Zeitgebers of skeletal muscle and implications for metabolic health

Brendan Gabriel* (Corresponding Author), Juleen R. Zierath

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

11 Citations (Scopus)
14 Downloads (Pure)


Metabolic health is a crucial area of current research, and is an outcome of innate physiology, and interactions with the environment. Environmental cues, such as the Earth's day‐night rhythm, partly regulate diurnal hormones and metabolites. Circadian physiology consists of highly conserved biological processes over ∼24‐hour cycles, which are influenced by external cues (Zeitgebers – “time‐keepers”). Skeletal muscle has diurnal variations of a large magnitude, owing in part to the strong nature of physical activity throughout the day and other external Zeitgebers. The orchestration of whole‐body, and skeletal muscle metabolism is a complex, finely‐tuned process, and molecular diurnal variations are regulated by a transcription‐translation feedback loop controlled by the molecular clock, as well as non‐transcriptional metabolic processes. The mitochondrion may play an important role in regulating diurnal metabolites within skeletal muscle, given its central role in the regulation of NAD+/NADH, O2, reactive oxygen species and redox metabolism. These molecular pathways display diurnal variation and illustrate the complex orchestration of circadian metabolism in skeletal muscle. Probably the most robust Zeitgeber of skeletal muscle is exercise, which alters glucose metabolism and flux, in addition to a range of other diurnal metabolic pathways. Indeed, performing exercise at different times of the day may alter metabolism and health outcomes in some cohorts. The objective of this Symposium Review is to briefly cover the current literature, and to speculate regarding future areas of research. Thus, we postulate that metabolic health may be optimized by altering the timing of external cues such as diet and exercise.
Original languageEnglish
Pages (from-to)1027-1036
Number of pages10
JournalThe Journal of Physiology
Issue number5
Early online date31 May 2021
Publication statusE-pub ahead of print - 31 May 2021

Bibliographical note

Brendan M. Gabriel was supported by fellowships from the Novo Nordisk Foundation (NNF19OC0055072), and the Wenner-Gren Foundation, an Albert Renold Travel Fellowship from the European Foundation for the Study of Diabetes (EFSD), and a Young Investigator Research Award from EFSD/Lilly. J.R.Z. was supported from the Swedish Research Council (Vetenskapsrådet) (2015-00165), Novo Nordisk Foundation (NNF14OC0011493, NNF14OC0009941, NNF17OC0030088), Swedish Diabetes Foundation (DIA2018-357), the Swedish Research Council for Sport Science (P2019-0140), the Strategic Research Programme in Diabetes at Karolinska Institutet (2009-1068), Stockholm County Council (SLL20170159), and the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen (NNF18CC0034900).

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