Chronic glucocorticoid treatment induces hepatic lipid accumulation and hyperinsulinaemia in part through actions on AgRP neurons
AuthorsHarno, Erika; email: firstname.lastname@example.org
Wray, Jonathan R.
Coll, Anthony P.
White, Anne; email: email@example.com
MetadataShow full item record
AbstractAbstract: 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.
CitationScientific Reports, volume 11, issue 1, page 13776
PublisherNature Publishing Group UK
DescriptionFrom Springer Nature via Jisc Publications Router
History: received 2021-01-11, accepted 2021-06-04, registration 2021-06-24, pub-electronic 2021-07-02, online 2021-07-02, collection 2021-12
Publication status: Published
Funder: Mawer-Fitzgerald Endowment Fund
Funder: Medical Research Council; doi: http://dx.doi.org/10.13039/501100000265; Grant(s): MRC_MC_UU_12012.1