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Roux-en Y gastric bypass surgery induced genome-wide promoter specific changes in DNA methylation in whole blood of Obese patients

ABSTRACT: Twelve subjects were sampled before and six months after RYGB surgery to identify changes in the DNA methylation profile induced by the surgery. These changes were also compared to a reference methylome.

ORGANISM(S): Homo sapiens

SUBMITTER: Emil Nilsson

PROVIDER: E-MTAB-3161 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Intestinal microbiota after RYGB

Project description:Objective: Roux-Y gastric bypass (RYGB) surgery is a last treatment resort to induce substantial and sustained weight loss in severe obesity. The anatomical rearrangement affects the intestinal microbiota but so far, little information is available how it interferes with microbial functionality and microbial-host interaction independent from weight loss. Design: A RYGB rat model was utilized and compared to sham-operated controls which were kept at matched body weight as RYGB animals by food restriction. We assessed microbial taxonomy by 16S rRNA gene sequencing and functional activity by metaproteomics and metabolomics on microbiota samples collected separately from the ileum, the cecum as well as the colon and separately analysed the lumen and mucus associated microbiota. Results: Altered gut architecture in RYGB strongly affected the occurrence of Actinobacteria, especially Bifidobacteriaceae and Proteobacteria which were increased, whereas Firmicutes were decreased, although Streptococcaceae and Clostridium perfringens were observed at higher abundances. A decrease of conjugated as well as secondary bile acids was observed in the RYGB-gut lumen. In addition the arginine biosynthesis pathway in the microbiota was altered, indicated by the changes in abundance of upstream metabolites and enzymes, resulting in lower levels of arginine and higher levels of aspartate in the colon after RYGB. Conclusion: The anatomical rearrangement in RYGB affects microbiota composition and functionality by changes in amino acid and bile acid metabolism, independent of weight loss. The shift in microbiota taxonomic structure after RYGB may be mediated by the resulting change in composition of the bile acid pool in the gut lumen.

2020-03-17 | PXD013337 | Pride

Multi-organ systems study reveals Igfbp7 as a suppressor of gluconeogenesis after gastric bypass surgery

Project description:Roux-en-Y gastric bypass (RYGB) surgery reduces weight in obese patients. A marked decrease in blood glucose levels occurs before weight loss; however, key molecules that improve glycemic profile remain largely unknown. We used the RYGB surgery model in diet-induced obese (DIO) mice to monitor the proteome (with tandem mass tagging) of the Roux and biliopancreatic limbs, the liver and the pancreas up to four weeks after surgery, a time window associated with the early beneficial metabolic effects of the RYGB surgery model. The resulting kinetics were analyzed using high-dimensional cluster analysis that we recently developed (XINA,PMID: 30370770) to infer co-regulated proteins and pathways based on common kinetic profiles. Our analysis revealed the organs exhibited unique and common changes to their proteomes reflecting their specialized physiological roles and potential coordinated inter-organ crosstalk and responses, respectively. Further exploration of the Roux limb proteome kinetics included the identification of relatively unknown proteins found with clusters comprising established protein-protein interaction networks. One such protein was insulin-like growth factor binding protein 7 (Igfbp7) whose subsequent in vitro and in vivo studies supported the role of this secreted protein in suppressing hepatic gluconeogenesis; which in turn, substantiates our systems approach to discover new mechanisms by which the RYGB surgery exerts beneficial effects.

2020-01-23 | PXD015276 | Pride

RNA-Sequencing Characterisation of the Renal Cortical Response to Roux-en-Y Gastric Bypass Surgery Alone and Combined Roux-en-Y Gastric Bypass Surgery and Medical Therapy in the Zucker Diabetic Sprague Dawley Rat Model of Diabetic Kidney Disease

Project description:We report results from renal cortical transcriptomic analysis of responses to RYGB surgery alone and the combination of RYGB surgery and medical therapy in the Zucker Diabetic Sprague Dawley (ZDSD) rat model of diabetic kidney disease.

2021-03-17 | GSE147706 | GEO

Fecal Transplant from Roux-Y-Gastric-Bypass rat model into a diet induced obesity rat model

Project description:Investigating alterations the intestinal microbiome in a diet induced obesity (DIO) rat model after fecal transplant from rats, which underwent Roux-Y-Gastric-Bypass surgery (RYGB). The microbiomes of the RYGB-donor rats, the DIO rats, and DIO rats after receiving the fecal transplant from the RYGB rats. As controls lean rats as well as lean, RYGB and DIO rats after antibiotics treatment were used.

2022-08-12 | PXD026606 | Pride

Identification of Novel Changes in Human Skeletal Muscle Proteome following Roux-en-Y Gastric Bypass Surgery

Project description:The mechanisms of metabolic improvements following Roux-en-Y gastric bypass (RYGB) surgery are not entirely clear. Therefore, the aim of our study was to investigate the role of obesity and RYGB on the human skeletal muscle proteome.

