Back to Search Start Over

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

Authors :
Thiruma V Arumugam
Asfa Alli-Shaik
Elisa A Liehn
Sharmelee Selvaraji
Luting Poh
Vismitha Rajeev
Yoonsuk Cho
Yongeun Cho
Jongho Kim
Joonki Kim
Hannah LF Swa
David Tan Zhi Hao
Chutima Rattanasopa
David Yang-Wei Fann
David Castano Mayan
Gavin Yong-Quan Ng
Sang-Ha Baik
Karthik Mallilankaraman
Mathias Gelderblom
Grant R Drummond
Christopher G Sobey
Brian K Kennedy
Roshni R Singaraja
Mark P Mattson
Dong-Gyu Jo
Jayantha Gunaratne
Source :
eLife, Vol 12 (2023)
Publication Year :
2023
Publisher :
eLife Sciences Publications Ltd, 2023.

Abstract

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.

Details

Language :
English
ISSN :
2050084X
Volume :
12
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.77c3c141082e4538bda530d5762d0666
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.89214