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

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

PROVIDER: PRJNA481953 | ENA |

REPOSITORIES: ENA

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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

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

Bypass and diabetic kidney disease

Project description:Bypass and diabetic kidney disease

| PRJNA481952 | ENA

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

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

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

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RNA-Sequencing Characterisation of the Renal Cortical Response to Diet-Induced Weight Loss 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 diet-induced weight loss plus medical therapy in the Zucker Diabetic Sprague Dawley (ZDSD) rat model of diabetic kidney disease.

2022-03-14 | GSE169085 | GEO

Project description: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

| PRJNA616151 | ENA

Gastric Bypass and the Microbiome

Project description:Gastric Bypass and the Microbiome

| PRJEB50752 | ENA

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

FGF19 as a Surgical Factor Contributing to the Metabolic Effects of Gastric Bypass Surgery

Project description:Gastric bypass surgery has proven to be the most effective treatment in controlling hyperglycemia in severely obese patients with diabetes. Here we show that FGF19, a gut hormone, is rapidly induced by bypass surgery in rodents and humans. Administration of FGF19 achieves remission of diabetes through mechanisms beyond weight loss in animal models of diabetes, supporting a role of FGF19 as part of hormonal changes that influence metabolism following surgery. Through an unbiased phenotypic screen in diabetic mice, we identified selective, safe and effective FGF19 analogues. Unexpectedly, FGF19 analogue failed to correct hyperglycemia in patients with type 2 diabetes. In contrast, administration of FGF19 analogue resulted in rapid, robust and sustained improvement in liver fat content and histology in patients with non-alcoholic steatohepatitis, faithfully replicating effect of the surgery. Thus, our work identifies a strategy of replacing gastric bypass surgery by equally effective, but less invasive, treatment for non-alcoholic steatohepatitis. We used microarrays to detail the global programme of gene expression affected by gastric bypass surgery in rats.

2021-09-25 | GSE120530 | GEO

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