Glucocorticoid excess alters metabolic rate and substrate utilisation via 11β-HSD1

Heaselgrave, SR, Heising, S, Morgan, SA, Carthwright, DM, Sagmeister, M, Hardy, RS, Doig, CL ORCID: https://orcid.org/0000-0001-9694-4230, Morton, NM ORCID: https://orcid.org/0000-0001-8218-8462, Tsintzas, K and Lavery, GG ORCID: https://orcid.org/0000-0001-5794-748X, 2024. Glucocorticoid excess alters metabolic rate and substrate utilisation via 11β-HSD1. Journal of Endocrinology, 263 (2): e240205. ISSN 0022-0795

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Abstract

Systemic glucocorticoid excess causes several adverse metabolic conditions, most notably Cushing’s syndrome. These effects are amplified by the intracellular enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Here, we determined the less well-characterised effects of glucocorticoid excess, and the contribution of 11β-HSD1 amplification on metabolic rate in mice. Male and female C57BL/6J (wild type, WT) and 11β-HSD1 knockout (11β-HSD1 KO) mice were treated with high-dose corticosterone or a vehicle control for 3 weeks. Indirect calorimetry was conducted during the final week of treatment, with or without fasting, to determine the impact on metabolic rate. We found that corticosterone treatment elevated metabolic rate and promoted carbohydrate utilisation primarily in female WT mice, with effects more pronounced during the light phase. Corticosterone treatment also resulted in greater fat accumulation in female WT mice. Corticosterone induced hyperphagia was identified as a likely causal factor altering the respiratory exchange ratio (RER) but not energy expenditure (EE). Male and female 11β-HSD1 KO mice were protected against these effects. We identify novel metabolic consequences of sustained glucocorticoid excess, identify a key mechanism of hyperphagia, and demonstrate that 11β-HSD1 is required to manifest the full metabolic derangement.

Item Type:	Journal article
Publication Title:	Journal of Endocrinology
Creators:	Heaselgrave, S.R., Heising, S., Morgan, S.A., Carthwright, D.M., Sagmeister, M., Hardy, R.S., Doig, C.L., Morton, N.M., Tsintzas, K. and Lavery, G.G.
Publisher:	BioScientifica Ltd.
Date:	November 2024
Volume:	263
Number:	2
ISSN:	0022-0795
Identifiers:	Number Type 10.1530/JOE-24-0205 DOI 2465204 Other
Rights:	© 2024 the author(s). This work is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)
Divisions:	Schools > School of Science and Technology
Record created by:	Laura Borcherds
Date Added:	08 Jul 2025 16:06
Last Modified:	08 Jul 2025 16:06
URI:	https://irep.ntu.ac.uk/id/eprint/53906

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