Metabolomics Study of Roux-en-Y Gastric Bypass Surgery (RYGB) to Treat Type 2 Diabetes Patients Based on Ultraperformance Liquid Chromatography–Mass Spectrometry

Luo, Ping; Yu, Haoyong; Zhao, Xinjie; Bao, Yuqian; Hong, Christopher S.; Pin, Zhang; Tu, Ya; Yin, Peiyuan; Gao, Peng; Li, Wei; Zhuang, Zhengping; Jia, Weiping; Xu, Guowang

doi:10.1021/acs.jproteome.6b00022

Cited by 51 publications

(57 citation statements)

References 59 publications

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“…Even though serum NEFA level did not change significantly at 2 weeks, significant reduction was observed at 6 months post‐RYGB. Similarly, Luo et al observed a significant reduction of NEFAs by 6 months and 1 year post RYGB in subjects who had remission of diabetes . NEFAs are chronically elevated in persons with obesity and type 2 diabetes due to increased lipolysis in the adipose tissue with insulin resistance and mitochondrial dysfunction, corresponding with an inability to switch from fat oxidation to carbohydrate oxidation .…”

Section: Discussionmentioning

confidence: 88%

“…Similarly, Luo et al observed a significant reduction of NEFAs by 6 months and 1 year post RYGB in subjects who had remission of diabetes. 9 NEFAs are chronically elevated in persons with obesity and type 2 diabetes due to increased lipolysis in the adipose tissue with insulin resistance and mitochondrial dysfunction, corresponding with an inability to switch from fat oxidation to carbohydrate oxidation. 26,27 In addition, high levels of NEFAs induce and/or aggravate insulin resistance mainly in the liver and muscle, creating a vicious cycle.…”

Section: Resultsmentioning

confidence: 99%

“…4 Past studies have also investigated changes in metabolism that occur due to bariatric surgery using metabolomics. 2,7 These include investigations of differences between bariatric surgery types, 8 serial changes in metabolism post-surgery at different time points, [9][10][11][12][13] comparison of bariatric surgery vs dietary restrictions, 14,15 prediction of outcomes of bariatric surgery, 16 and post-prandial metabolic changes post-bariatric surgery. 15,17 Post-bariatric surgery follow-up studies have reported various changes in some metabolites in serum/ plasma 10,11 or urine.…”

Section: Introductionmentioning

confidence: 99%

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Roux‐en‐Y gastric bypass surgery alters serum metabolites and fatty acids in patients with morbid obesity

Wijayatunga

Sams

Dawson

et al. 2018

Diabetes Metabolism Res

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AimBariatric surgery induces significant weight loss, increases insulin sensitivity, and reduces mortality, but the underlying mechanisms are not clear. It was hypothesized that Roux‐en‐Y gastric bypass (RYGB) surgery improves metabolic profile along with weight loss. The objective of this pilot study was to evaluate changes in serum metabolites and fatty acids (FA) at 2 weeks and 6 months after RYGB.Materials and MethodsSerum samples were collected pre‐surgery, at 2 weeks and 6 months post‐surgery from 20 patients undergoing RYGB surgery. Serum non‐esterified free FA (NEFA) were measured. Serum metabolites and FA were measured using nuclear magnetic resonance spectroscopy and improved direct fatty acid methyl ester synthesis and the gas chromatography/mass spectrometry method, respectively, in subjects who completed follow‐up at 6 months (n = 8).ResultsMean (standard deviation) percent total weight loss was 6.70% (1.7) and 24.91% (6.63) at 2 weeks (n = 15) and 6 months (n = 8) post‐surgery, respectively. NEFA were significantly reduced at 6 months post‐surgery (P = 0.001, n = 8). Serum branched chain amino acids, 2‐aminobutyrate, butyrate, 2‐hydroxybutyrate, 3‐hydroxybutyrate, acetone, 2‐methylglutarate, and 2‐oxoisocaproate were significantly reduced, while serum alanine, glycine, pyruvate, and taurine were significantly elevated at 6 months post‐surgery compared with pre‐surgery (n = 8, P < 0.05). Also, serum FA C10:0, C13:0, C14:0, C15:0, and C18:0 increased significantly (n = 8, P < 0.05) by 6 months post‐surgery.ConclusionsChanges in serum metabolites and FA at 6 months post‐RYGB surgery in this pilot study with limited number of participants are suggestive of metabolic improvement; larger studies are warranted for confirmation.

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Section: Discussionmentioning

confidence: 88%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Roux‐en‐Y gastric bypass surgery alters serum metabolites and fatty acids in patients with morbid obesity

Wijayatunga

Sams

Dawson

et al. 2018

Diabetes Metabolism Res

View full text Add to dashboard Cite

show abstract

“…Only a limited number of longitudinal observational studies, using a metabolomics approach, have investigated serum biomarkers that could predict RYGB‐induced remission of diabetes. Luo et al (32) reported a global, untargeted metabolomics strategy that used human serum samples collected before surgery and 6 and 12 mo after RYGB. Results showed that baseline levels of tryptophan, bilirubin, and indoxyl sulfate best predicted the suitability and efficacy of RYGB for patients with T2DM.…”

Section: Discussionmentioning

confidence: 99%

Serum stearic acid/palmitic acid ratio as a potential predictor of diabetes remission after Roux‐en‐Y gastric bypass in obesity

Zhao

et al. 2016

FASEB j.

