Roux-en-Y Gastric Bypass Versus Single Anastomosis Duodeno-Ileal Bypass With Sleeve Gastrectomy: Different Mechanisms, Similar Outcomes.

OBJECTIVE: We aimed to compare the molecular mechanisms and metabolic outcomes of Roux-en-Y gastric bypass (RYGB) and single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) using a preclinical model. METHODS: Otsuka Long-Evans Tokushima Fatty rats with diet-induced obesity underwent RYGB, SADI-S, or sham surgery. Metabolic parameters, including glucose tolerance, body weight, and 18F-fluorodeoxyglucose biodistribution, were assessed at 1- and 2-month postsurgery. The expression of Glucose transporter 1 (GLUT1) and glucose metabolism-related genes in intestinal segments was analyzed. RESULTS: Although RYGB and SADI-S yielded comparable improvements in glucose tolerance and body weight at 1 month postsurgery, they exerted their effects through distinct mechanisms. RYGB enhanced GLUT1-mediated glucose excretion in the common limb, whereas SADI-S upregulated the expression of the glycolytic genes Hk2, Fbp2, Aldob, and Ldha in the colon. Two months postsurgery, the observed metabolic improvements diminished despite sustained weight loss, which coincided with decreased expression of GLUT1 and glycolytic genes. CONCLUSIONS: RYGB and SADI-S achieve similar benefits through distinct glucose handling pathways; however, these effects decline over time. Our data do not support the superiority of SADI-S over RYGB, particularly given its higher complication rate, and instead highlight the need for strategies aimed at prolonging the therapeutic benefits of metabolic surgeries.