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Metabolomic and transcriptomic profiling of adult mice and larval zebrafish leptin mutants reveal a common pattern of changes in metabolites and signaling pathways

BACKGROUND: Leptin plays a critical role in the regulation of metabolic homeostasis. However, the molecular mechanism and cross talks between leptin and metabolic pathways leading to metabolic homeostasis across different species are not clear. This study aims to explore the effects of leptin in mic...

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Autores principales: Ding, Yi, Haks, Mariëlle C., Forn-Cuní, Gabriel, He, Junling, Nowik, Natalia, Harms, Amy C., Hankemeier, Thomas, Eeza, Muhamed N. H., Matysik, Jörg, Alia, A., Spaink, Herman P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265131/
https://www.ncbi.nlm.nih.gov/pubmed/34233759
http://dx.doi.org/10.1186/s13578-021-00642-0
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author Ding, Yi
Haks, Mariëlle C.
Forn-Cuní, Gabriel
He, Junling
Nowik, Natalia
Harms, Amy C.
Hankemeier, Thomas
Eeza, Muhamed N. H.
Matysik, Jörg
Alia, A.
Spaink, Herman P.
author_facet Ding, Yi
Haks, Mariëlle C.
Forn-Cuní, Gabriel
He, Junling
Nowik, Natalia
Harms, Amy C.
Hankemeier, Thomas
Eeza, Muhamed N. H.
Matysik, Jörg
Alia, A.
Spaink, Herman P.
author_sort Ding, Yi
collection PubMed
description BACKGROUND: Leptin plays a critical role in the regulation of metabolic homeostasis. However, the molecular mechanism and cross talks between leptin and metabolic pathways leading to metabolic homeostasis across different species are not clear. This study aims to explore the effects of leptin in mice and zebrafish larvae by integration of metabolomics and transcriptomics. Different metabolomic approaches including mass spectrometry, nuclear magnetic resonance (NMR) and high-resolution magic-angle-spinning NMR spectrometry were used to investigate the metabolic changes caused by leptin deficiency in mutant ob/ob adult mice and lepb(−/−) zebrafish larvae. For transcriptome studies, deep RNA sequencing was used. RESULTS: Thirteen metabolites were identified as common biomarkers discriminating ob/ob mice and lepb(−/−) zebrafish larvae from their respective wild type controls: alanine, citrulline, ethanolamine, glutamine, glycine, histidine, isoleucine, leucine, methionine, phenylalanine, putrescine, serine and threonine. Moreover, we also observed that glucose and lipid levels were increased in lepb(−/−) zebrafish larvae compared to the lepb(+/+) group. Deep sequencing showed that many genes involved in proteolysis and arachidonic acid metabolism were dysregulated in ob/ob mice heads and lepb mutant zebrafish larvae compared to their wild type controls, respectively. CONCLUSIONS: Leptin deficiency leads to highly similar metabolic alterations in metabolites in both mice and zebrafish larvae. These metabolic changes show similar features as observed during progression of tuberculosis in human patients, mice and zebrafish larvae. In addition, by studying the transcriptome, we found similar changes in gene regulation related to proteolysis and arachidonic acid metabolism in these two different in vivo models. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13578-021-00642-0.
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spelling pubmed-82651312021-07-08 Metabolomic and transcriptomic profiling of adult mice and larval zebrafish leptin mutants reveal a common pattern of changes in metabolites and signaling pathways Ding, Yi Haks, Mariëlle C. Forn-Cuní, Gabriel He, Junling Nowik, Natalia Harms, Amy C. Hankemeier, Thomas Eeza, Muhamed N. H. Matysik, Jörg Alia, A. Spaink, Herman P. Cell Biosci Research BACKGROUND: Leptin plays a critical role in the regulation of metabolic homeostasis. However, the molecular mechanism and cross talks between leptin and metabolic pathways leading to metabolic homeostasis across different species are not clear. This study aims to explore the effects of leptin in mice and zebrafish larvae by integration of metabolomics and transcriptomics. Different metabolomic approaches including mass spectrometry, nuclear magnetic resonance (NMR) and high-resolution magic-angle-spinning NMR spectrometry were used to investigate the metabolic changes caused by leptin deficiency in mutant ob/ob adult mice and lepb(−/−) zebrafish larvae. For transcriptome studies, deep RNA sequencing was used. RESULTS: Thirteen metabolites were identified as common biomarkers discriminating ob/ob mice and lepb(−/−) zebrafish larvae from their respective wild type controls: alanine, citrulline, ethanolamine, glutamine, glycine, histidine, isoleucine, leucine, methionine, phenylalanine, putrescine, serine and threonine. Moreover, we also observed that glucose and lipid levels were increased in lepb(−/−) zebrafish larvae compared to the lepb(+/+) group. Deep sequencing showed that many genes involved in proteolysis and arachidonic acid metabolism were dysregulated in ob/ob mice heads and lepb mutant zebrafish larvae compared to their wild type controls, respectively. CONCLUSIONS: Leptin deficiency leads to highly similar metabolic alterations in metabolites in both mice and zebrafish larvae. These metabolic changes show similar features as observed during progression of tuberculosis in human patients, mice and zebrafish larvae. In addition, by studying the transcriptome, we found similar changes in gene regulation related to proteolysis and arachidonic acid metabolism in these two different in vivo models. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13578-021-00642-0. BioMed Central 2021-07-07 /pmc/articles/PMC8265131/ /pubmed/34233759 http://dx.doi.org/10.1186/s13578-021-00642-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Ding, Yi
Haks, Mariëlle C.
Forn-Cuní, Gabriel
He, Junling
Nowik, Natalia
Harms, Amy C.
Hankemeier, Thomas
Eeza, Muhamed N. H.
Matysik, Jörg
Alia, A.
Spaink, Herman P.
Metabolomic and transcriptomic profiling of adult mice and larval zebrafish leptin mutants reveal a common pattern of changes in metabolites and signaling pathways
title Metabolomic and transcriptomic profiling of adult mice and larval zebrafish leptin mutants reveal a common pattern of changes in metabolites and signaling pathways
title_full Metabolomic and transcriptomic profiling of adult mice and larval zebrafish leptin mutants reveal a common pattern of changes in metabolites and signaling pathways
title_fullStr Metabolomic and transcriptomic profiling of adult mice and larval zebrafish leptin mutants reveal a common pattern of changes in metabolites and signaling pathways
title_full_unstemmed Metabolomic and transcriptomic profiling of adult mice and larval zebrafish leptin mutants reveal a common pattern of changes in metabolites and signaling pathways
title_short Metabolomic and transcriptomic profiling of adult mice and larval zebrafish leptin mutants reveal a common pattern of changes in metabolites and signaling pathways
title_sort metabolomic and transcriptomic profiling of adult mice and larval zebrafish leptin mutants reveal a common pattern of changes in metabolites and signaling pathways
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265131/
https://www.ncbi.nlm.nih.gov/pubmed/34233759
http://dx.doi.org/10.1186/s13578-021-00642-0
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