Vertical Sleeve Gastrectomy inhibits 11βHSD1 and subsequently reduces IL6 secretion in Mice and Humans: A Shared Anti-Inflammatory Mechanism

Background Vertical sleeve gastrectomy (VSG) improves glycaemic control in type 2 diabetes (T2D) through mechanisms that extend beyond weight loss. The interaction between glucocorticoid metabolism and inflammation in this context remains unclear. Methods We investigated the role of 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) in mediating the metabolic effects of VSG in humans and mice. Subcutaneous adipose tissue biopsies were collected before and 6 months after VSG. Parallel studies were conducted in lean and high-fat diet-fed mice undergoing VSG or sham surgery, alongside 11βHSD1 knockout models. Glucose tolerance and expression of 11βHSD1 and interleukin-6 (IL6) were assessed. Results VSG reduced 11βHSD1 and IL6 expression in human adipose tissue and improved insulin resistance. In lean mice, VSG reduced adipose Hsd11b1 and Il6 expression and altered glucose handling in the absence of detectable changes in total body weight. 11βHSD1 knockout mice exhibited improved glucose tolerance despite increased body weight, partially recapitulating the VSG phenotype. Both interventions reduced circulating and tissue IL6 levels. Conclusions These findings identify an association between reduced 11βHSD1, inflammatory signalling and metabolic adaptations following VSG, and support further investigation of 11βHSD1 as a potential contributor to the metabolic effects of surgery.