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Remarkable metabolic reorganization and altered metabolic requirements in frog metamorphic climax
Bin Wang
Chengdu Institute of Biology, CAS
Corresponding Author
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This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Frontiers in Zoology.
Background Metamorphic climax is the crucial stage of amphibian metamorphosis responsible for the morphological and functional changes necessary for transition to a terrestrial habitat. This developmental period is sensitive to environmental changes and pollution. Understanding its metabolic basis and requirements is significant for ecological and toxicological research. Rana omeimontis tadpoles are a useful model for investigating this stage as their liver is involved in both metabolic regulation and fat storage.
Results We used a combined approach of transcriptomics and metabolomics to study the metabolic reorganization during natural and T3-driven metamorphic climax in the liver and tail of Rana omeimontis tadpoles. The metabolic flux from the apoptotic tail replaced hepatic fat storage as metabolic fuel, resulting in increased hepatic amino acid and fat levels. In the liver, amino acid catabolism (transamination and urea cycle) was upregulated along with energy metabolism (TCA cycle and oxidative phosphorylation), while the carbohydrate and lipid catabolism (glycolysis, pentose phosphate pathway (PPP), and β-oxidation) decreased. The hepatic glycogen phosphorylation and gluconeogenesis were upregulated, and the carbohydrate flux was used for synthesis of glycan units (e.g., UDP-glucuronate). In the tail, glycolysis, β-oxidation, and transamination were all downregulated, accompanied by synchronous downregulation of energy production and consumption. Glycogenolysis was maintained in the tail, and the carbohydrate flux likely flowed into both PPP and the synthesis of glycan units (e.g., UDP-glucuronate and UDP-glucosamine). Fatty acid elongation and desaturation, as well as the synthesis of bioactive lipid (e.g., prostaglandins) were encouraged in the tail during metamorphic climax. Protein synthesis was downregulated in both the liver and tail. The significance of these metabolic adjustments and their potential regulation mechanism are discussed.
Conclusion The energic strategy and anabolic requirements during metamorphic climax were revealed at the molecular level. Amino acid made an increased contribution to energy metabolism during metamorphic climax. Carbohydrate anabolism was essential for the body construction of the froglets. The tail was critical in anabolism including synthesizing bioactive metabolites. These findings increase our understanding of amphibian metamorphosis and provide background information for ecological, evolutionary, conservation, and developmental studies of amphibians.
Keywords
Amphibian, Metabolic reorganization, Metabolic switch, Metamorphosis
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This is a list of supplementary files associated with this preprint. Click to download.
- Additionalfile1.xlsx
Additional file 1: Liver and tail metabolites tables.
- Additionalfile2.pdf
Additional file 2: Figure S1 Overview of the transcriptomes of control and T3-treated tadpoles. (A) Unigene length distribution. (B) Gene expression correlations between samples. (C–D) Volcano plots showing the DEGs of liver (C) and tail (D) metabolomes between control and T3-treated tadpoles. Figure S2 Liver size of control and T3-treated tadpoles. ***, p < 0.001. Figure S3 Scatter plots of PCAs based on liver (A) and tail (B) metabolomes of pro-metamorphic (stage 30-31) and T3-driven metamorphic tadpoles. Figure S4 Transcriptional variation of genes involved in primary bile acid biosynthesis and steroid metabolism in the liver. *, p < 0.05; **, p < 0.01; ***, p < 0.001. Figure S5 Transcriptional variation of genes with potential metabolic regulatory functions in the liver and tail. *, p < 0.05. Figure S6 Arachidonic acid metabolism highlighted by tail DEGs between control and T3-treated tadpoles. Figure S7 Variation of glutamine levels during metamorphic climax. Different letters denote significant differences between groups (p < 0.05), as shown by the Student–Newman–Keuls post hoc test after one-way ANOVA. *, p < 0.05. Figure S8 Transcriptional changes of genes involved in energy metabolism during metamorphic climax. (A) Transcriptional changes of genes involved in energy metabolism (TCA cycle and oxidative phosphorylation) in the liver. (B) Transcriptional changes of genes involved in TCA cycle in the tail. (C) Heatmap showing the transcriptional level of genes involved in oxidative phosphorylation in the tail. (D) Transcriptional changes of major energy consuming proteins in the tail. A positive logarithmic transformed fold change value means upregulation in T3-treated group, and vice versa; *, p < 0.05. PDH, pyruvate dehydrogenase; CS, citrate synthase; IDH, isocitrate dehydrogenase; 2-OGDH, 2-oxoglutarate dehydrogenase; SCL, succinyl-CoA ligase; SDH, succinate dehydrogenase; MDH, malate dehydrogenase; ND, NADH dehydrogenase; MCK, muscle creatine kinase; UCP, uncoupling protein.
