Type 2 Diabetes Metabolic Improvement After Roux-en-Y Gastric Bypass May Include A Compensatory Mechanism That Balances Fatty Acid β and ω Oxidation

Background: More than half patients underwent Roux-en-Y gastric bypass (RYGB) can experience type 2 diabetes (T2D) remission, but the systemic and gastrointestinal metabolic mechanisms of this improvement are still elusive.

Methods: Paired samples collected before and 3 months after RYGB from 28 women with obesity and T2D were analyzed by metabolomics with gas chromatography coupled to mass spectrometry. Samples include plasma (n = 56) and biopsies of gastric pouch (n = 18), gastric remnant (n = 10), duodenum (n = 16), jejunum (n = 18) and ileum (n = 18), collected by double-balloon enteroscopy.

Results: After RYGB, improvements in body composition, weight-related and glucose homeostasis parameters were observed. Plasma enriched metabolic pathways included arginine and proline metabolism, urea and tricarboxylic acid cycles, gluconeogenesis, malate-aspartate shuttle and carnitine synthesis. In gastrointestinal tissue, we observed alterations of ammonia recycling and carnitine synthesis in gastric pouch, phenylacetate metabolism and trehalose degradation in duodenum and jejunum, ketone bodies in jejunum, and lactose degradation in ileum. Intermediates molecules of the tricarboxylic acid cycle (TCA) were enriched, particularly in plasma, jejunum and ileum. Fluctuations of dicarboxylic acids (DCA) were relevant in several metabolomic tests and metabolite alterations included aminomalonate and fumaric, malic, oxalic and succinic acids. The product/substrate relationship between these molecules and its pathways may reflect a compensatory mechanism to balance metabolism.

Conclusions: RYGB was associated with systemic and GI metabolic reprogramming. DCA alterations links ω and β fatty acid oxidation to homeostatic mechanisms, including TCA cycle improvement. This article is protected by copyright. All rights reserved.

Keywords: bariatric surgery < research and diseases; metabolomics; obesity < research and diseases; succinate; type 2 diabetes.