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An Untargeted Metabolomics Approach to Characterize Short-Term and Long-Term Metabolic Changes after Bariatric Surgery.

ABSTRACT: Bariatric surgery is currently one of the most effective treatments for obesity and leads to significant weight reduction, improved cardiovascular risk factors and overall survival in treated patients. To date, most studies focused on short-term effects of bariatric surgery on the metabolic profile and found high variation in the individual responses to surgery. The aim of this study was to identify relevant metabolic changes not only shortly after bariatric surgery (Roux-en-Y gastric bypass) but also up to one year after the intervention by using untargeted metabolomics. 132 serum samples taken from 44 patients before surgery, after hospital discharge (1-3 weeks after surgery) and at a 1-year follow-up during a prospective study (NCT01271062) performed at two study centers (Austria and Switzerland). The samples included 24 patients with type 2 diabetes at baseline, thereof 9 with diabetes remission after one year. The samples were analyzed by using liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS, HILIC-QExactive). Raw data was processed with XCMS and drift-corrected through quantile regression based on quality controls. 177 relevant metabolic features were selected through Random Forests and univariate testing and 36 metabolites were identified. Identified metabolites included trimethylamine-N-oxide, alanine, phenylalanine and indoxyl-sulfate which are known markers for cardiovascular risk. In addition we found a significant decrease in alanine after one year in the group of patients with diabetes remission relative to non-remission. Our analysis highlights the importance of assessing multiple points in time in subjects undergoing bariatric surgery to enable the identification of biomarkers for treatment response, cardiovascular benefit and diabetes remission. Key-findings include different trend pattern over time for various metabolites and demonstrated that short term changes should not necessarily be used to identify important long term effects of bariatric surgery.

SUBMITTER: Narath SH

PROVIDER: S-EPMC5008721 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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An Untargeted Metabolomics Approach to Characterize Short-Term and Long-Term Metabolic Changes after Bariatric Surgery.

Narath Sophie H SH Mautner Selma I SI Svehlikova Eva E Schultes Bernd B Pieber Thomas R TR Sinner Frank M FM Gander Edgar E Libiseller Gunnar G Schimek Michael G MG Sourij Harald H Magnes Christoph C

PloS one 20160901 9

Bariatric surgery is currently one of the most effective treatments for obesity and leads to significant weight reduction, improved cardiovascular risk factors and overall survival in treated patients. To date, most studies focused on short-term effects of bariatric surgery on the metabolic profile and found high variation in the individual responses to surgery. The aim of this study was to identify relevant metabolic changes not only shortly after bariatric surgery (Roux-en-Y gastric bypass) bu ...[more]

PMID: 27584017

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Project description:Bariatric surgery is currently one of the most effective treatments for obesity and leads to significant weight reduction, improved cardiovascular risk factors and overall survival in treated patients. To date, most studies focused on short-term effects of bariatric surgery on the metabolic profile and found high variation in the individual responses to surgery. The aim of this study was to identify relevant metabolic changes not only shortly after bariatric surgery (Roux-en-Y gastric bypass) but also up to one year after the intervention by using untargeted metabolomics. 132 serum samples taken from 44 patients before surgery, after hospital discharge (1–3 weeks after surgery) and at a 1-year follow-up during a prospective study (NCT01271062) performed at two study centers (Austria and Switzerland). The samples included 24 patients with type 2 diabetes at baseline, thereof 9 with diabetes remission after one year. The samples were analyzed by using liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS, HILIC-QExactive). Raw data was processed with XCMS and drift-corrected through quantile regression based on quality controls. 177 relevant metabolic features were selected through Random Forests and univariate testing and 36 metabolites were identified. Identified metabolites included trimethylamine-N-oxide, alanine, phenylalanine and indoxyl-sulfate which are known markers for cardiovascular risk. In addition we found a significant decrease in alanine after one year in the group of patients with diabetes remission relative to non-remission. Our analysis highlights the importance of assessing multiple points in time in subjects undergoing bariatric surgery to enable the identification of biomarkers for treatment response, cardiovascular benefit and diabetes remission. Key-findings include different trend pattern over time for various metabolites and demonstrated that short term changes should not necessarily be used to identify important long term effects of bariatric surgery.

