Chronic glucocorticoid treatment induces hepatic lipid accumulation and hyperinsulinaemia in part through actions on AgRP neurons

Abstract Glucocorticoids (GCs) are widely prescribed anti-inflammatory medicines, but their use can lead to metabolic side-effects. These may occur through direct actions of GCs on peripheral organs, but could also be mediated by the hypothalamic AgRP neurons, which can increase food intake and modi...

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Autores principales:	Erika Harno, Charlotte Sefton, Jonathan R. Wray, Tiffany-Jayne Allen, Alison Davies, Anthony P. Coll, Anne White
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/454fb846197a4d86a1ee9dc8b94bc978
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spelling	oai:doaj.org-article:454fb846197a4d86a1ee9dc8b94bc9782021-12-02T16:31:58ZChronic glucocorticoid treatment induces hepatic lipid accumulation and hyperinsulinaemia in part through actions on AgRP neurons10.1038/s41598-021-93378-32045-2322https://doaj.org/article/454fb846197a4d86a1ee9dc8b94bc9782021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93378-3https://doaj.org/toc/2045-2322Abstract Glucocorticoids (GCs) are widely prescribed anti-inflammatory medicines, but their use can lead to metabolic side-effects. These may occur through direct actions of GCs on peripheral organs, but could also be mediated by the hypothalamic AgRP neurons, which can increase food intake and modify peripheral metabolism. Therefore, the aim of this study was to examine the metabolic effects of chronic treatment with the GC corticosterone (Cort, 75 μg/ml in drinking water) in mice lacking the glucocorticoid receptor (GR) on AgRP neurons. Female AgRP-GR KO mice had delayed onset of Cort-induced hyperphagia. However, AgRP-GR KO had little impact on the increased body weight or adiposity seen with 3 weeks Cort treatment. Cort caused hepatic steatosis in control mice, but in Cort treated female AgRP-GR KO mice there was a 25% reduction in liver lipid content and lower plasma triglycerides. Additionally, Cort treatment led to hyperinsulinaemia, but compared to controls, Cort-treated AgRP-GR KO mice had both lower fasting insulin levels and lower insulin levels during a glucose tolerance test. In conclusion, these data indicate that GCs do act through AgRP neurons to contribute, at least in part, to the adverse metabolic consequences of chronic GC treatment.Erika HarnoCharlotte SeftonJonathan R. WrayTiffany-Jayne AllenAlison DaviesAnthony P. CollAnne WhiteNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Erika Harno Charlotte Sefton Jonathan R. Wray Tiffany-Jayne Allen Alison Davies Anthony P. Coll Anne White Chronic glucocorticoid treatment induces hepatic lipid accumulation and hyperinsulinaemia in part through actions on AgRP neurons
description	Abstract Glucocorticoids (GCs) are widely prescribed anti-inflammatory medicines, but their use can lead to metabolic side-effects. These may occur through direct actions of GCs on peripheral organs, but could also be mediated by the hypothalamic AgRP neurons, which can increase food intake and modify peripheral metabolism. Therefore, the aim of this study was to examine the metabolic effects of chronic treatment with the GC corticosterone (Cort, 75 μg/ml in drinking water) in mice lacking the glucocorticoid receptor (GR) on AgRP neurons. Female AgRP-GR KO mice had delayed onset of Cort-induced hyperphagia. However, AgRP-GR KO had little impact on the increased body weight or adiposity seen with 3 weeks Cort treatment. Cort caused hepatic steatosis in control mice, but in Cort treated female AgRP-GR KO mice there was a 25% reduction in liver lipid content and lower plasma triglycerides. Additionally, Cort treatment led to hyperinsulinaemia, but compared to controls, Cort-treated AgRP-GR KO mice had both lower fasting insulin levels and lower insulin levels during a glucose tolerance test. In conclusion, these data indicate that GCs do act through AgRP neurons to contribute, at least in part, to the adverse metabolic consequences of chronic GC treatment.
format	article
author	Erika Harno Charlotte Sefton Jonathan R. Wray Tiffany-Jayne Allen Alison Davies Anthony P. Coll Anne White
author_facet	Erika Harno Charlotte Sefton Jonathan R. Wray Tiffany-Jayne Allen Alison Davies Anthony P. Coll Anne White
author_sort	Erika Harno
title	Chronic glucocorticoid treatment induces hepatic lipid accumulation and hyperinsulinaemia in part through actions on AgRP neurons
title_short	Chronic glucocorticoid treatment induces hepatic lipid accumulation and hyperinsulinaemia in part through actions on AgRP neurons
title_full	Chronic glucocorticoid treatment induces hepatic lipid accumulation and hyperinsulinaemia in part through actions on AgRP neurons
title_fullStr	Chronic glucocorticoid treatment induces hepatic lipid accumulation and hyperinsulinaemia in part through actions on AgRP neurons
title_full_unstemmed	Chronic glucocorticoid treatment induces hepatic lipid accumulation and hyperinsulinaemia in part through actions on AgRP neurons
title_sort	chronic glucocorticoid treatment induces hepatic lipid accumulation and hyperinsulinaemia in part through actions on agrp neurons
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/454fb846197a4d86a1ee9dc8b94bc978
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Chronic glucocorticoid treatment induces hepatic lipid accumulation and hyperinsulinaemia in part through actions on AgRP neurons

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