Time-restricted feeding alters lipid and amino acid metabolite rhythmicity without perturbing clock gene expression.

Leonidas S Lundell, Evelyn B Parr, Brooke L Devlin, Lars R Ingerslev, Ali Altıntaş, Shogo Sato, Paolo Sassone-Corsi, Romain Barrès, Juleen R Zierath, John A Hawley

Journal: Nature communications 2020;11(1):4643

PMID: 32938935

Plain Language Summary

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There is growing evidence that less time spent in the fasted state may lead to chronic metabolic disorders such as diabetes and cardio vascular disease. Time-restricted feeding (TRF) is a practical way to control dietary intake by extending the time spent fasting and improves markers of metabolic health in both animals and humans. The inbuilt day/night cycle (circadian rhythm) is another important factor in metabolic health. 11 men with overweight/obesity took part in this randomised cross-over trial. In order to understand the mechanisms behind the beneficial effects of short-term TRF, a range of metabolites from skeletal muscle and blood serum were measured after 5 days of TRF (8 h per day) and then 5 days of extended feeding (EXF, 15 h per day). In this study, TRF changed the daily rhythm of lipid and amino acid metabolism, without modulating the core circadian rhythm in skeletal muscle. Long-term studies of TRF versus EXF in humans in real life settings, using more advanced molecular techniques are required to determine the exact mechanisms underlying the health-related benefits of TRF.

Abstract

Time-restricted feeding (TRF) improves metabolism independent of dietary macronutrient composition or energy restriction. To elucidate mechanisms underpinning the effects of short-term TRF, we investigated skeletal muscle and serum metabolic and transcriptomic profiles from 11 men with overweight/obesity after TRF (8 h day) and extended feeding (EXF, 15 h day) in a randomised cross-over design (trial registration: ACTRN12617000165381). Here we show that muscle core clock gene expression was similar after both interventions. TRF increases the amplitude of oscillating muscle transcripts, but not muscle or serum metabolites. In muscle, TRF induces rhythmicity of several amino acid transporter genes and metabolites. In serum, lipids are the largest class of periodic metabolites, while the majority of phase-shifted metabolites are amino acid related. In conclusion, short-term TRF in overweight men affects the rhythmicity of serum and muscle metabolites and regulates the rhythmicity of genes controlling amino acid transport, without perturbing core clock gene expression.

Address: Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Exercise and Nutrition Research Program, Mary MacKillop Institute for Health Research, Australian Catholic University, Fitzroy, VIC, 3000, Australia.; Center for Epigenetics and Metabolism, INSERM U1233, Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA, USA.; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. [email protected].; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. [email protected].; Exercise and Nutrition Research Program, Mary MacKillop Institute for Health Research, Australian Catholic University, Fitzroy, VIC, 3000, Australia. [email protected].

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