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Multiomics analyses reveal dynamic bioenergetic pathways and functional remodeling of the heart during intermittent fasting

Intermittent fasting (IF) has been shown to reduce cardiovascular risk factors in both animals and humans, and can protect the heart against ischemic injury in models of myocardial infarction. However, the underlying molecular mechanisms behind these effects remain unclear. To shed light on the mole...

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Autores principales: Arumugam, Thiruma V, Alli-Shaik, Asfa, Liehn, Elisa A, Selvaraji, Sharmelee, Poh, Luting, Rajeev, Vismitha, Cho, Yoonsuk, Cho, Yongeun, Kim, Jongho, Kim, Joonki, Swa, Hannah LF, Hao, David Tan Zhi, Rattanasopa, Chutima, Fann, David Yang-Wei, Mayan, David Castano, Ng, Gavin Yong-Quan, Baik, Sang-Ha, Mallilankaraman, Karthik, Gelderblom, Mathias, Drummond, Grant R, Sobey, Christopher G, Kennedy, Brian K, Singaraja, Roshni R, Mattson, Mark P, Jo, Dong-Gyu, Gunaratne, Jayantha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10538958/
https://www.ncbi.nlm.nih.gov/pubmed/37769126
http://dx.doi.org/10.7554/eLife.89214
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author Arumugam, Thiruma V
Alli-Shaik, Asfa
Liehn, Elisa A
Selvaraji, Sharmelee
Poh, Luting
Rajeev, Vismitha
Cho, Yoonsuk
Cho, Yongeun
Kim, Jongho
Kim, Joonki
Swa, Hannah LF
Hao, David Tan Zhi
Rattanasopa, Chutima
Fann, David Yang-Wei
Mayan, David Castano
Ng, Gavin Yong-Quan
Baik, Sang-Ha
Mallilankaraman, Karthik
Gelderblom, Mathias
Drummond, Grant R
Sobey, Christopher G
Kennedy, Brian K
Singaraja, Roshni R
Mattson, Mark P
Jo, Dong-Gyu
Gunaratne, Jayantha
author_facet Arumugam, Thiruma V
Alli-Shaik, Asfa
Liehn, Elisa A
Selvaraji, Sharmelee
Poh, Luting
Rajeev, Vismitha
Cho, Yoonsuk
Cho, Yongeun
Kim, Jongho
Kim, Joonki
Swa, Hannah LF
Hao, David Tan Zhi
Rattanasopa, Chutima
Fann, David Yang-Wei
Mayan, David Castano
Ng, Gavin Yong-Quan
Baik, Sang-Ha
Mallilankaraman, Karthik
Gelderblom, Mathias
Drummond, Grant R
Sobey, Christopher G
Kennedy, Brian K
Singaraja, Roshni R
Mattson, Mark P
Jo, Dong-Gyu
Gunaratne, Jayantha
author_sort Arumugam, Thiruma V
collection PubMed
description Intermittent fasting (IF) has been shown to reduce cardiovascular risk factors in both animals and humans, and can protect the heart against ischemic injury in models of myocardial infarction. However, the underlying molecular mechanisms behind these effects remain unclear. To shed light on the molecular and cellular adaptations of the heart to IF, we conducted comprehensive system-wide analyses of the proteome, phosphoproteome, and transcriptome, followed by functional analysis. Using advanced mass spectrometry, we profiled the proteome and phosphoproteome of heart tissues obtained from mice that were maintained on daily 12- or 16 hr fasting, every-other-day fasting, or ad libitum control feeding regimens for 6 months. We also performed RNA sequencing to evaluate whether the observed molecular responses to IF occur at the transcriptional or post-transcriptional levels. Our analyses revealed that IF significantly affected pathways that regulate cyclic GMP signaling, lipid and amino acid metabolism, cell adhesion, cell death, and inflammation. Furthermore, we found that the impact of IF on different metabolic processes varied depending on the length of the fasting regimen. Short IF regimens showed a higher correlation of pathway alteration, while longer IF regimens had an inverse correlation of metabolic processes such as fatty acid oxidation and immune processes. Additionally, functional echocardiographic analyses demonstrated that IF enhances stress-induced cardiac performance. Our systematic multi-omics study provides a molecular framework for understanding how IF impacts the heart’s function and its vulnerability to injury and disease.
