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Conserved Metabolic Changes in Nondiabetic and Type 2 Diabetic Bariatric Surgery Patients: Global Metabolomic Pilot Study.

ABSTRACT: The goal of this study was to provide insight into the mechanism by which bariatric surgical procedures led to weight loss and improvement or resolution of diabetes. Global biochemical profiling was used to evaluate changes occurring in nondiabetic and type 2 diabetic (T2D) patients experiencing either less extreme sleeve gastrectomy or a full gastric bypass. We were able to identify changes in metabolism that were affected by standard preoperation liquid weight loss diet as well as by bariatric surgery itself. Preoperation weight-loss diet was associated with a strong lipid metabolism signature largely related to the consumption of adipose reserves for energy production. Glucose usage shift away from glycolytic pyruvate production toward pentose phosphate pathway, via glucose-6-phosphate, appeared to be shared across all patients regardless of T2D status or bariatric surgery procedure. Our results suggested that bariatric surgery might promote antioxidant defense and insulin sensitivity through both increased heme synthesis and HO activity or expression. Changes in histidine and its metabolites following surgery might be an indication of altered gut microbiome ecology or liver function. This initial study provided broad understanding of how metabolism changed globally in morbidly obese nondiabetic and T2D patients following weight-loss surgery.

SUBMITTER: Sarosiek K

PROVIDER: S-EPMC4736952 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.

Project description:BackgroundLipoprotein insulin resistance (LPIR) score is a composite biomarker representative of atherogenic dyslipidemia characteristic of early insulin resistance. It is elevated in obesity and may provide information not captured in glycosylated hemoglobin and homeostatic model assessment for insulin resistance. While bariatric surgery reduces diabetes incidence and resolves metabolic syndrome, the effect of bariatric surgery on LPIR is untested.ObjectivesWe sought to assess the effects of Roux-en-Y gastric bypass and sleeve gastrectomy on LPIR in nondiabetic women with obesity.SettingNonsmoking, nondiabetic, premenopausal Hispanic women, age ≥18 years, undergoing Roux-en-Y gastric bypass or sleeve gastrectomy at Bellevue Hospital were recruited for a prospective observational study.MethodsAnthropometric measures and blood sampling were performed preoperatively and at 6 and 12 months postoperatively. LPIR was measured by nuclear magnetic resonance spectroscopy.ResultsAmong 53 women (Roux-en-Y gastric bypass, n = 22; sleeve gastrectomy, n = 31), mean age was 32 ± 7 years and body mass index 44.1 ± 6.4 kg/m2. LPIR was reduced by 35 ± 4% and 46 ± 4% at 6 and 12 months after surgery, respectively, with no difference by procedure. Twenty-seven of 53 patients met International Diabetes Federation criteria for metabolic syndrome preoperatively and had concomitant higher homeostatic model assessment for insulin resistance, glycosylated hemoglobin, nonhigh-density lipoprotein-cholesterol and LPIR. Twenty-five of 27 patients experienced resolution of metabolic syndrome postoperatively. Concordantly, the preoperative differences in homeostatic model assessment for insulin resistance, glycosylated hemoglobin, and nonhigh-density lipoprotein-cholesterol between those with and without metabolic syndrome resolved at 6 and 12 months. In contrast, patients with metabolic syndrome preoperatively exhibited greater LPIR scores at 6 and 12 months postoperatively.ConclusionThis is the first study to demonstrate improvement in insulin resistance, as measured by LPIR, after bariatric surgery with no difference by procedure. This measure, but not traditional markers, was persistently higher in patients with a preoperative metabolic syndrome diagnosis, despite resolution of the condition.

Project description:Context:Altered cytokine levels and chronic low-grade inflammation contribute to metabolic dysfunction in obesity. The extent of cytokine changes and their impact on metabolic improvements after bariatric surgery have not been fully explored. Objective:To compare 76 circulating cytokines, chemokines, and secreted cytokine receptors in subjects with obesity and lean subjects and determine how these cytokines are altered by bariatric surgery. Design, Setting, and Participants:A total of 37 patients with obesity and 37 lean patients in a cross-sectional study at an academic medical center. We also investigated cytokine changes in 25 patients with obesity after bariatric surgery. Intervention:Bariatric surgery (Roux-en-Y gastric bypass and vertical sleeve gastrectomy). Main Outcome Measures:Quantification of 76 circulating cytokines, chemokines, and secreted cytokine receptors. Results:A total of 13 cytokines were significantly higher, and 4 lower, in patients with obesity relative to lean controls. Soluble vascular endothelial growth factor receptor 2 (sVEGFR2), soluble TNF receptor (sTNFR) 1, and sTNFR2 were positively correlated, and soluble receptor for advanced glycation end-products was inversely correlated, with weight and body mass index. sTNFR2 was positively correlated with fasting glucose, homeostatic model assessment of insulin resistance, and hemoglobin A1c. After bariatric surgery, adiponectin increased, and leptin decreased. Elevated sVEGFR2 levels in patients with obesity were decreased (P = 0.01), whereas reduced chemokine (C-X-C motif) ligand (CXCL) 12 levels in patients with obesity increased (P = 0.03) after surgery. Patients with higher soluble interleukin receptor (sIL) 1R2 and sIL-6R levels before surgery had greater weight loss after surgery (P < 0.05). Conclusions:We demonstrate that chemokine (C-C motif) ligand (CCL) 14, sVEGFR2, and platelet-derived growth factor BB are elevated in obesity, and CXCL12, CCL11, and CCL27 are lower in obesity. We found clinically concordant directionality between lean and patients with obesity and before vs after surgery for six cytokines, suggesting that bariatric surgery shifted the cytokine profiles of patients with obesity toward that of lean controls.

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Conserved Metabolic Changes in Nondiabetic and Type 2 Diabetic Bariatric Surgery Patients: Global Metabolomic Pilot Study.

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