Vertical sleeve gastrectomy: Attenuating cortisol activation in mice and humans via pro-inflammatory cytokine reduction

Shiyi Liang; Wenya Wang; Suhaniya Samarasinghe; Antonio Riva; Alexander Miras; Elina Akalestou

doi:10.1530/endoabs.94.P207

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Endocrine Abstracts (2023) 94 P207 | DOI: 10.1530/endoabs.94.P207

SFEBES2023 Poster Presentations Metabolism, Obesity and Diabetes (70 abstracts)

Vertical sleeve gastrectomy: Attenuating cortisol activation in mice and humans via pro-inflammatory cytokine reduction

Shiyi Liang ¹ , Wenya Wang ¹ , Suhaniya Samarasinghe ¹ , Antonio Riva ^2,3 , Alexander Miras ^1,4 & Elina Akalestou ^1,5

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Author affiliations

¹Imperial College London, London, United Kingdom. ²The Roger Williams Institute of Hepatology, London, United Kingdom. ³King’s College London, London, United Kingdom. ⁴Ulster University, Belfast, United Kingdom. ⁵University of Leicester, Leicester, United Kingdom

Background: Cortisol is a hormone produced by the adrenal cortex and is essential for the maintenance of metabolic homeostasis. Cortisol activation is catalysed by 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) and excess cortisol is associated with insulin resistance and hyperglycaemia. Previous studies from our group have shown that Vertical Sleeve Gastrectomy, a gastrointestinal procedure known to improve insulin sensitivity, causes cortisol inhibition in mice, independent of weight loss. The aim of this study was to investigate the underpinning mechanisms of this observation in mice and humans.

Methods: High Fat Diet mice underwent Vertical Sleeve Gastrectomy (n=5) or sham (n=5) surgery. 11βHSD1 knockout mice were generated on a C57/BL6 background using CRISPR/Cas9. Cortisol, cytokines and 11βHSD1 levels were measured in intra and post-operative plasma and adipose tissue. Adipose tissue biopsies were obtained from patients undergoing Vertical Sleeve Gastrectomy at intra and 6 months post-operative timepoints. All biopsies were analysed using Magnetic Luminex Screening Assays and quantitative real-time PCR (qRT-PCR).

Results: Both HFD VSG and 11βHSD1-/- mice displayed significantly improved glucose and insulin tolerance (P<0.001). Cortisol secretion in plasma, and 11βHSD1 expression in adipose tissue, was significantly reduced in VSG mice, as previously shown. This was confirmed in liver and muscle biopsies. Cytokines interleukin-6 (IL-6), leptin and Transforming growth factor beta (TGF-β) were significantly inhibited in plasma and adipose tissue in both VSG and 11βHSD1-/- mice, while anti-inflammatory peptide FGF-21 concentration was increased. Expression of 11βHSD1, leptin and IL6 was also significantly reduced in human adipose tissue post- Vertical Sleeve Gastrectomy.

Conclusion: Vertical Sleeve Gastrectomy is shown to be inhibiting cortisol secretion and 11βHSD1 activity in both mice and humans, an effect that may represent an additional contribution to the health benefits of the surgery. The mechanism underlying this observation could involve a decrease in inflammatory cytokines, both circulating and at tissular level.