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spelling pubmed-105389582023-09-29 Multiomics analyses reveal dynamic bioenergetic pathways and functional remodeling of the heart during intermittent fasting Arumugam, Thiruma V Alli-Shaik, Asfa Liehn, Elisa A Selvaraji, Sharmelee Poh, Luting Rajeev, Vismitha Cho, Yoonsuk Cho, Yongeun Kim, Jongho Kim, Joonki Swa, Hannah LF Hao, David Tan Zhi Rattanasopa, Chutima Fann, David Yang-Wei Mayan, David Castano Ng, Gavin Yong-Quan Baik, Sang-Ha Mallilankaraman, Karthik Gelderblom, Mathias Drummond, Grant R Sobey, Christopher G Kennedy, Brian K Singaraja, Roshni R Mattson, Mark P Jo, Dong-Gyu Gunaratne, Jayantha eLife Medicine Intermittent fasting (IF) has been shown to reduce cardiovascular risk factors in both animals and humans, and can protect the heart against ischemic injury in models of myocardial infarction. However, the underlying molecular mechanisms behind these effects remain unclear. To shed light on the molecular and cellular adaptations of the heart to IF, we conducted comprehensive system-wide analyses of the proteome, phosphoproteome, and transcriptome, followed by functional analysis. Using advanced mass spectrometry, we profiled the proteome and phosphoproteome of heart tissues obtained from mice that were maintained on daily 12- or 16 hr fasting, every-other-day fasting, or ad libitum control feeding regimens for 6 months. We also performed RNA sequencing to evaluate whether the observed molecular responses to IF occur at the transcriptional or post-transcriptional levels. Our analyses revealed that IF significantly affected pathways that regulate cyclic GMP signaling, lipid and amino acid metabolism, cell adhesion, cell death, and inflammation. Furthermore, we found that the impact of IF on different metabolic processes varied depending on the length of the fasting regimen. Short IF regimens showed a higher correlation of pathway alteration, while longer IF regimens had an inverse correlation of metabolic processes such as fatty acid oxidation and immune processes. Additionally, functional echocardiographic analyses demonstrated that IF enhances stress-induced cardiac performance. Our systematic multi-omics study provides a molecular framework for understanding how IF impacts the heart’s function and its vulnerability to injury and disease. eLife Sciences Publications, Ltd 2023-09-28 /pmc/articles/PMC10538958/ /pubmed/37769126 http://dx.doi.org/10.7554/eLife.89214 Text en © 2023, Arumugam, Alli-Shaik et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Medicine
Arumugam, Thiruma V
Alli-Shaik, Asfa
Liehn, Elisa A
Selvaraji, Sharmelee
Poh, Luting
Rajeev, Vismitha
Cho, Yoonsuk
Cho, Yongeun
Kim, Jongho
Kim, Joonki
Swa, Hannah LF
Hao, David Tan Zhi
Rattanasopa, Chutima
Fann, David Yang-Wei
Mayan, David Castano
Ng, Gavin Yong-Quan
Baik, Sang-Ha
Mallilankaraman, Karthik
Gelderblom, Mathias
Drummond, Grant R
Sobey, Christopher G
Kennedy, Brian K
Singaraja, Roshni R
Mattson, Mark P
Jo, Dong-Gyu
Gunaratne, Jayantha
Multiomics analyses reveal dynamic bioenergetic pathways and functional remodeling of the heart during intermittent fasting
title Multiomics analyses reveal dynamic bioenergetic pathways and functional remodeling of the heart during intermittent fasting
title_full Multiomics analyses reveal dynamic bioenergetic pathways and functional remodeling of the heart during intermittent fasting
title_fullStr Multiomics analyses reveal dynamic bioenergetic pathways and functional remodeling of the heart during intermittent fasting
title_full_unstemmed Multiomics analyses reveal dynamic bioenergetic pathways and functional remodeling of the heart during intermittent fasting
title_short Multiomics analyses reveal dynamic bioenergetic pathways and functional remodeling of the heart during intermittent fasting
title_sort multiomics analyses reveal dynamic bioenergetic pathways and functional remodeling of the heart during intermittent fasting
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10538958/
https://www.ncbi.nlm.nih.gov/pubmed/37769126
http://dx.doi.org/10.7554/eLife.89214
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