Non-canonical metabolic and molecular effects of calorie restriction are revealed by varying temporal conditions
Calorie restriction (CR) extends lifespan and healthspan in diverse species. Comparing ad libitum- and CR-fed mice is challenging due to their significantly different feeding patterns, with CR-fed mice consuming their daily meal in 2 h and then subjecting themselves to a prolonged daily fast. Here, we examine how ad libitum- and CR-fed mice respond to tests performed at various times and fasting durations and find that the effects of CR-insulin sensitivity, circulating metabolite levels, and mechanistic target of rapamycin 1 (mTORC1) activity-result from the specific temporal conditions chosen, with CR-induced improvements in insulin sensitivity observed only after a prolonged fast, and the observed differences in mTORC1 activity between ad libitum- and CR-fed mice dependent upon both fasting duration and the specific tissue examined. Our results demonstrate that much of our understanding of the effects of CR are related to when, relative to feeding, we choose to examine the mice.
Authors
- Heidi H. Pak (ORCID: https://orcid.org/0000-0002-3287-6133)
- Daniel Paredes (ORCID: https://orcid.org/0000-0002-9635-8001)
- Dudley W. Lamming (ORCID: https://orcid.org/0000-0002-0079-4467)
- Allison N. Grossberg (ORCID: https://orcid.org/0000-0001-5605-6423)
- Cara L. Green (ORCID: https://orcid.org/0000-0002-2293-9364)
- Reji Babygirija (ORCID: https://orcid.org/0000-0003-3719-5991)
- Mikaela Koller
- Monika Dzieciątkowska (ORCID: https://orcid.org/0000-0002-9947-2520)
- Rachel R. Sanderfoot
Institutions
- University of Denver (US)
- University of Wisconsin–Madison (US)
- Johns Hopkins University (US)
- William S. Middleton Memorial Veterans Hospital (US)
- University of Colorado Anschutz Medical Campus (US)
- University of Colorado Denver (US)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-08-20
- DOI
- https://doi.org/10.1016/j.celrep.2024.114663
- Citations
- 12
- Primary Topic
- Circadian rhythm and melatonin
- Type
- article
- Field-Weighted Citation Impact
- 3.29
Funders
- U.S. Department of Veterans Affairs
- Glenn Foundation for Medical Research
- University of Wisconsin-Madison
- Fondation pour la Recherche Médicale
- National Institutes of Health
- National Institute on Aging
- National Institute of Diabetes and Digestive and Kidney Diseases
- Division of Graduate Education