Key result
Sleeve gastrectomy improves glucose tolerance and reverses elevated glucocorticoid ratios in mice fed high-fat diets.
Why the study?
Most studies of glucocorticoid regulation after gastric surgery focused only on single tissues, circulating glucocorticoids, or HSD11B1 activity, leaving systemic multi-tissue glucocorticoid homeostasis incompletely understood.
Does sleeve gastrectomy improve glucocorticoid homeostasis and glucose tolerance in male mice on a high-fat diet?
Does sleeve gastrectomy improve glucocorticoid homeostasis and glucose tolerance in male mice on a high-fat diet?
Sleeve gastrectomy improves glucocorticoid homeostasis in mice by decreasing the circulating active/inactive glucocorticoid ratio, primarily through increased renal HSD11B2 activity.
SG may reduce tissue glucocorticoid activation after weight loss; leaves open whether HSD11B1 changes drive metabolic gains in humans.
Elevated intra-tissue levels of active glucocorticoids in patients with obesity are associated with insulin resistance, diabetes, impaired immune regulation, and other adverse effects. Sleeve gastrectomy (SG) induces significant weight loss and improves metabolic outcomes, including insulin resistance and hyperlipidemia. Among the enzymes controlling intracellular concentrations of active glucocorticoids, 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1, SDR26C1) has been extensively studied concerning obesity and post-gastric surgery interventions. However, most studies focused on either a single tissue, circulating glucocorticoid levels, or HSD11B1 activity. In this work, we showed that the circulating active/inactive glucocorticoid ratio (corticosterone (B)/11-dehydrocorticosterone (A)) negatively correlated with glucose tolerance. In male C57BL/6 mice, SG slightly reduced circulating mineralocorticoids and reversed the elevated B/A ratio seen in sham-operated mice after high-fat diet, while improving glucose tolerance. This change was likely due to increased renal 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2, SDR9C3) activity after SG. To provide a comprehensive overview of the systemic effects post-surgery, we evaluated enzymes involved in glucocorticoid homeostasis across tissues on mRNA, protein, and activity levels. Moreover, mRNA expression levels of transcription factors CCAAT enhancer-binding protein alpha ( Cebpa), Cebpb, and nuclear factor kappa b ( Nfκb (p50) ), as well as cytokines influencing Hsd11b1 and Hsd11b2 gene expression, were analyzed. The results emphasize stronger influence of renal HSD11B2 than hepatic HSD11B1 activity on the circulating B/A ratio, supported by intrarenal and intrahepatic B/A ratios. The improved glucocorticoid homeostasis following SG, indicated by decreased B/A ratios, proposes a lower risk of glucocorticoid-mediated adverse health effects, including chronic kidney disease, hypertension, and metabolic disturbances.
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Moser et al. (2026) studied Obesity / High-fat diet. Sleeve gastrectomy vs. Sham operation was evaluated on Circulating active/inactive glucocorticoid ratio (B/A ratio) and glucose tolerance. Sleeve gastrectomy in male mice reversed the elevated circulating active/inactive glucocorticoid ratio seen in sham-operated mice after a high-fat diet and improved glucose tolerance.
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