Project description:ContextThe mechanisms mediating the short- and long-term improvements in glucose homeostasis following bariatric/metabolic surgery remain incompletely understood.ObjectiveTo investigate whether a reduction in adipose tissue inflammation plays a role in the metabolic improvements seen after bariatric/metabolic surgery, both in the short-term and longer-term.DesignFasting blood and subcutaneous abdominal adipose tissue were obtained before (n=14), at one month (n=9), and 6-12months (n=14) after bariatric/metabolic surgery from individuals with obesity who were not on insulin or anti-diabetes medication. Adipose tissue inflammation was assessed by a combination of whole-tissue gene expression and flow cytometry-based quantification of tissue leukocytes.ResultsOne month after surgery, body weight was reduced by 13.5±4.4kg (p<0.001), with improvements in glucose tolerance reflected by a decrease in area-under-the-curve (AUC) glucose in 3-h oral glucose tolerance tests (-105±98mmol/L * min; p=0.009) and enhanced pancreatic β-cell function (insulinogenic index: +0.8±0.9pmol/mmol; p=0.032), but no change in estimated insulin sensitivity (Matsuda insulin sensitivity index [ISI]; p=0.720). Furthermore, although biomarkers of systemic inflammation and pro-inflammatory gene expression in adipose tissue remained unchanged, the number of neutrophils increased in adipose tissue 15-20 fold (p<0.001), with less substantial increases in other leukocyte populations. By the 6-12month follow-up visit, body weight was reduced by 34.8±10.8kg (p<0.001) relative to baseline, and glucose tolerance was further improved (AUC glucose -276±229; p<0.001) along with estimated insulin sensitivity (Matsuda ISI: +4.6±3.2; p<0.001). In addition, improvements in systemic inflammation were reflected by reductions in circulating C-reactive protein (CRP; -2.0±5.3mg/dL; p=0.002), and increased serum adiponectin (+1358±1406pg/mL; p=0.003). However, leukocyte infiltration of adipose tissue remained elevated relative to baseline, with pro-inflammatory cytokine mRNA expression unchanged, while adiponectin mRNA expression trended downward (p=0.069).ConclusionBoth the short- and longer-term metabolic improvements following bariatric/metabolic surgery occur without significant reductions in measures of adipose tissue inflammation, as assessed by measuring the expression of genes encoding key mediators of inflammation and by flow cytometric immunophenotyping and quantification of adipose tissue leukocytes.

Project description:BackgroundAdvances in untargeted metabolomic technologies have great potential for insight into adverse metabolic effects underlying exposure to environmental chemicals. However, important challenges need to be addressed, including how biological response corresponds to the environmental chemical burden in different target tissues.AimWe performed a pilot study using state-of-the-art ultra-high-resolution mass spectrometry (UHRMS) to characterize the burden of lipophilic persistent organic pollutants (POPs) in metabolic tissues and associated alterations in the plasma metabolome.MethodsWe studied 11 adolescents with severe obesity at the time of bariatric surgery. We measured 18 POPs that can act as endocrine and metabolic disruptors (i.e. 2 dioxins, 11 organochlorine compounds [OCs] and 5 polybrominated diphenyl ethers [PBDEs]) in visceral and subcutaneous abdominal adipose tissue (vAT and sAT), and liver samples using gas chromatography with UHRMS. Biological pathways were evaluated by measuring the plasma metabolome using high-resolution metabolomics. Network and pathway enrichment analysis assessed correlations between the tissue-specific burden of three frequently detected POPs (i.e. p,p'-dichlorodiphenyldichloroethene [DDE], hexachlorobenzene [HCB] and PBDE-47) and plasma metabolic pathways.ResultsConcentrations of 4 OCs and 3 PBDEs were quantifiable in at least one metabolic tissue for > 80% of participants. All POPs had the highest median concentrations in adipose tissue, especially sAT, except for PBDE-154, which had comparable average concentrations across all tissues. Pathway analysis showed high correlations between tissue-specific POPs and metabolic alterations in pathways of amino acid metabolism, lipid and fatty acid metabolism, and carbohydrate metabolism.ConclusionsMost of the measured POPs appear to accumulate preferentially in adipose tissue compared to liver. Findings of plasma metabolic pathways potentially associated with tissue-specific POPs concentrations merit further investigation in larger populations.

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An Untargeted Metabolomics Approach to Characterize Short-Term and Long-Term Metabolic Changes after Bariatric Surgery.

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An Untargeted Metabolomics Approach to Characterize Short-Term and Long-Term Metabolic Changes after Bariatric Surgery.

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