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

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

eLife

10.7554/eLife.89214.2

http://dx.doi.org/10.7554/elife.89214.2

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

28 September 2023

Arumugam, T. V., Alli-Shaik, A., Liehn, E. A., Selvaraji, S., Poh, L., Rajeev, V., Cho, Y., Cho, Y., Kim, J., Kim, J., Swa, H. L., Hao, D. T. Z., Rattanasopa, C., Fann, D. Y.-W., Mayan, D. C., Ng, G. Y.-Q., Baik, S.-H., Mallilankaraman, K., Gelderblom, M., … Gunaratne, J. (2023). Multiomics analyses reveal dynamic bioenergetic pathways and functional remodeling of the heart during intermittent fasting. ELife, 12. CLOCKSS. https://doi.org/10.7554/elife.89214.2

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.

Attribution 4.0 International (CC BY 4.0)

This research is supported by core funding from: Singapore and Agency for Science, Technology and Research, Singapore
Grant Reference no. : NA

This research / project is supported by the National Medical Research Council - Cooperative Basic Research Grant
Grant Reference no. : NMRC-CBRG-0102/2016

This research / project is supported by the National Medical Research Council - Open Fund - Individual Research Grant
Grant Reference no. : NMRC/OFIRG/0036/2017

This work was supported by ODPRT, National University of Singapore and Start up fund from La Trobe University, Melbourne, Australia.

https://oar.a-star.edu.sg/communities-collections/articles/20306

2050-084X

Institute of Molecular and Cell Biology

https://doi.org/10.7554/eLife.89214.2