liver diseases; Medicine and Health Sciences; Metabolic diseases; Metabolism; Metabolites; Metabolomics; Mice; Mice, Inbred C57BL; Microgravity; Microscopy; Oxidative stress; Physical Sciences; PPAR alpha - metabolism; Risk factors; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Space Flight; Space shuttles; Space transportation system; Studies; Systems Biology; Transportation systems; Vitamin A; United States
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0152877

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.