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Time course metabolome of Roux-en-Y gastric bypass confirms correlation between leptin, body weight and the microbiome.

ABSTRACT: Roux-en-Y gastric bypass (RYGB) is an effective way to lose weight and reverse type 2 diabetes. We profiled the metabolome of 18 obese patients (nine euglycemic and nine diabetics) that underwent RYGB surgery and seven lean subjects. Plasma samples from the obese patients were collected before the surgery and one week and three months after the surgery. We analyzed the metabolome in association to five hormones (Adiponectin, Insulin, Ghrelin, Leptin, and Resistin), four peptide hormones (GIP, Glucagon, GLP1, and PYY), and two cytokines (IL-6 and TNF). PCA showed samples cluster by surgery time and many microbially driven metabolites (indoles in particular) correlated with the three months after the surgery. Network analysis of metabolites revealed a connection between carbohydrate (mannosamine and glucosamine) and glyoxylate and confirms glyoxylate association to diabetes. Only leptin and IL-6 had a significant association with the measured metabolites. Leptin decreased immediately after RYGB (before significant weight loss), whereas IL-6 showed no consistent response to RYGB. Moreover, leptin associated with tryptophan in support of the possible role of leptin in the regulation of serotonin synthesis pathways in the gut. These results suggest a potential link between gastric leptin and microbial-derived metabolites in the context of obesity and diabetes.

SUBMITTER: Seridi L

PROVIDER: S-EPMC5979615 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Time course metabolome of Roux-en-Y gastric bypass confirms correlation between leptin, body weight and the microbiome.

Seridi Loqmane L Leo Gregory C GC Dohm G Lynis GL Pories Walter J WJ Lenhard James J

PloS one 20180531 5

Roux-en-Y gastric bypass (RYGB) is an effective way to lose weight and reverse type 2 diabetes. We profiled the metabolome of 18 obese patients (nine euglycemic and nine diabetics) that underwent RYGB surgery and seven lean subjects. Plasma samples from the obese patients were collected before the surgery and one week and three months after the surgery. We analyzed the metabolome in association to five hormones (Adiponectin, Insulin, Ghrelin, Leptin, and Resistin), four peptide hormones (GIP, Gl ...[more]

PMID: 29851973

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Project description:BackgroundThe mechanisms of weight loss and metabolic improvements following bariatric surgery in skeletal muscle are not well known; however, epigenetic modifications are likely to contribute. The aim of our study was to investigate skeletal muscle DNA methylation after weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Muscle biopsies were obtained basally from seven insulin-resistant obese (BMI > 40 kg/m2) female subjects (45.1 ± 3.6 years) pre- and 3-month post-surgery with euglycemic hyperinsulinemic clamps to assess insulin sensitivity. Four lean (BMI < 25 kg/m2) females (38.5 ± 5.8 years) served as controls. We performed reduced representation bisulfite sequencing next generation methylation on DNA isolated from the vastus lateralis muscle biopsies.ResultsGlobal methylation was significantly higher in the pre- (32.97 ± 0.02%) and post-surgery (33.31 ± 0.02%) compared to the lean (30.46 ± 0.02%), P < 0.05. MethylSig analysis identified 117 differentially methylated cytosines (DMCs) that were significantly altered in the post- versus pre-surgery (Benjamini-Hochberg q < 0.05). In addition, 2978 DMCs were significantly altered in the pre-surgery obese versus the lean controls (Benjamini-Hochberg q < 0.05). For the post-surgery obese versus the lean controls, 2885 DMCs were altered (Benjamini-Hochberg q < 0.05). Seven post-surgery obese DMCs were normalized to levels similar to those observed in lean controls. Of these, 5 were within intergenic regions (chr11.68,968,018, chr16.73,100,688, chr5.174,115,531, chr5.1,831,958 and chr9.98,547,011) and the remaining two DMCs chr17.45,330,989 and chr14.105,353,824 were within in the integrin beta 3 (ITGB3) promoter and KIAA0284 exon, respectively. ITGB3 methylation was significantly decreased in the post-surgery (0.5 ± 0.5%) and lean controls (0 ± 0%) versus pre-surgery (13.6 ± 2.7%, P < 0.05). This decreased methylation post-surgery was associated with an increase in ITGB3 gene expression (fold change + 1.52, P = 0.0087). In addition, we showed that ITGB3 promoter methylation in vitro significantly suppressed transcriptional activity (P < 0.05). Transcription factor binding analysis for ITGB3 chr17.45,330,989 identified three putative transcription factor binding motifs; PAX-5, p53 and AP-2alphaA.ConclusionsThese results demonstrate that weight loss after RYGB alters the epigenome through DNA methylation. In particular, this study highlights ITGB3 as a novel gene that may contribute to the metabolic improvements observed post-surgery. Future additional studies are warranted to address the exact mechanism of ITGB3 in skeletal muscle.

Dataset Information

Time course metabolome of Roux-en-Y gastric bypass confirms correlation between leptin, body weight and the microbiome.

Publications

Time course metabolome of Roux-en-Y gastric bypass confirms correlation between leptin, body weight and the microbiome.

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