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Roux-en-Y Gastric Bypass Reduces Podocyte Injury in Diabetic Kidney Disease

ABSTRACT: Roux-en-Y Gastric Bypass Reduces Podocyte Injury in Diabetic Kidney Disease

PROVIDER: PRJNA481023 | ENA |

REPOSITORIES: ENA

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Roux-en-Y Gastric Bypass Reduces Podocyte Injury in Diabetic Kidney Disease

Project description:Podocyte injury in diabetic kidney disease contributes to the development of albuminuria and subsequent renal decline. Clinically, gastric bypass surgery is associated with reductions in albuminuria, and rodent studies demonstrate coherent improvements in renal histology. We aimed to investigate the mechanisms underpinning remission of albuminuria following gastric bypass focussing on podocyte injury. Firstly, we tracked the evolution of albuminuria and cognate evidence of histological and ultrastructural damage to the glomerulus in male Zucker Diabetic Fatty rats. Secondly, we examined the impact of gastric bypass in these rats, focussing on podocyte injury. Thirdly, we conducted a global transcriptomic study profiling the shift in the renal transcriptome in the Zucker Diabetic Fatty rats rat and its relevance to human disease. Lastly, we explored whether gastric bypass could reverse the changes seen in the disease associated transcriptome. Albuminuria in the Zucker Diabetic Fatty rat developed by 12 weeks of age. This was accompanied by glomerulomegaly, podocyte stress and ultrastructural evidence of podocyte dedifferentiation. When animals underwent gastric bypass at 12 weeks of age, marked reductions in albuminuria in association with normalisation of glomerular tuft size, attenuation of podocyte stress and improvements in podocyte foot process morphology were observed within 2 months of surgery. A characteristic disease associated gene expression signature was observed in the kidneys of Zucker Diabetic Fatty rats, with a core set of alterations conserved in global analysis of the human DKD transcriptome. Many of the shared gene expression alterations were reversed by gastric bypass. Reductions in podocyte injury represent a key mechanism underpinning the remission of albuminuria following gastric bypass.

2019-07-10 | GSE117085 | GEO

Global Transcriptional Profiling of Women Following Roux-en-Y Gastric Bypass

Project description:Analysis of changes in gene expression after weight loss. The hypothesis tested in this study was that the weight loss caused by Roux-en-Y Gastric bypass may alter the expression of genes involved in multiple molecular pathways related to obesity. The results will generate important data for studies involving treatment of obesity, which is characterized as a multifactorial disease that affects thousands of individuals worldwide.

2017-09-03 | GSE83223 | GEO

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

Roux-en-Y Gastric Bypass Versus Loop Gastrojejunostomy for Malignant Gastric Outlet Obstruction

Project description:This study is intended to investigate whether roux-en-y bypass surgery is superior to conventional loop gastrojejunostomy for Malignant gastric outlet obstruction in terms of tolerance to solid food intake. We hypothesize that roux-en-y bypass will be associated with improved solid food intake in the first 30 days after surgery.

| 70610 | ecrin-mdr-crc

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

Weight loss following Roux-en-Y gastric bypass surgery leads to changes in the expression of several miRNAs and their predicted target genes in skeletal muscle

Project description:miRNA profiles were investigated in skeletal muscle in severely obese individuals with or without diabetes before and after Roux-en-Y gastric bypass surgery.

2024-01-22 | GSE87131 | GEO

Otsuka Long-Evans Tokushima fatty rats with Roux-en-Y gastric bypass surgery

Project description:Objective: The mechanisms underlying type 2 diabetes resolution after Roux-en-Y gastric bypass (RYGB) are unclear. We previously observed temporal migrations in small intestinal glycolysis, suggesting that glucose excretion may contribute to glucose homeostasis. This study aimed to evaluate the mechanisms underlying serum glucose excretion and its contribution to glucose homeostasis by using 2-deoxy-2-[18F]-fluoro-D-glucose (FDG) positron emission tomography. Design: FDG distribution in reconstructed intestinal limbs of sham- or RYGB-operated obese rats was identified. RNA sequencing was performed in areas of high or low FDG uptake.

2023-11-01 | GSE161404 | GEO

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

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

Project description:Goto-Kakizaki rats with Roux-en-Y gastric bypass surgery

| PRJNA523431 | ENA

Gastric bypass vs. ‘Medical Bypass’ - Impact on experimental diabetic kidney disease

Project description:Albuminuria is significantly reduced following Roux-en-Y gastric bypass (RYGB) surgery, suggesting a renoprotective effect of the intervention. Herein, we assess the relative impact of RYGB and RYGB equivalent non-surgical weight loss and glycaemic improvement on glomerular injury and global renal transcriptomic responses in the Zucker diabetic fatty rat (ZDF) model of diabetic nephropathy. We coined the term "medical bypass" (MB) to describe the intensive diet and pharmacotherapy based non-surgical intervention Adult ZDF rats underwent sham surgery (n=15) or RYGB (n=9). Nine sham-operated rats were calorie restricted and received insulin, liraglutide, metformin, ramipril, rosuvastatin and fenofibrate for 2 months (MB). Zucker fa/+ rats acted as healthy controls throughout. Bodyweight, glycaemia, albuminuria and glomerular injury specifically podocyte number, density and ultrastructure were assessed at follow up. Renal transcriptomes were compared by RNA-seq. RYGB resulted in 20-30% weight loss, normalized glycaemia and albuminuria and reduced indices of glomerular injury, specifically podocyte injury (foot process effacement). RYGB equivalent outcomes were obtained on all parameters following MB.

2019-07-10 | GSE117378 | GEO

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