Non-canonical metabolic and molecular effects of calorie restriction are revealed by varying temporal conditions
Heidi H. Pak,
Allison N. Grossberg,
Rachel R. Sanderfoot,
Reji Babygirija,
Cara L. Green,
Mikaela Koller,
Monika Dzieciatkowska,
Daniel A. Paredes,
Dudley W. Lamming
Affiliations
Heidi H. Pak
Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI, USA; Interdepartmental Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, USA
Allison N. Grossberg
Knoebel Institute for Healthy Aging, University of Denver, Denver, CO, USA; Department of Biological Sciences, University of Denver, Denver, CO, USA
Rachel R. Sanderfoot
Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI, USA
Reji Babygirija
Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI, USA; Graduate Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, WI, USA
Cara L. Green
Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI, USA
Mikaela Koller
Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI, USA
Monika Dzieciatkowska
Department of Biochemistry & Molecular Genetics, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, CO, USA
Daniel A. Paredes
Department of Biological Sciences, University of Denver, Denver, CO, USA; Department of Electrical and Computer Engineering, University of Denver, Denver, CO, USA; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA
Dudley W. Lamming
Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI, USA; Interdepartmental Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, USA; Graduate Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, WI, USA; Corresponding author
Summary: 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.
