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: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.
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.
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.
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: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.
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:Roux-en-Y gastric bypass surgery in Zucker rats induces bacterial and systemic metabolic changes independent of caloric restriction-induced weight loss
Project description:To map the genetics of gene expression in metabolically relevant tissues and investigate the diversity of expression SNPs (eSNPs) in multiple tissues from the same individual, we collected four tissues from approximately 1,000 patients undergoing Roux-en-y gastric bypass and clinical traits associated with their weight loss and co-morbidities. We then performed high-throughput genotyping and gene expression profiling and carried out a genome-wide association analyses for more than one hundred thousand gene expression traits representing four metabolically relevant tissues; liver, omental adipose, subcutaneous adipose and stomach. We successfully identified 24,531 eSNPs corresponding to ~10,000 distinct genes. This represents the greatest number of eSNPs identified to our knowledge by any study to date and the first study to identify eSNPs from stomach tissue. We then demonstrate how these eSNPs provide a high quality disease map for each tissue in morbidly obese patients to not only inform genetic associations indentified in this cohort, but in previously published genome wide association studies as well. eSNPs and gene co-expression modules identification in morbidly obese patients represent a great resource that will aid in elucidating the key networks associated with morbid obesity, response to RYGB and disease as a whole. Keywords: Tissue profiling in a human cohort. Liver tissue was collected from patients at the time of RYGB surgery at Massachusetts General Hospital between 2000 and 2007. Samples were collected in RNAlater (Ambion/Applied Biosystems), stored at -80° and shipped to Rosetta Inpharmatics Gene Expression Laboratory Seattle, WA for extraction, amplification, labeling, and microarray processing. Samples processed ranged in size from 100-200mg. Total RNA extracted from liver was converted to fluorescently labeled cRNA that was hybridized to custom 44K DNA oligonucleotide microarrays manufactured by Agilent Technologies as described previously (Hughes et al. 2001; Schadt et al. 2008). Successful gene expression profiling results were collected from 651 liver samples.