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Endocrine Abstracts (2019) 63 S15.2 | DOI: 10.1530/endoabs.63.S15.2

ECE2019 Symposia European Young Endocrine Scientists (EYES) (6 abstracts)

Investigating glucocorticoid excess as mediators of bone marrow adiposity expansion during caloric restriction

Andrea Lovdel


UK.


Background: Bone marrow adipose tissue (BMAT) comprises >10% of total adipose mass in healthy humans and further increases during caloric restriction (CR). However, BMAT function during CR and other conditions remains poorly understood. Circulating glucocorticoids also increase during CR, and glucocorticoid therapy increases BMAT; thus, we hypothesise that glucocorticoid excess mediates BMAT expansion during CR. Many effects of endogenous glucocorticoid excess are mediated by 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1), which catalyses intracellular regeneration of active 11-hydroxy glucocorticoid from inert 11-keto forms.

Objectives: Determine 1) if CR increases glucocorticoid activity within adipose tissue and bones; and 2) if ablation of 11β-HSD1 blocks CR-induced BMAT expansion.

Methods: Male and female C57BL/6J mice lacking 11β-HSD1 (KO) or littermate controls were fed ad libitum (AL) or 70% of AL intake (CR) from 9–15 weeks of age. Each week, body mass and composition were measured and blood collected. Plasma corticosterone and 11-dehydrocorticosterone were measured by ELISA or liquid chromatography-tandem mass spectrometry. Bone loss and BMAT were measured by micro-computed tomography.

Results: 1) In control and KO mice, CR decreased body and lean mass. Body fat decreased in males only. CR increased circulating corticosterone levels in both sexes and genotypes. Circulating 11-dehydrocorticosterone concentration was significantly greater in AL and CR KO mice than in controls. 2) CR increased expression of the glucocorticoid target gene Fkbp5 in white adipose tissue and bone. CR-induced BMAT expansion occurred in females of both genotypes and in control males, but not in KO male mice. CR induced cortical bone loss in females only and this was unaffected by genotype.

Conclusions: CR increases glucocorticoid action within bones and induces cortical bone loss. Knockout of 11β-HSD1 prevents CR-induced BMAT expansion in male, but not female, mice. These findings highlight glucocorticoids as potential mediators of sexually-dimorphic BMAT formation during CR.

Volume 63

21st European Congress of Endocrinology

Lyon, France
18 May 2019 - 21 May 2019

European Society of Endocrinology 

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