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Endogenous fatty acid metabolism that results in elongation and desaturation lipid products is thought to play a role in the development of type 2 diabetes mellitus (T2DM). In this study, we evaluated the potential of estimated elongase and desaturase activities for use as predictive markers for T2DM remission after Roux-en-Y gastric bypass (RYGB). The results of a targeted metabolomics approach from 2 independent studies were used to calculate 24 serum FA concentration ratios (product/precursor). Gene expression data from an open public data set was also analyzed. In a longitudinal study of 38 obese diabetic patients with RYGB, we found higher baseline stearic acid/palmitic acid (S/P) ratio. This ratio reflects an -encoded elongase enzyme activity that has been found to be associated with greater possibility for diabetes remission after RYGB [odds ratio, 2.16 (95% CI 1.10-4.26)], after adjustment for age, gender, body mass index, diabetes duration, glycosylated hemoglobin A1c, and fasting C-peptide. Our results were validated by examination of postsurgical gene expression in morbidly obese patients. The association of S/P with the metabolic status of obese individuals was further validated in a cross-sectional cohort of 381 participants. In summary, higher baseline S/P was associated with greater probability of diabetes remission after RYGB and may serve as a diagnostic marker in preoperative patient assessment. - Zhao, L., Ni, Y., Yu, H., Zhang, P., Zhao, A., Bao, Y., Liu, J., Chen, T., Xie, G., Panee, J., Chen, W., Rajani, C., Wei, R., Su, M., Jia, W., Jia, W. Serum stearic acid/palmitic acid ratio as a potential predictor of diabetes remission after Roux-en-Y gastric bypass in obesity.

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“…In this light, several clinical studies have been conducted on bariatric surgery patients to collect tissue, urine, and serum samples and experimentally quantify various biomolecules post-surgery using proteomics 4,5 and metabolomics 6,7 approaches. However, access to intestinal, liver, and visceral fat tissue post-surgery is highly invasive and therefore information on the metabolic dynamics in these specific organs has largely been elusive based on human clinical studies.…”

Section: Introductionmentioning

confidence: 99%

Multi-omic network-based interrogation of rat liver metabolism following gastric bypass surgery featuring SWATH proteomics

et al. 2017

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Morbidly obese patients often elect for Roux-en-Y gastric bypass (RYGB), a form of bariatric surgery that triggers a remarkable 30% reduction in excess body weight and reversal of insulin resistance for those who are type II diabetic. A more complete understanding of the underlying molecular mechanisms that drive the complex metabolic reprogramming post-RYGB could lead to innovative non-invasive therapeutics that mimic the beneficial effects of the surgery, namely weight loss, achievement of glycemic control, or reversal of non-alcoholic steatohepatitis (NASH). To facilitate these discoveries, we hereby demonstrate the first multi-omic interrogation of a rodent RYGB model to reveal tissue-specific pathway modules implicated in the control of body weight regulation and energy homeostasis. In this study, we focus on and evaluate liver metabolism three months following RYGB in rats using both SWATH proteomics, a burgeoning label free approach using high resolution mass spectrometry to quantify protein levels in biological samples, as well as MRM metabolomics. The SWATH analysis enabled the quantification of 1378 proteins in liver tissue extracts, of which we report the significant down-regulation of Thrsp and Acot13 in RYGB as putative targets of lipid metabolism for weight loss. Furthermore, we develop a computational graph-based metabolic network module detection algorithm for the discovery of non-canonical pathways, or sub-networks, enriched with significantly elevated or depleted metabolites and proteins in RYGB-treated rat livers. The analysis revealed a network connection between the depleted protein Baat and the depleted metabolite taurine, corroborating the clinical observation that taurine-conjugated bile acid levels are perturbed post-RYGB.

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Metabolomics Study of Roux-en-Y Gastric Bypass Surgery (RYGB) to Treat Type 2 Diabetes Patients Based on Ultraperformance Liquid Chromatography–Mass Spectrometry

Cited by 51 publications

References 59 publications

Roux‐en‐Y gastric bypass surgery alters serum metabolites and fatty acids in patients with morbid obesity

Roux‐en‐Y gastric bypass surgery alters serum metabolites and fatty acids in patients with morbid obesity

Serum stearic acid/palmitic acid ratio as a potential predictor of diabetes remission after Roux‐en‐Y gastric bypass in obesity

Multi-omic network-based interrogation of rat liver metabolism following gastric bypass surgery featuring SWATH proteomics

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