Immunometabolic alterations induced by GBD surgery and adjunct pharmacotherapy with metformin, orlistat, statins, and ACE inhibitors.

backgroundObesity is a multifactorial disorder associated with chronic inflammation, metabolic dysfunction, and increased risk of comorbidities. This study evaluated the effects of Metformin, Orlistat, Statins, and ACE (Angiotensin-Converting Enzyme) inhibitors on inflammatory and metabolic pathways in obese individuals before and after gastric bypass and duodenal switch (GBD) surgery. METHODS AND

resultsEighty obese adults (BMI > 35 kg/m²) were divided into four groups based on pharmacological therapy. PBMCs were isolated pre- and post-treatment. Gene expression of IL-6, IL-10, IL-17, AMPK, GLUT4, TNF-α, TGF-β, IFN-γ, and key DEGs (TESK2, SLC8A1, UBXN1, ZEB2) was assessed via qPCR, with corresponding protein expression validated using Western blot. ELISA measured plasma cytokine levels, and flow cytometry was performed to evaluate Th1/Th2, Treg (CD4⁺CD25⁺FoxP3⁺), and Th17 (IL-17 A⁺) subsets. Metformin and Orlistat significantly upregulated AMPK and GLUT4, while GBD and Statin-treated groups showed notable reductions in IL-6, TNF-α, IFN-γ, and IL-17. Anti-inflammatory markers IL-10 and TGF-β increased post-surgery. TESK2 and UBXN1 were upregulated, whereas SLC8A1 and ZEB2 were downregulated at both mRNA and protein levels. Flow cytometry revealed a significant shift toward immune regulation, with decreased Th1 and Th17 cells and elevated Th2 and Tregs, particularly in the Metformin-Orlistat group post-GBD.

conclusionThese findings highlight the complementary immunometabolic effects of pharmacological and surgical interventions. Metformin and Orlistat promote metabolic improvement, while Statins and ACE inhibitors reduce inflammation. GBD surgery induces profound immunological and metabolic remodeling, supporting its role as a central strategy in comprehensive obesity management.