Immune-metabolic landscape and sleeve gastrectomy outcomes

Background: Sleeve gastrectomy (SG) is an effective treatment for severe obesity; however, postoperative metabolic responses vary considerably. Immune-metabolic dysregulation has been suggested as a key driver of this heterogeneity, yet the integrated effects of immune and metabolic status on surgical outcomes remain unclear. Methods: We conducted a retrospective single-center cohort study of adults undergoing SG between January 2021 and December 2023, with a 12-month postoperative follow-up. Comprehensive molecular analyses – including circulating cytokine profiling, plasma lipid analysis, and transcriptomic sequencing of subcutaneous and visceral adipose tissues – were performed. Participants were stratified into two groups based on preoperative immune-metabolic profiles defined by fasting insulin, C-reactive protein, and cytokine levels: a resilient profile (Group1) and a dysregulated profile (Group2). Results: Among 45 patients who underwent SG [mean (standard deviation, SD) age, 36.7 (11.0) years; 26 (57.8%) female], nine (20.0%) were classified as Group1 and 36 (80.0%) as Group2. At 12 months, mean (SD) total weight loss was 31.0 (6.8)% in Group1 vs. 25.9 (7.1)% in Group2 [difference, 5.1 (95% CI 1.9–8.3); P = .003]. Group1 showed greater improvement in insulin sensitivity and transient cytokine activation, whereas Group2 exhibited persistent inflammation, elevated long-chain lipid species, and transcriptomic enrichment in lipid storage, interleukin-17 signaling, and olfactory receptor pathways. Subclustering of Group2 revealed adipose-tissue-specific heterogeneity associated with divergent postoperative weight-loss trajectories, despite similar baseline profiles. Conclusions: Preoperative immune-metabolic status was associated with postoperative metabolic recovery after SG. Integrating immune-metabolic profiling with adipose transcriptomics may help identify patients more likely to achieve favorable outcomes and guide personalized interventions to enhance metabolic recovery.