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Single swim sessions in C. elegans induce key features of mammalian exercise

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ABSTRACT

Background: Exercise exerts remarkably powerful effects on metabolism and health, with anti-disease and anti-aging outcomes. Pharmacological manipulation of exercise benefit circuits might improve the health of the sedentary and the aging populations. Still, how exercised muscle signals to induce system-wide health improvement remains poorly understood. With a long-term interest in interventions that promote animal-wide health improvement, we sought to define exercise options for Caenorhabditis elegans.

Results: Here, we report on the impact of single swim sessions on C. elegans physiology. We used microcalorimetry to show that C. elegans swimming has a greater energy cost than crawling. Animals that swam continuously for 90 min specifically consumed muscle fat supplies and exhibited post-swim locomotory fatigue, with both muscle fat depletion and fatigue indicators recovering within 1 hour of exercise cessation. Quantitative polymerase chain reaction (qPCR) transcript analyses also suggested an increase in fat metabolism during the swim, followed by the downregulation of specific carbohydrate metabolism transcripts in the hours post-exercise. During a 90 min swim, muscle mitochondria matrix environments became more oxidized, as visualized by a localized mitochondrial reduction-oxidation-sensitive green fluorescent protein reporter. qPCR data supported specific transcriptional changes in oxidative stress defense genes during and immediately after a swim. Consistent with potential antioxidant defense induction, we found that a single swim session sufficed to confer protection against juglone-induced oxidative stress inflicted 4 hours post-exercise.

Conclusions: In addition to showing that even a single swim exercise bout confers physiological changes that increase robustness, our data reveal that acute swimming-induced changes share common features with some acute exercise responses reported in humans. Overall, our data validate an easily implemented swim experience as C. elegans exercise, setting the foundation for exploiting the experimental advantages of this model to genetically or pharmacologically identify the exercise-associated molecules and signaling pathways that confer system-wide health benefits.

Electronic supplementary material: The online version of this article (doi:10.1186/s12915-017-0368-4) contains supplementary material, which is available to authorized users.

No MeSH data available.


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Transcriptional changes in C. elegans are consistent with reduced glucose metabolism after swim exercise. a Diagram of glucose metabolism highlighting the steps that we chose for our expression analysis. C. elegans proteins are shown in red. For simplicity, several metabolic steps are omitted. b Heat map summarizing quantitative polymerase chain reaction results in N2 animals at different time points post-exercise for glucose metabolic genes (n = 5 independent trials). Expression data is presented as log2 fold change of exercise samples relative to control samples in a color gradient from red (downregulation) to white (no change). Paired two-tailed Student’s t tests were used to compare relative expressions of control versus exercise samples at each time point. See Additional file 5 for detailed results for each gene. **P < 0.01; ***P < 0.001; ****P < 0.0001
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Fig4: Transcriptional changes in C. elegans are consistent with reduced glucose metabolism after swim exercise. a Diagram of glucose metabolism highlighting the steps that we chose for our expression analysis. C. elegans proteins are shown in red. For simplicity, several metabolic steps are omitted. b Heat map summarizing quantitative polymerase chain reaction results in N2 animals at different time points post-exercise for glucose metabolic genes (n = 5 independent trials). Expression data is presented as log2 fold change of exercise samples relative to control samples in a color gradient from red (downregulation) to white (no change). Paired two-tailed Student’s t tests were used to compare relative expressions of control versus exercise samples at each time point. See Additional file 5 for detailed results for each gene. **P < 0.01; ***P < 0.001; ****P < 0.0001

Mentions: The two main sources of energy during physical exercise are carbohydrates and fats. Therefore, we analyzed how acute swim exercise might affect gene expression of key members of both C. elegans carbohydrate and fat metabolism. To evaluate potential carbohydrate utilization, we focused our analysis on glucose metabolism: glucose transport, glycolysis, and gluconeogenesis (Fig. 4a). We found persistent downregulation of transcript levels of the main C. elegans glucose transporter, encoded by fgt-1, between 1 and 4 hours post-exercise (Fig. 4b; Additional file 5A). Expression of three essential glycolytic enzymes was also significantly downregulated in exercised animals at different time points: hxk-2, hexokinase (first enzyme of glycolysis); pfk-1.1, phosphofructokinase (rate-limiting enzyme of glycolysis); and pyk-1 and pyk-2, pyruvate kinases (last enzymes of glycolysis) (Fig. 4b; Additional file 5B–E). ldh-1, encoding the B subunit of lactate dehydrogenase, which catalyzes the interconversion of pyruvate and lactate in a post-glycolysis process, was also downregulated between 1 and 4 hours after swim exercise (Fig. 4b; Additional file 5F). Finally, a similar temporal pattern of downregulation was observed for pck-1, a phosphoenolpyruvate carboxykinase that is the rate-limiting enzyme of gluconeogenesis (Fig. 4b; Additional file 5G; magnitude of downregulation greater for pck-1). The shared theme of expression downregulation of seven out of seven selected genes indicates that glucose metabolism as a whole may be reduced in the hours following acute swim exercise.Fig. 4


