Gastric resection and restriction yield distinct neuroendocrine and metabolic outcomes in obese mice

Whether the metabolic benefits of sleeve gastrectomy arise from gastric restriction alone or also depend on tissue resection remains unclear. We compared sleeve gastrectomy (SG) with a surgical sleeve gastroplasty (GP) model that restricts the stomach without removing tissue. Diet-induced obese male C57BL mice were randomized to SG, GP, or sham surgery and evaluated over six weeks for energy balance, glucose regulation, hepatic lipid accumulation, circulating hormones and branched chain amino acids (BCAAs), and hypothalamic neuropeptide expression. SG and GP produced comparable weight loss of 12 and 11 percent, respectively, without significant differences in energy expenditure. However, the procedures differed in the timing of reduced food intake, and only SG produced smaller, more frequent meals. Both procedures improved glucose handling, with greater improvement after SG. SG also selectively reduced hepatic triglyceride content and circulating BCAAs. Hypothalamic POMC expression decreased after both procedures, whereas NPY and AgRP expression decreased only after SG. SG further produced a distinct hormonal profile, including higher fasting GLP1 and PYY, lower ghrelin, and greater glucose-stimulated increases in several gut and pancreatic hormones. Thus, comparable short-term weight loss after gastric resection and non-resection restriction was accompanied by distinct metabolic and neuroendocrine responses. These findings support a contribution of gastric resection beyond restriction alone and identify candidate gut-brain and metabolic pathways for developing less invasive interventions that reproduce the broader benefits of sleeve gastrectomy.