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

Smith, H.A., Templeman, I., Davis, M., Slater, T. ORCID: 0000-0003-2764-3148, Clayton, D.J. ORCID: 0000-0001-5481-0891, Varley, I. ORCID: 0000-0002-3607-8921, James, L.J., Middleton, B., Johnston, J.D., Karagounis, L.G., Tsintzas, K., Thompson, D., Gonzalez, J.T., Walhin, J.-P. and Betts, J.A., 2024. Characterising 24-h skeletal muscle gene expression alongside metabolic & endocrine responses under diurnal conditions. The Journal of Clinical Endocrinology and Metabolism. ISSN 0021-972X

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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.

Item Type:	Journal article
Publication Title:	The Journal of Clinical Endocrinology and Metabolism
Creators:	Smith, H.A., Templeman, I., Davis, M., Slater, T., Clayton, D.J., Varley, I., James, L.J., Middleton, B., Johnston, J.D., Karagounis, L.G., Tsintzas, K., Thompson, D., Gonzalez, J.T., Walhin, J.-P. and Betts, J.A.
Publisher:	Oxford University Press
Date:	23 May 2024
ISSN:	0021-972X
Identifiers:	Number Type 10.1210/clinem/dgae350 DOI 1897672 Other
Divisions:	Schools > School of Science and Technology
Record created by:	Melissa Cornwell
Date Added:	29 May 2024 08:59
Last Modified:	29 May 2024 08:59
URI:	https://irep.ntu.ac.uk/id/eprint/51480

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