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CURRENT STATUS: Published
Version 2
Posted 21 Aug, 2020
Published
On 08 Oct, 2020
No community comments so far
Editorial decision: Accept
On 17 Sep, 2020
Review #1 received
Received 15 Sep, 2020
Reviewer #2 agreed
On 01 Sep, 2020
Review #2 received
Received 01 Sep, 2020
Reviewer #1 agreed
On 31 Aug, 2020
Reviewers invited
Invitations sent on 30 Aug, 2020
Editor assigned
On 17 Aug, 2020
Submission checks complete
On 16 Aug, 2020
Editor invited
On 16 Aug, 2020
No comments provided
Review #2 received
Received 20 Jul, 2020
Editorial decision: Major revision
On 20 Jul, 2020
Reviewer #2 agreed
On 14 Jul, 2020
Review #1 received
Received 26 Jun, 2020
Reviewer #1 agreed
On 11 Jun, 2020
Reviewers invited
Invitations sent on 29 May, 2020
Editor assigned
On 24 May, 2020
Submission checks complete
On 23 May, 2020
Editor invited
On 23 May, 2020
First submitted
On 22 May, 2020
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Subject Areas
Animal Physiology
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This preprint is under consideration at Frontiers in Zoology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Remarkable metabolic reorganization and altered metabolic requirements in frog metamorphic climax
Bin Wang
Chengdu Institute of Biology, CAS
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 2
Posted 21 Aug, 2020
Published
On 08 Oct, 2020
No community comments so far
Editorial decision: Accept
On 17 Sep, 2020
Review #1 received
Received 15 Sep, 2020
Reviewer #2 agreed
On 01 Sep, 2020
Review #2 received
Received 01 Sep, 2020
Reviewer #1 agreed
On 31 Aug, 2020
Reviewers invited
Invitations sent on 30 Aug, 2020
Editor assigned
On 17 Aug, 2020
Submission checks complete
On 16 Aug, 2020
Editor invited
On 16 Aug, 2020
No comments provided
Review #2 received
Received 20 Jul, 2020
Editorial decision: Major revision
On 20 Jul, 2020
Reviewer #2 agreed
On 14 Jul, 2020
Review #1 received
Received 26 Jun, 2020
Reviewer #1 agreed
On 11 Jun, 2020
Reviewers invited
Invitations sent on 29 May, 2020
Editor assigned
On 24 May, 2020
Submission checks complete
On 23 May, 2020
Editor invited
On 23 May, 2020
First submitted
On 22 May, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Animal Physiology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Frontiers in Zoology.
Background Metamorphic climax is the crucial stage of amphibian metamorphosis responsible for the morphological and functional changes necessary for transition to a terrestrial habitat. This developmental period is sensitive to environmental changes and pollution. Understanding its metabolic basis and requirements is significant for ecological and toxicological research. Rana omeimontis tadpoles are a useful model for investigating this stage as their liver is involved in both metabolic regulation and fat storage.
Results We used a combined approach of transcriptomics and metabolomics to study the metabolic reorganization during natural and T3-driven metamorphic climax in the liver and tail of Rana omeimontis tadpoles. The metabolic flux from the apoptotic tail replaced hepatic fat storage as metabolic fuel, resulting in increased hepatic amino acid and fat levels. In the liver, amino acid catabolism (transamination and urea cycle) was upregulated along with energy metabolism (TCA cycle and oxidative phosphorylation), while the carbohydrate and lipid catabolism (glycolysis, pentose phosphate pathway (PPP), and β-oxidation) decreased. The hepatic glycogen phosphorylation and gluconeogenesis were upregulated, and the carbohydrate flux was used for synthesis of glycan units (e.g., UDP-glucuronate). In the tail, glycolysis, β-oxidation, and transamination were all downregulated, accompanied by synchronous downregulation of energy production and consumption. Glycogenolysis was maintained in the tail, and the carbohydrate flux likely flowed into both PPP and the synthesis of glycan units (e.g., UDP-glucuronate and UDP-glucosamine). Fatty acid elongation and desaturation, as well as the synthesis of bioactive lipid (e.g., prostaglandins) were encouraged in the tail during metamorphic climax. Protein synthesis was downregulated in both the liver and tail. The significance of these metabolic adjustments and their potential regulation mechanism are discussed.
Conclusion The energic strategy and anabolic requirements during metamorphic climax were revealed at the molecular level. Amino acid made an increased contribution to energy metabolism during metamorphic climax. Carbohydrate anabolism was essential for the body construction of the froglets. The tail was critical in anabolism including synthesizing bioactive metabolites. These findings increase our understanding of amphibian metamorphosis and provide background information for ecological, evolutionary, conservation, and developmental studies of amphibians.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7