Characterising 24-h skeletal muscle gene expression alongside metabolic & endocrine responses under diurnal conditions

Harry A Smith; Iain Templeman; Max Davis; Tommy Slater; David J Clayton; Ian Varley; Lewis J James; Benita Middleton; Jonathan D Johnston; Leonidas G Karagounis; Kostas Tsintzas; Dylan Thompson; Javier T Gonzalez; Jean-Philippe Walhin; James A Betts

doi:10.1210/clinem/dgae350

Characterising 24-h skeletal muscle gene expression alongside metabolic & endocrine responses under diurnal conditions

J Clin Endocrinol Metab. 2024 May 23:dgae350. doi: 10.1210/clinem/dgae350. Online ahead of print.

Authors

Affiliations

¹ Centre for Nutrition, Exercise and Metabolism, Department for Health, University of Bath, Bath, BA2 7AY, United Kingdom.
² Musculoskeletal Physiology Research Group, Sport, Health and Performance Enhancement Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, NG1 4FQ, United Kingdom.
³ National Centre for Sport and Exercise Medicine, School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough LE11 3TU, United Kingdom.
⁴ Section of Chronobiology, School of Biosciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH.
⁵ Institute of Social and Preventive Medicine, University of Bern, 3012 Bern, Switzerland.
⁶ Mary MacKillop Institute for Health Research (MMIHR), Australian Catholic University (ACU), Melbourne, Australia.
⁷ MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH.

PMID: 38779872
DOI: 10.1210/clinem/dgae350

Abstract

Context: Skeletal muscle plays a central role in the storage, synthesis, and breakdown of nutrients, yet little research has explored temporal responses of this human tissue, especially with concurrent measures of systemic biomarkers of metabolism.

Objective: To characterise temporal profiles in skeletal muscle expression of genes involved in carbohydrate metabolism, lipid metabolism, circadian clocks, and autophagy and descriptively relate them to systemic metabolites and hormones during a controlled laboratory protocol.

Methods: Ten healthy adults (9M/1F, mean ± SD: age: 30 ± 10 y; BMI: 24.1 ± 2.7 kg·m-2) rested in the laboratory for 37 hours with all data collected during the final 24 hours of this period (i.e., 0800-0800 h). Participants ingested hourly isocaloric liquid meal replacements alongside appetite assessments during waking before a sleep opportunity from 2200-0700 h. Blood samples were collected hourly for endocrine and metabolite analyses, with muscle biopsies occurring every 4 h from 1200 h to 0800 h the following day to quantify gene expression.

Results: Plasma insulin displayed diurnal rhythmicity peaking at 1804 h. Expression of skeletal muscle genes involved in carbohydrate metabolism (Name - Acrophase; GLUT4 - 1440 h; PPARGC1A -1613 h; HK2 - 1824 h) and lipid metabolism (FABP3 - 1237 h; PDK4 - 0530 h; CPT1B - 1258 h) displayed 24 h rhythmicity that reflected the temporal rhythm of insulin. Equally, circulating glucose (0019 h), NEFA (0456 h), glycerol (0432 h), triglyceride (2314 h), urea (0046 h), CTX (0507 h) and cortisol concentrations (2250 h) also all displayed diurnal rhythmicity.

Conclusion: Diurnal rhythms were present in human skeletal muscle gene expression as well systemic metabolites and hormones under controlled diurnal conditions. The temporal patterns of genes relating to carbohydrate and lipid metabolism alongside circulating insulin are consistent with diurnal rhythms being driven in part by the diurnal influence of cyclic feeding and fasting.

Keywords: Circadian rhythms; Diurnal; Gene expression; Glucose; Lipids; Skeletal muscle.