Cargando…

Metabolomic Analysis of Carbohydrate and Amino Acid Changes Induced by Hypoxia in Naked Mole-Rat Brain and Liver

Hypoxia poses a major physiological challenge for mammals and has significant impacts on cellular and systemic metabolism. As with many other small rodents, naked mole-rats (NMRs; Heterocephalus glaber), who are among the most hypoxia-tolerant mammals, respond to hypoxia by supressing energy demand...

Descripción completa

Detalles Bibliográficos
Autores principales: Cheng, Hang, Qin, Yiming (Amy), Dhillon, Rashpal, Dowell, James, Denu, John M., Pamenter, Matthew E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779284/
https://www.ncbi.nlm.nih.gov/pubmed/35050178
http://dx.doi.org/10.3390/metabo12010056
_version_ 1784637537663320064
author Cheng, Hang
Qin, Yiming (Amy)
Dhillon, Rashpal
Dowell, James
Denu, John M.
Pamenter, Matthew E.
author_facet Cheng, Hang
Qin, Yiming (Amy)
Dhillon, Rashpal
Dowell, James
Denu, John M.
Pamenter, Matthew E.
author_sort Cheng, Hang
collection PubMed
description Hypoxia poses a major physiological challenge for mammals and has significant impacts on cellular and systemic metabolism. As with many other small rodents, naked mole-rats (NMRs; Heterocephalus glaber), who are among the most hypoxia-tolerant mammals, respond to hypoxia by supressing energy demand (i.e., through a reduction in metabolic rate mediated by a variety of cell- and tissue-level strategies), and altering metabolic fuel use to rely primarily on carbohydrates. However, little is known regarding specific metabolite changes that underlie these responses. We hypothesized that NMR tissues utilize multiple strategies in responding to acute hypoxia, including the modulation of signalling pathways to reduce anabolism and reprogram carbohydrate metabolism. To address this question, we evaluated changes of 64 metabolites in NMR brain and liver following in vivo hypoxia exposure (7% O(2), 4 h). We also examined changes in matched tissues from similarly treated hypoxia-intolerant mice. We report that, following exposure to in vivo hypoxia: (1) phenylalanine, tyrosine and tryptophan anabolism are supressed both in NMR brain and liver; (2) carbohydrate metabolism is reprogramed in NMR brain and liver, but in a divergent manner; (3) redox state is significantly altered in NMR brain; and (4) the AMP/ATP ratio is elevated in liver. Overall, our results suggest that hypoxia induces significant metabolic remodelling in NMR brain and liver via alterations of multiple metabolic pathways.
format Online
Article
Text
id pubmed-8779284
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-87792842022-01-22 Metabolomic Analysis of Carbohydrate and Amino Acid Changes Induced by Hypoxia in Naked Mole-Rat Brain and Liver Cheng, Hang Qin, Yiming (Amy) Dhillon, Rashpal Dowell, James Denu, John M. Pamenter, Matthew E. Metabolites Article Hypoxia poses a major physiological challenge for mammals and has significant impacts on cellular and systemic metabolism. As with many other small rodents, naked mole-rats (NMRs; Heterocephalus glaber), who are among the most hypoxia-tolerant mammals, respond to hypoxia by supressing energy demand (i.e., through a reduction in metabolic rate mediated by a variety of cell- and tissue-level strategies), and altering metabolic fuel use to rely primarily on carbohydrates. However, little is known regarding specific metabolite changes that underlie these responses. We hypothesized that NMR tissues utilize multiple strategies in responding to acute hypoxia, including the modulation of signalling pathways to reduce anabolism and reprogram carbohydrate metabolism. To address this question, we evaluated changes of 64 metabolites in NMR brain and liver following in vivo hypoxia exposure (7% O(2), 4 h). We also examined changes in matched tissues from similarly treated hypoxia-intolerant mice. We report that, following exposure to in vivo hypoxia: (1) phenylalanine, tyrosine and tryptophan anabolism are supressed both in NMR brain and liver; (2) carbohydrate metabolism is reprogramed in NMR brain and liver, but in a divergent manner; (3) redox state is significantly altered in NMR brain; and (4) the AMP/ATP ratio is elevated in liver. Overall, our results suggest that hypoxia induces significant metabolic remodelling in NMR brain and liver via alterations of multiple metabolic pathways. MDPI 2022-01-10 /pmc/articles/PMC8779284/ /pubmed/35050178 http://dx.doi.org/10.3390/metabo12010056 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cheng, Hang
Qin, Yiming (Amy)
Dhillon, Rashpal
Dowell, James
Denu, John M.
Pamenter, Matthew E.
Metabolomic Analysis of Carbohydrate and Amino Acid Changes Induced by Hypoxia in Naked Mole-Rat Brain and Liver
title Metabolomic Analysis of Carbohydrate and Amino Acid Changes Induced by Hypoxia in Naked Mole-Rat Brain and Liver
title_full Metabolomic Analysis of Carbohydrate and Amino Acid Changes Induced by Hypoxia in Naked Mole-Rat Brain and Liver
title_fullStr Metabolomic Analysis of Carbohydrate and Amino Acid Changes Induced by Hypoxia in Naked Mole-Rat Brain and Liver
title_full_unstemmed Metabolomic Analysis of Carbohydrate and Amino Acid Changes Induced by Hypoxia in Naked Mole-Rat Brain and Liver
title_short Metabolomic Analysis of Carbohydrate and Amino Acid Changes Induced by Hypoxia in Naked Mole-Rat Brain and Liver
title_sort metabolomic analysis of carbohydrate and amino acid changes induced by hypoxia in naked mole-rat brain and liver
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779284/
https://www.ncbi.nlm.nih.gov/pubmed/35050178
http://dx.doi.org/10.3390/metabo12010056
work_keys_str_mv AT chenghang metabolomicanalysisofcarbohydrateandaminoacidchangesinducedbyhypoxiainnakedmoleratbrainandliver
AT qinyimingamy metabolomicanalysisofcarbohydrateandaminoacidchangesinducedbyhypoxiainnakedmoleratbrainandliver
AT dhillonrashpal metabolomicanalysisofcarbohydrateandaminoacidchangesinducedbyhypoxiainnakedmoleratbrainandliver
AT dowelljames metabolomicanalysisofcarbohydrateandaminoacidchangesinducedbyhypoxiainnakedmoleratbrainandliver
AT denujohnm metabolomicanalysisofcarbohydrateandaminoacidchangesinducedbyhypoxiainnakedmoleratbrainandliver
AT pamentermatthewe metabolomicanalysisofcarbohydrateandaminoacidchangesinducedbyhypoxiainnakedmoleratbrainandliver