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.
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.
Project description:BackgroundInternal hernia (IH) is a common complication of laparoscopic Roux-en-Y gastric bypass (LRYGB). Little large-volume data exist on how to handle the mesenteric defects during LRYGB. This study evaluated long-term follow-up (5.5 years) of 2443 patients with primary closure of the mesenteric defects with a stapling device at LRYGB, in comparison with a non-closed group from the same centre.MethodsAll patients (N = 4013) undergoing LRYGB over a 10-year period (2005-2015) at a single institution were evaluated. The mesenteric defects were routinely closed starting June 2010. In total, 1570 non-closure patients and 2443 patients with stapled closure of the defects were prospectively entered and the results analysed.ResultsClosure of the mesenteric defects increased surgical time by 4 min and did not affect the 30-day complication rate. IH incidence was significantly lower (2.5%) in the closure group compared with 11.7% in the non-closure group, at 60 months. The relative risk reduction by closing the mesenteric defects was 4.09-fold (95% CI = 2.97-5.62) as calculated using a survival model.ConclusionsInternal hernia after LRYGB occurs frequently if mesenteric defects are left unclosed. Primary closure with a hernia-stapling device is safe and significantly reduces the risk of internal hernia.
Project description:IntroductionClosure of mesenteric defects during laparoscopic Roux-en-Y gastric bypass surgery (RYGB) has not been fully established as standard operative practice. However, in recent years a body of evidence has emerged suggesting that non-closure of defects leads to increased rates of internal herniation and its potential consequences, including the need for reoperation, along with an associated morbidity and mortality risk. Within the emerging literature there has also been some evidence of a greater risk of 30-day complications in closure groups. This systematic review and meta-analysis aims to look at the existing evidence and provide guidance on whether closure of mesenteric defects should be standard operative practice.MethodsThe systematic review and meta-analysis has been registered a priori. A literature search will be performed interrogating the Medline and Embase databases via Ovid, and also the Cochrane Controlled Register of Trials (CENTRAL), to identify randomised and non-randomised studies reporting comparative outcomes following closure vs. non-closure of mesenteric defects during RYGB. The primary outcome will be reoperation for small bowel obstruction, and secondary outcomes will include internal herniation, jejuno-jejunal anastomosis narrowing or kinking, adhesions, complications (<30?days and >30?days after surgery), 30-day mortality, reoperation, and any other outcome deemed relevant and reported in more than one study.
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.
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.
Project description:The role of the central nervous system in mediating metabolic effects of Roux-en-Y gastric bypass (RYGB) surgery is poorly understood. Using a rat model of RYGB, we aimed to identify changes in gene expression of key hypothalamic neuropeptides known to be involved in the regulation of energy balance.Lean male Sprague-Dawley rats underwent either RYGB or sham surgery. Body weight and food intake were monitored bi-weekly for 60 days post-surgery. In situ hybridization mRNA analysis of hypothalamic AgRP, NPY, CART, POMC and MCH was applied to RYGB and sham animals and compared with ad libitum fed and food-restricted rats. Furthermore, in situ hybridization mRNA analysis of dopaminergic transmission markers (TH and DAT) was applied in the midbrain.RYGB surgery significantly reduced body weight and intake of a highly palatable diet but increased chow consumption compared with sham operated controls. In the arcuate nucleus, RYGB surgery increased mRNA levels of orexigenic AgRP and NPY, whereas no change was observed in anorexigenic CART and POMC mRNA levels. A similar pattern was seen in food-restricted versus ad libitum fed rats. In contrast to a significant increase of orexigenic MCH mRNA levels in food-restricted animals, RYGB did not change MCH expression in the lateral hypothalamus. In the VTA, RYGB surgery induced a reduction in mRNA levels of TH and DAT, whereas no changes were observed in the substantia nigra relative to sham surgery.RYGB surgery increases the mRNA levels of hunger-associated signaling markers in the rat arcuate nucleus without concomitantly increasing downstream MCH expression in the lateral hypothalamus, suggesting that RYGB surgery puts a brake on orexigenic hypothalamic output signals. In addition, down-regulation of midbrain TH and DAT expression suggests that altered dopaminergic activity also contributes to the reduced intake of palatable food in RYGB rats.
Project description:Roux en Y gastric bypass (RYGB) surgery is currently the most effective therapy employed to treat obesity and its associated complications. In addition to weight loss and resolution of metabolic syndromes, such as diabetes, the RYGB procedure has been reported to increase alcohol consumption in humans. Using an outbred rodent model, we demonstrate that RYGB increases postsurgical ethanol consumption, that this effect cannot be explained solely by postsurgical weight loss and that it is independent of presurgical body weight or dietary composition. Altered ethanol metabolism and postsurgical shifts in release of ghrelin were also unable to account for changes in alcohol intake. Further investigation of the potential physiological factors underlying this behavioral effect identified altered patterns of gene expression in brain regions associated with reward following RYGB surgery. These findings have important clinical implications as they demonstrate that RYGB surgery leads directly to increased alcohol intake in otherwise alcohol nonpreferring rat and induces neurobiological changes in brain circuits that mediate a variety of appetitive behaviors.
Project description:We report a 66-year-old male with a history of Roux-en-Y gastric bypass surgery who began dabigatran for new onset atrial fibrillation. After 5 weeks of therapy, his transesophageal echocardiogram prior to electrocardioversion showed severe spontaneous echo contrast. Cardioversion was postponed and anticoagulant therapy was continued. The following day, he suffered a thromboembolic stroke. Concern arose that postoperative malabsorption could have resulted in subtherapeutic anticoagulation. This notion was strengthened by a second patient who had subtherapeutic serum levels despite maximal dosing. To the best of our knowledge, we are the first to report impaired absorption of dabigatran following Roux-en-Y gastric bypass surgery. <Learning objective: Dabigatran has a predictable pharmacokinetic profile, allowing for a fixed-dose regimen that does not require frequent monitoring or dietary modifications. However, its absorption in patients who have undergone Roux-en-Y gastric bypass surgery has not been studied. Postoperative malabsoprtion, a major complication following Roux-en-Y gastric bypass surgery, can result in inadequate anticoagulation. As a result of unpredictable absorption, strategies allowing for routine monitoring may be best in this population.>.