Endocrine Abstracts

Currently, most Type 2 Diabetes (T2D) treatments are targeted for the mitigation of the disease rather than remission. It has been previously demonstrated that T2D remission post-bariatric surgery in mice is independent of weight loss, indicating a metabolic mechanism. One avenue that remains largely unexplored is the role of cortisol, a hormone secreted from the adrenal cortex, dysregulation of which is linked to insulin resistance and obesity. The enzyme 11β-Hydroxysteroid Dehydrogenase 1 (11β-HSD1) is responsible for converting cortisone from the adrenal gland, into cortisol in the liver. We have previously shown that hepatic 11β-HSD1 expression significantly decreases post-Vertical Sleeve Gastrectomy (VSG), indicating the involvement of the adrenal gland in T2D remission. The aim of this study is to determine this metabolic involvement of the adrenal gland by analysing changes in 11β-HSD1 expression. Inflammation is a known highly predominant factor in T2D; therefore, it was hypothesised that inflammatory cytokines would have the largest affect in 11β-HSD1 expression. HepG2 human hepatoblastoma cells were treated with a variety of inflammatory cytokines and hormones (insulin, leptin, IL-6, and TNF-α) and 11β-HSD1 gene and protein expression were measured. Additionally, we performed VSG on high-fat diet fed C57BL/6J mice in order to investigate changes in adipokine and 11β-HSD1 expression levels in liver and adipose biopsies collected post-operatively. We found a statistically significant increase in 11β-HSD1 expression in cells treated with high concentrations of IL-6, mimicking the conditions observed in T2D. A difference in 11β-HSD1 expression was not observed with other treatments, further highlighting the significance of the correlation between IL-6 and 11β-HSD1 expression. To corroborate these results, IL-6 expression was significantly inhibited in the liver, and 11β-HSD1 was significantly inhibited in liver and adipose tissue post-VSG. The results of this study reveal a novel angle on bariatric surgery euglycemic effects, that includes cytokine-controlled cortisol function.