2016-05-22 | GSE76468 | GEO

Goto-Kakizaki rats with Roux-en-Y gastric bypass surgery

Project description:Metabolic surgery has been increasingly recommended for obese diabetic patients, but questions remain as to its effectiveness for nonobese diabetic patients and its mechanism that leads to glucose homeostasis independently of weight loss. Roux-en-Y gastric bypass (RYGB), as one of the most effective metabolic operations, excludes a portion of stomach with the proximal intestine (biliopancreatic limb, BL) and rearranges the distal end of the intestine into a Y-configuration, in which food can flow from the upper stomach pouch through the Roux limb (RL). To address the above questions to RYGB surgery, we designed a series of surgical procedures in Goto-Kakizaki （GK） rats to assess the relationship between glycemic control independent of weight loss and RL length in the RYGB procedure and studied the molecular mechanism of the RL from a systematic and comprehensive view.

2020-02-10 | GSE126835 | GEO

Skeletal muscle gene expression changes one year following Roux-en-Y gastric bypass (RYGB) surgery

Project description:We used gene expression microarray to understand the gene expression changes in skeletal muscle one year follow RYGB weight loss surgery.

2020-11-18 | GSE161643 | GEO

Transcription profiling of rats subjected to Roux-en-Y gastruc bypass to characterize of weight loss and weight regain mechanisms

Project description:Roux-en-Y gastric bypass (RYGB) is the most effective therapy for morbid obesity, but it has a ~20% failure rate. We used our established RYGB model in diet-induced obese (DIO) Sprague-Dawley rats, which reproduces human bi-phasic body weight (BW) loss pattern, to determine mechanisms contributing to success (RGYB-S) or failed (RYGB-F) RYGB. DIO rats were randomized to RYGB, sham operated Obese, and sham operated obese pair fed-linked to RYGB (PF) groups. BW, caloric intake (CI) and fecal output (FO) were recorded daily for 90 days, food efficiency (FE) was calculated, and morphologic changes were determined. Gut, adipose and thyroid hormones were measured in plasma. Mitochondrial respiratory complexes in skeletal muscle, expression of energy-related hypothalamic and fat peptides, receptors and enzymes were quantified. A 25% failure rate occurred. RYGB-S, RYGB-F and PF rats vs. Obese showed rapid BW decrease, followed by sustained BW loss in RYGB-S. RYGB-F and PF gradually increased BW. Expression profiling of both CNS (hypothalamus) and peripheral tissues (subcutaneous abdominal fat) strongly supported the involvement of a number of metabolic and feeding-related genes in the differential outcomes. Experiment Overall Design: 3 biological replicate RNA samples were prepared from 2 tissues (the subcutaneous abdominal fat or the hypothalamus) from rats in 3 treatment groups (rats losing weight successfully after gastric bypass surgery, rats gaining weight, and rats that were fed the same amount as the treated rats)

2008-06-16 | E-GEOD-8314 | biostudies-arrayexpress

Weight Loss after Roux-En Y Gastric Bypass Surgery Reveals Novel Skeletal Muscle Promoter-Specific DNA Methylation Changes in Obese Patients

Project description:The 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.

2021-05-24 | GSE164305 | GEO

Roux-en-Y gastric bypass and caloric restriction but not gut hormone-based treatments profoundly impact the hypothalamic transcriptome in obese rats

Project description:Background: The hypothalamus is an important brain region for the regulation of energy balance. Roux-en-Y gastric bypass (RYGB) surgery and gut hormone-based treatments are known to reduce body weight, but their effects on hypothalamic gene expression and signaling pathways are poorly studied. Methods: Diet-induced obese male Wistar rats were randomized into the following groups: RYGB, sham-operation, sham + body weight-matched (BWM) to the RYGB group, osmotic minipump delivering PYY3-36 (0.1mg/kg/day), liraglutide s.c. (0.4mg/kg/day), PYY3-36+liraglutide and saline. All groups (except BWM) were kept on a free choice of high- and low-fat diets. Four weeks after interventions, hypothalami were collected for RNA-sequencing. Results: While rats in the RYGB, BWM and PYY3-36+liraglutide groups had comparable reductions in body weight, only RYGB and BWM treatment had a major impact on hypothalamic gene expression. In these groups, hypothalamic leptin receptor expression as well as the JAK–STAT, PI3K-Akt and AMPK signaling pathways were upregulated. No significant changes could be detected in PYY3-36+liraglutide, liraglutide and PYY treated groups. Conclusions: Despite causing similar body weight changes compared to RYGB and BWM, PYY3-36+liraglutide treatment does not impact hypothalamic gene expression. Whether this striking difference is favorable or unfavorable to metabolic health in the long term requires further investigation.

2022-01-14 | GSE190218 | GEO

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