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Alterations of DNA methylation profile in proximal jejunum potentially contribute to the beneficial effects of gastric bypass in a diabetic rat model

Published on Aug 1, 2019in Surgery for Obesity and Related Diseases3.758
· DOI :10.1016/J.SOARD.2019.05.027
Haijun Liu4
Estimated H-index: 4
(Southern Medical University),
Hong Zhang4
Estimated H-index: 4
(SJTU: Shanghai Jiao Tong University)
+ 3 AuthorsXueli Zhang4
Estimated H-index: 4
(Southern Medical University)
Abstract
Abstract Background The foregut theory posits that proximal small intestine plays an important role in the improvement of type 2 diabetes (T2D) after Roux-en-Y gastric bypass (RYGB). Objective To study the possible role of proximal jejunum in the treatment of T2D after RYGB via the analysis of DNA methylation and transcriptome. Setting Laboratories of Diabetes Institute. Methods Two batches of T2D rats undergoing surgeries (RYGB, and sham operation as control) were established independently. The proximal jejuna from one batch were used for the methylated DNA immunoprecipitation sequencing (MeDIP-seq) and transcriptome sequencing (RNA-seq). Those from another batch were used for DNA methylation analysis via a MassARRAY platform and quantitative polymerase chain reaction (qPCR) to verify the results of high-throughput sequencing analysis. Results The RNA-seq results showed that the genes differentially expressed (p 2). The Mogat3 in proximal jejunum after RYGB was obviously hypermethylated in the promoter region and its transcription level was significantly reduced. The results of the high-throughput sequencing were validated via methylation quantitative analysis and qPCR in a new set of samples. Conclusions RYGB could change DNA methylation and gene expression profiles in the proximal jejunum in T2D rats. Mogat3 potentially contributes to the beneficial effects caused by RYGB.
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References30
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#1Haijun Liu (Southern Medical University)H-Index: 4
#2Hong Zhang (SJTU: Shanghai Jiao Tong University)H-Index: 1
Last. Xueli Zhang (Southern Medical University)H-Index: 4
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Abstract Background Changes in gut microbiota induced by bariatric surgery have been associated with metabolic benefits. Objectives Our aim was to identify specific gut microbiota that may contribute to the improvement of type 2 diabetes (T2D) after Roux-en-Y gastric bypass (RYGB). Setting Laboratories of Shanghai Diabetes Institute and Shanghai Sixth People's Hospital. Methods Diabetic rats induced via a high-fat diet and low-dose streptozotocin administration were randomized to RYGB or sham su...
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#1Amita Bansal (UPenn: University of Pennsylvania)H-Index: 8
#2Sara E. PinneyH-Index: 10
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#1Priscila Sala (USP: University of São Paulo)H-Index: 8
#2G. Belarmino (USP: University of São Paulo)H-Index: 5
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ObjectiveTo describe the protocol of the SURgically induced Metabolic effects on the Human GastroIntestinal Tract (SURMetaGIT) study, a clinical pan-omics study exploring the gastrointestinal tract as a central organ driving remission of type 2 diabetes mellitus (T2DM) after Roux-en-Y gastric bypass (RYGB). The main points considered in the study’s design and challenges faced in its application are detailed.MethodsThis observational, longitudinal, prospective study involved collection of gastroi...
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#2Barbara Ernst (HSG: University of St. Gallen)H-Index: 14
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ContextDNA methylation has been proposed to play a critical role in many cellular and biological processes.ObjectiveTo examine the influence of Roux-en-Y gastric bypass (RYGB) surgery on genome-wid ...
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#2Yu Gao (UW: University of Wisconsin-Madison)H-Index: 4
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Summary Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries. Liver samples from morbidly obese patients (n = 45) with all stages of NAFLD and controls (n = 18) were analyzed by array-based DNA methylation and mRNA expression profiling. NAFLD-specific expression and methylation differences were seen for nine genes coding for key enzymes in intermediate metabolism (including PC , ACLY , and PLCG1 ) and insulin/insulin-like signaling (inclu...
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Summary DNA methylation provides a mechanism by which environmental factors can control insulin sensitivity in obesity. Here, we assessed DNA methylation in skeletal muscle from obese people before and after Roux-en-Y gastric bypass (RYGB). Obesity was associated with altered expression of a subset of genes enriched in metabolic process and mitochondrial function. After weight loss, the expression of the majority of the identified genes was normalized to levels observed in normal-weight, healthy...
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