Imperial College London
Alternate

DrIsabelleLeclerc

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 3354i.leclerc

 
 
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Location

 

323ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Akalestou:2022:10.3389/fendo.2022.1020576,
author = {Akalestou, E and Lopez-Noriega, L and Christakis, I and Hu, M and Miras, A and Leclerc, I and Rutter, G},
doi = {10.3389/fendo.2022.1020576},
journal = {Frontiers in Endocrinology},
pages = {1--16},
title = {Vertical Sleeve Gastrectomy normalizes circulating glucocorticoid levels and lowers glucocorticoid action tissue-selectively in mice},
url = {http://dx.doi.org/10.3389/fendo.2022.1020576},
volume = {13},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Objectives: Glucocorticoids produced by the adrenal cortex are essential for the maintenance of metabolic homeostasis.Glucocorticoid activation is catalysed by 11βhydroxysteroid dehydrogenase 1 (11βHSD1). Excess glucocorticoids are associatedwith insulin resistance and hyperglycaemia. A small number of studies have demonstrated effects on glucocorticoid metabolism ofbariatric surgery, a group of gastrointestinal procedures known to improve insulin sensitivity and secretion, which were assumedto result from weight loss. In this study, we hypothesize that a reduction in glucocorticoid action following bariatric surgerycontributes to the widely observed euglycemic effects of the treatment. Methods: Glucose and insulin tolerance tests wereperformed at ten weeks post operatively and circulating corticosterone was measured. Liver and adipose tissues were harvestedfrom fed mice and 11βHSD1 levels were measured by quantitative RTPCR or Western (immuno) blotting, respectively. 11βHSD1null mice (Hsd11b1-/-) were generated using CRISPR/ Cas9 genome editing. Wild type (WT) and littermate Hsd11b1-/- miceunderwent Vertical Sleeve Gastrectomy (VSG) or sham surgery. Results: WT VSG-treated mice displayed significantly improvedglucose tolerance versus sham controls, and this effect was observed in both regular chow- and HFD-fed animals. VSG lowered bodyweight in HFD but not regular chow-fed mice. Remarkably, VSG restored physiological corticosterone production in HFD mice andreduced 11βHSD1 expression in liver and adipose tissue postsurgery. Elimination of the 11βHSD1/Hsd11b1 gene mimicked theeffects of VSG on body weight and tolerance to 1g/kg glucose challenge. However, at 3 g/kg glucose, the impact of VSG on glucoseexcursion was indistinguishable between WT and Hsd11b1-/- mice, suggesting that the euglycemic effect of VSG was superior toHsd11b1 elimination. Conclusions: Bariatric surgery improves insulin sensitivity and reduces glucocorticoi
AU  - Akalestou,E
AU  - Lopez-Noriega,L
AU  - Christakis,I
AU  - Hu,M
AU  - Miras,A
AU  - Leclerc,I
AU  - Rutter,G
DO  - 10.3389/fendo.2022.1020576
EP  - 16
PY  - 2022///
SN  - 1664-2392
SP  - 1
TI  - Vertical Sleeve Gastrectomy normalizes circulating glucocorticoid levels and lowers glucocorticoid action tissue-selectively in mice
T2  - Frontiers in Endocrinology
UR  - http://dx.doi.org/10.3389/fendo.2022.1020576
UR  - https://www.frontiersin.org/articles/10.3389/fendo.2022.1020576/full
UR  - http://hdl.handle.net/10044/1/99596
VL  - 13
ER  -
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