Single swim sessions in C. elegans induce key features of mammalian exercise
Transcriptional changes in C. elegans are consistent with reduced glucose metabolism after swim exercise. a Diagram of glucose metabolism highlighting the steps that we chose for our expression analysis. C. elegans proteins are shown in red. For simplicity, several metabolic steps are omitted. b Heat map summarizing quantitative polymerase chain reaction results in N2 animals at different time points post-exercise for glucose metabolic genes (n = 5 independent trials). Expression data is presented as log2 fold change of exercise samples relative to control samples in a color gradient from red (downregulation) to white (no change). Paired two-tailed Student’s t tests were used to compare relative expressions of control versus exercise samples at each time point. See Additional file 5 for detailed results for each gene. **P < 0.01; ***P < 0.001; ****P < 0.0001
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5385602&req=5

Fig4: Transcriptional changes in C. elegans are consistent with reduced glucose metabolism after swim exercise. a Diagram of glucose metabolism highlighting the steps that we chose for our expression analysis. C. elegans proteins are shown in red. For simplicity, several metabolic steps are omitted. b Heat map summarizing quantitative polymerase chain reaction results in N2 animals at different time points post-exercise for glucose metabolic genes (n = 5 independent trials). Expression data is presented as log2 fold change of exercise samples relative to control samples in a color gradient from red (downregulation) to white (no change). Paired two-tailed Student’s t tests were used to compare relative expressions of control versus exercise samples at each time point. See Additional file 5 for detailed results for each gene. **P < 0.01; ***P < 0.001; ****P < 0.0001
Mentions: The two main sources of energy during physical exercise are carbohydrates and fats. Therefore, we analyzed how acute swim exercise might affect gene expression of key members of both C. elegans carbohydrate and fat metabolism. To evaluate potential carbohydrate utilization, we focused our analysis on glucose metabolism: glucose transport, glycolysis, and gluconeogenesis (Fig. 4a). We found persistent downregulation of transcript levels of the main C. elegans glucose transporter, encoded by fgt-1, between 1 and 4 hours post-exercise (Fig. 4b; Additional file 5A). Expression of three essential glycolytic enzymes was also significantly downregulated in exercised animals at different time points: hxk-2, hexokinase (first enzyme of glycolysis); pfk-1.1, phosphofructokinase (rate-limiting enzyme of glycolysis); and pyk-1 and pyk-2, pyruvate kinases (last enzymes of glycolysis) (Fig. 4b; Additional file 5B–E). ldh-1, encoding the B subunit of lactate dehydrogenase, which catalyzes the interconversion of pyruvate and lactate in a post-glycolysis process, was also downregulated between 1 and 4 hours after swim exercise (Fig. 4b; Additional file 5F). Finally, a similar temporal pattern of downregulation was observed for pck-1, a phosphoenolpyruvate carboxykinase that is the rate-limiting enzyme of gluconeogenesis (Fig. 4b; Additional file 5G; magnitude of downregulation greater for pck-1). The shared theme of expression downregulation of seven out of seven selected genes indicates that glucose metabolism as a whole may be reduced in the hours following acute swim exercise.Fig. 4

View Article: PubMed Central - PubMed

ABSTRACT

Background: Exercise exerts remarkably powerful effects on metabolism and health, with anti-disease and anti-aging outcomes. Pharmacological manipulation of exercise benefit circuits might improve the health of the sedentary and the aging populations. Still, how exercised muscle signals to induce system-wide health improvement remains poorly understood. With a long-term interest in interventions that promote animal-wide health improvement, we sought to define exercise options for Caenorhabditis elegans.

Results: Here, we report on the impact of single swim sessions on C. elegans physiology. We used microcalorimetry to show that C. elegans swimming has a greater energy cost than crawling. Animals that swam continuously for 90&nbsp;min specifically consumed muscle fat supplies and exhibited post-swim locomotory fatigue, with both muscle fat depletion and fatigue indicators recovering within 1&nbsp;hour of exercise cessation. Quantitative polymerase chain reaction (qPCR) transcript analyses also suggested an increase in fat metabolism during the swim, followed by the downregulation of specific carbohydrate metabolism transcripts in the hours post-exercise. During a 90&nbsp;min swim, muscle mitochondria matrix environments became more oxidized, as visualized by a localized mitochondrial reduction-oxidation-sensitive green fluorescent protein reporter. qPCR data supported specific transcriptional changes in oxidative stress defense genes during and immediately after a swim. Consistent with potential antioxidant defense induction, we found that a single swim session sufficed to confer protection against juglone-induced oxidative stress inflicted 4&nbsp;hours post-exercise.

Conclusions: In addition to showing that even a single swim exercise bout confers physiological changes that increase robustness, our data reveal that acute swimming-induced changes share common features with some acute exercise responses reported in humans. Overall, our data validate an easily implemented swim experience as C. elegans exercise, setting the foundation for exploiting the experimental advantages of this model to genetically or pharmacologically identify the exercise-associated molecules and signaling pathways that confer system-wide health benefits.

Electronic supplementary material: The online version of this article (doi:10.1186/s12915-017-0368-4) contains supplementary material, which is available to authorized users.

No MeSH data available.


Related in: MedlinePlus