Roux-en-Y Gastric Bypass Surgery Induces Early Plasma Metabolomic and Lipidomic Alterations in Humans Associated with Diabetes Remission

PLoS One. 2015 May 6;10(5):e0126401. doi: 10.1371/journal.pone.0126401. eCollection 2015.

Abstract

Roux-en-Y gastric bypass (RYGB) is an effective method to attain sustained weight loss and diabetes remission. We aimed to elucidate early changes in the plasma metabolome and lipidome after RYGB. Plasma samples from 16 insulin-resistant morbidly obese subjects, of whom 14 had diabetes, were subjected to global metabolomics and lipidomics analysis at pre-surgery and 4 and 42 days after RYGB. Metabolites and lipid species were compared between time points and between subjects who were in remission and not in remission from diabetes 2 years after surgery. We found that the variables that were most discriminatory between time points were decanoic acid and octanoic acid, which were elevated 42 days after surgery, and sphingomyelins (18:1/21:0 and 18:1/23:3), which were at their lowest level 42 days after surgery. Insulin levels were lower at 4 and 42 days after surgery compared with pre-surgery levels. At 4 days after surgery, insulin levels correlated positively with metabolites of branched chain and aromatic amino acid metabolism and negatively with triglycerides with long-chain fatty acids. Of the 14 subjects with diabetes prior to surgery, 7 were in remission 2 years after surgery. The subjects in remission displayed higher pre-surgery levels of tricarboxylic acid cycle intermediates and triglycerides with long-chain fatty acids compared with subjects not in remission. Thus, metabolic alterations are induced soon after surgery and subjects with diabetes remission differ in the metabolic profiles at pre- and early post-surgery time points compared to patients not in remission.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / metabolism*
  • Caprylates / blood
  • Decanoic Acids / blood
  • Diabetes Mellitus / pathology
  • Diabetes Mellitus / surgery
  • Fatty Acids / metabolism*
  • Female
  • Gastric Bypass*
  • Humans
  • Insulin Resistance / physiology
  • Male
  • Metabolome
  • Metabolomics
  • Middle Aged
  • Obesity, Morbid / metabolism*
  • Obesity, Morbid / surgery
  • Sphingomyelins / blood
  • Triglycerides / metabolism*
  • Weight Loss

Substances

  • Amino Acids
  • Caprylates
  • Decanoic Acids
  • Fatty Acids
  • Sphingomyelins
  • Triglycerides
  • octanoic acid

Grant support

This work was supported by the Human Frontier of Science Program (RGY64/2008), Swedish Research Council, Swedish Diabetes Foundation, Swedish Foundation for Strategic Research, Swedish Heart Lung Foundation, the EU-funded project ETHERPATHS (FP7-KBBE-222639, www.etherpaths.org), Torsten Söderberg’s, Ragnar Söderberg’s, and NovoNordisk Foundations, and LUA-ALF grants from Västra Götalandsregionen. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.