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Gut Adaptation After Gastric Bypass in Humans Reveals Metabolically Significant Shift in Fuel Metabolism

ABSTRACT: Objective: Roux-en-Y gastric bypass surgery (RYGB) is among the most effective therapies for obesity and type 2 diabetes (T2D), and intestinal adaptation is a proposed mechanism for these effects. We hypothesized that intestinal adaptation precedes and relates to metabolic improvement in humans after RYGB. Methods: This was a prospective, longitudinal first-in-human study of gene expression (GE) in Roux limb (RL) collected surgically/endoscopically from 19 patients with and without diabetes. GE was determined by microarray across 6 postoperative months, including at an early postoperative (1 month  15 days) timepoint. Results: RL GE demonstrated tissue remodeling and metabolic reprogramming, including increased glucose and amino acid utilization. RL GE signatures were established early, before maximal clinical response, and persisted. Distinct GE fingerprints predicted concurrent and future improvements in HbA1c and in weight. Human RL exhibits GE changes characterized by anabolic growth and shift in metabolic substrate utilization. Paradoxically, anabolic growth in RL appears to contribute to the catabolic state elicited by RYGB. Conclusions: These data support a role for a direct effect of intestinal energy metabolism to contribute to the beneficial clinical effects of RYGB, suggesting that related pathways might be potential targets of therapeutic interest for patients with obesity with or without T2D.

ORGANISM(S): Homo sapiens

PROVIDER: GSE281144 | GEO | 2024/11/09

REPOSITORIES: GEO

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