Spaceflight Activates Lipotoxic Pathways in Mouse Liver.
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.
Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of America.
Karen R
KR
Jonscher
Department of Biomedical Engineering, University of California Irvine, Irvine, CA, United States of America.
Alba
A
Alfonso-Garcia
Department of Biomedical Engineering, University of California Irvine, Irvine, CA, United States of America.|Beckman Laser Institute and Medical Clinic, University of California Irvine, Irvine, CA, United States of America.
Jeffrey L
JL
Suhalim
Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of America.
David J
DJ
Orlicky
Beckman Laser Institute and Medical Clinic, University of California Irvine, Irvine, CA, United States of America.
Eric O
EO
Potma
Department of Mechanical Engineering, University of Colorado at Boulder, Boulder, CO, United States of America.
Virginia L
VL
Ferguson
Department of Orthopedic Surgery, Harvard Medical School, Boston, MA, United States of America.
Mary L
ML
Bouxsein
Department of Bioengineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.
Ted A
TA
Bateman
BioServe Space Technologies, University of Colorado at Boulder, Boulder, CO, United States of America.
Louis S
LS
Stodieck
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of America.
Moshe
M
Levi
Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of America.
Jacob E
JE
Friedman
Department of Basic Sciences, Division of Radiation Research, Loma Linda University School of Medicine, Loma Linda, CA, United States of America.
Daila S
DS
Gridley
Department of Basic Sciences, Division of Radiation Research, Loma Linda University School of Medicine, Loma Linda, CA, United States of America.
Michael J
MJ
Pecaut
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight; D005260:Female; D020869:Gene Expression Profiling; D055166:Hepatic Stellate Cells / Q000378:metabolism; D066292:Lipid Droplets / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D055432:Metabolomics; D051379:Mice; D008810:Mice, Inbred C57BL; D047493:PPAR alpha / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013026:Space Flight; D049490:Systems Biology
D015415:Biomarkers; D047493:PPAR alpha; D012333:RNA, Messenger