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

ABSTRACT: 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.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE126835 | GEO | 2020/02/10

REPOSITORIES: GEO

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Gut Adaptation After Gastric Bypass in Humans Reveals Metabolically Significant Shift in Fuel Metabolism

Project description:Objective: Roux-en-Y gastric bypass surgery (RYGB) is among the most effective therapies for obesity and type 2 diabetes (T2D), and intestinal adaptation is a proposed mechanism for these effects. We hypothesized that intestinal adaptation precedes and relates to metabolic improvement in humans after RYGB. Methods: This was a prospective, longitudinal first-in-human study of gene expression (GE) in Roux limb (RL) collected surgically/endoscopically from 19 patients with and without diabetes. GE was determined by microarray across 6 postoperative months, including at an early postoperative (1 month  15 days) timepoint. Results: RL GE demonstrated tissue remodeling and metabolic reprogramming, including increased glucose and amino acid utilization. RL GE signatures were established early, before maximal clinical response, and persisted. Distinct GE fingerprints predicted concurrent and future improvements in HbA1c and in weight. Human RL exhibits GE changes characterized by anabolic growth and shift in metabolic substrate utilization. Paradoxically, anabolic growth in RL appears to contribute to the catabolic state elicited by RYGB. Conclusions: These data support a role for a direct effect of intestinal energy metabolism to contribute to the beneficial clinical effects of RYGB, suggesting that related pathways might be potential targets of therapeutic interest for patients with obesity with or without T2D.

2024-11-09 | GSE281144 | GEO

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

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2020-01-23 | PXD015276 | Pride

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.

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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.

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Systems Signature Reveals Unique Remission-path of Diabetes Generated by Gastric Bypass Surgery

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2017-12-13 | PXD008071 | Pride

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

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

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2016-05-22 | GSE76468 | GEO

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

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2022-08-12 | PXD026606 | 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

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2021-03-17 | GSE147706 | 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.

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