Time-dependent molecular responses differ between gastric bypass and dieting but are conserved across species
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA454673 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7087260.fastq.gz | Fastqsanger.gz | |||
| SRR7087270.fastq.gz | Fastqsanger.gz | |||
| SRR7087280.fastq.gz | Fastqsanger.gz | |||
| SRR7087290.fastq.gz | Fastqsanger.gz | |||
| SRR7087300.fastq.gz | Fastqsanger.gz |
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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
Project description:Gastric Bypass and the Microbiome
| PRJEB50752 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-07-09 | GSE113823 | GEO
Project description:The effectiveness of Roux-en-Y gastric bypass (RYGB) against obesity and its comorbidities has generated excitement about developing new, less invasive treatments that use the same molecular mechanisms. Although controversial, RYGB-induced improvement of metabolic function may not depend entirely upon weight loss. To elucidate the differences between RYGB and dieting, we studied several individual organ molecular responses and generated an integrative, interorgan view of organismal physiology. We also compared murine and human molecular signatures. We show that, although dieting and RYGB can bring about the same degree of weight loss, post-RYGB physiology is very different. RYGB induces distinct, organ-specific adaptations in a temporal pattern that is characterized by energetically demanding processes, which may be coordinated by HIF1a activation and the systemic repression of growth hormone receptor signaling. Many of these responses are conserved in rodents and humans and may contribute to the remarkable ability of surgery to induce and sustain metabolic improvement.
| S-EPMC6628900 | biostudies-literature
Project description:Obesity results from a chronic imbalance between energy intake and energy expenditure, with excess calories stored as fat. As such, weight loss has long been considered as a primary goal of treatment for obesity. A surgical treatment of severe obesity such as gastric bypass provides the most dramatic reductions in body weight, and a well-known effect of weight loss is an improvement in insulin sensitivity. However, the molecular mechanism underlying this association remains unclear. Thus, we profiled skeletal muscle of morbidly obese patients before and after gastric bypass surgery. Results from this project will provide global patterns of gene expression with weight loss, which help to understand the pathogenesis of obesity at the molecular level. Keywords: Time-Series
2006-06-20 | GSE5109 | GEO
Project description:Gastric bypass vs. ‘Medical Bypass’ - Impact on experimental diabetic kidney disease
| PRJNA481953 | ENA
Project description:Objective: Adipose tissue plays a key role in obesity related metabolic dysfunction. MicroRNA (miRNA) are gene regulatory molecules involved in inter-cellular and inter-organ communication. We hypothesised that miRNA levels in adipose tissue would change after gastric bypass surgery and that this would provide insights into their role in obesity-induced metabolic dysregulation. Methods: miRNA-profiling (Affymetrix_Gene-Chip_miRNA2.0_Arrays) of omental and subcutaneous adipose (n=15 females) before, and after, gastric bypass surgery. Results: One omental, and thirteen subcutaneous adipose miRNAs were significantly, differentially expressed after gastric bypass, including down-regulation of miR-223-3p and its antisense relative, miR-223-5p, in both adipose tissues. mRNA levels of miR-223-3p targets NLRP3 and GLUT4 were increased and decreased respectively following gastric bypass in both adipose tissues. Significantly more NLRP3 protein was observed in omental adipose after gastric bypass (P=0.02). Significant hypomethlyation of NLRP3 and hypermethylation of miR-223 was observed in both adipose tissues after gastric bypass. In subcutaneous adipose significant correlations were observed between both miR-223-3p and miR-223-5p and glucose, and between NLRP3 mRNA and protein levels and blood lipids. Conclusions: This is the first report detailing genome-wide miRNA-profiling of omental adipose before and after gastric bypass, and further highlights a link between miR-223-3p and the NLRP3 inflammasome in obesity.
2019-12-16 | E-MTAB-8594 | biostudies-arrayexpress
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
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
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