Abstract 13161: Longitudinal Profiling of Fasting Plasma Metabolome in Response to Weight-Loss Interventions in Patients With Morbid Obesity

Abstract

Background: The mechanisms underlying the favorable effects of Roux-en-Y gastric bypass (RYGB) over adjustable gastric banding (BAND) or non-surgical interventions on long-term metabolic outcomes remain largely unknown. Studies to date have largely been cross-sectional in nature and confounded by weight loss. Objective: Identify plasma metabolites associated with differential metabolic outcomes in response to different types of weight-loss interventions, independent of weight loss. Methods: We studied 75 patients with obesity (25 each in RYGB, BAND, or intensive medical intervention [IMI]) in the HeadsUp Study, a longitudinal study designed to evaluate the effectiveness of different weight-loss interventions. Using untargeted metabolomics (GC-TOF-MS), we repeatedly measured 364 metabolites (153 known) in fasting plasma samples collected at baseline and 1-year after intervention. Linear regression model was used to identify baseline metabolites predictive of changes in fasting plasma glucose (FPG) and HbA1c, adjusting for age, sex, BMI, FPG, or HbA1c at baseline and weight loss. Longitudinal associations were examined with linear mixed-effect models, adjusting for same covariates plus change in BMI and weight loss. Metabolites enrichment and network analyses were performed to identify related metabolic pathways. Results: We identified 41 baseline metabolites (18 known) significantly predictive of changes in FPG or HbA1c when comparing RYGB vs. IMI. Longitudinal changes in 37 metabolites (22 known) and 76 metabolites (32 known) were significantly associated with changes in FPG or HbA1c when comparing RYGB vs. IMI, and RYGB vs. BAND, respectively. The identified metabolites are enriched in pathways involved in aminoacyl-tRNA and branched chain amino acids (BCAAs) biosynthesis. Conclusion: Baseline plasma metabolites predict differential metabolic outcomes induced by different types of weight-loss interventions, with the effects being independent of weight loss. Our findings suggest that RYGB may exert its favorable metabolic effects via rewiring metabolism, and help identify patients who may obtain the greatest benefits from bariatric surgery.