Link to the paper: https://www.sciencedirect.com/…/pii/S2589004222014857

The paper investigates the transcriptome response of the liver and quadriceps in mice during spaceflight, using GSEA, ORA, and sparse partial least square-differential analysis. It is found that impaired lipid metabolism gene expression in the liver and muscle atrophy gene expression are two paired events during spaceflight, with a specific gene cluster in the liver correlating with glucose sparing and energy-saving response affecting high energy demand processes in the muscle. Dietary changes are suggested as a possible countermeasure.

The study highlights the importance of discriminating genes over differentially expressed genes (DEGs) in deciphering omic data. Lipid metabolism gene expression in the liver is found to correlate with insulin signaling and glucose metabolism gene expression in the quadriceps during spaceflight. A cluster of lipid metabolism-related genes in the liver is identified, which correlates the most with glucose transport gene expression and potentially insulin resistance in the muscle. Sestrin 1, a regulator of cell metabolism, is also found to be a discriminating gene in both the liver and quadriceps.

Contributions of the Paper

The paper investigates the transcriptome response of the liver and quadriceps in mice during spaceflight, revealing impaired lipid metabolism gene expression in the liver and muscle atrophy gene expression as paired events during spaceflight. Dietary changes are suggested as a possible countermeasure.

The study highlights the importance of discriminating genes over differentially expressed genes (DEGs) in deciphering omic data. It identifies a cluster of lipid metabolism-related genes in the liver that correlates with glucose transport gene expression and potentially insulin resistance in the muscle. Sestrin 1, a regulator of cell metabolism, is also found to be a discriminating gene in both the liver and quadriceps.

The findings provide insights into the metabolic crosstalk between the liver and muscle during spaceflight and suggest a starvation-like phenotype promoting a metabolic shift towards energy-saving mode and lipid mobilization. The study proposes dietary changes, such as starch supplementation and microbiome modulation, as affordable and sustainable countermeasures to support planetary goals and outer space settlement.

Practical Implications of the Paper

The findings of this study have practical implications for understanding the physiological changes that occur in the liver and muscle during spaceflight. Impaired lipid metabolism gene expression in the liver and muscle atrophy gene expression are identified as paired events during spaceflight, highlighting the need for countermeasures to mitigate these effects. Dietary changes, such as starch supplementation and microbiome modulation, are suggested as potential strategies to address these issues and support the health of astronauts during space missions.

The study also emphasizes the importance of monitoring astronaut health and ensuring the safety of future habitable space missions. Molecular analyses, such as transcriptome profiling, can provide valuable insights into the molecular mechanisms underlying physiological changes in space. This knowledge can inform the development of targeted interventions and countermeasures to mitigate the risks associated with spaceflight, particularly muscle atrophy and metabolic dysregulation.

Furthermore, the identification of specific gene clusters and pathways related to lipid metabolism and glucose sparing provides potential targets for further research and intervention development. Understanding the metabolic crosstalk between the liver and muscle during spaceflight can contribute to the development of personalized nutrition and exercise regimens to optimize astronaut health and performance in space.

Methods used in this paper

The study was conducted aboard the International Space Station (ISS) in 2014 using twelve female C57BL6J mice, with six mice in the flight group and six in the ground control group. The mice were exposed to spaceflight for 37 days and maintained on a 12-hour day-night cycle, with Nutrient Upgraded Rodent Food Bar (NuRFB) as their diet.

The research platform used for the experiment was NASA’s Rodent Research Hardware System, also known as the Rodent Research Habitat System.

The mice were sacrificed on orbit on the ISS for the flight group and on the ground at the same time for the ground control group. The entire carcasses of ten mice were stored at -80°C until processing.

RNA extraction from 20-30mg of mice liver and muscle was performed using a lysis buffer and beta-mercaptoethanol. The RNA was further purified using the Qiagen AllPrep DNARNA Mini Kit, and RNA concentrations were measured using the NanoDrop 2000 UV-Vis Spectrophotometer.

RNA sequencing and library construction were performed on 1 mg of RNA with RIN values of 7 or above, using the Illumina HiSeq 4000 kit and experimental protocol.

Data used in this paper

The study utilized transcriptome data from the liver and quadriceps muscles of mice that were exposed to spaceflight for 37 days on the NASA RR1 mission.

The data was obtained from RNA sequencing and library construction using the Illumina HiSeq 4000 kit and experimental protocol.

Raw FASTQ files from the dataset were processed using the “GeneLab RNAseq data processing protocol”.

The quantification data was imported to R (version 3.6.0) for further analysis.

The study compared the transcriptome response of the liver and quadriceps muscles between the flight group and the ground control group of mice.

The data analysis involved techniques such as Gene Set Enrichment Analysis (GSEA), Over-Representation Analysis (ORA), and sparse partial least square-differential analysis.

Note: The sources do not provide specific details about the size or characteristics of the dataset used in the study.

Results of the paper

The study found that lipid metabolism is the most affected biological process in both the liver and quadriceps muscles during spaceflight.

Gene expression patterns in the liver were strongly correlated with glucose sparing and an energy-saving response, affecting high energy demand processes in the muscle, such as DNA repair, autophagy, and translation.

Impaired lipid metabolism gene expression in the liver and muscle atrophy gene expression were identified as paired events during spaceflight.

The study also reported that mitochondria-related processes were upregulated in the liver but downregulated in the quadriceps, potentially suggesting impaired protein metabolism.

Note: The sources do not provide specific numerical data or statistical analysis of the results.

We value your ideas and feel free to comment below.