Long-term changes in adipose tissue gene expression following bariatric surgery
ABSTRACT: In order to identify mechanisms underlying the long-term beneficial effect of bariatric surgery on abdominal subcutaneous WAT, we performed gene microarray analyses on adipose tissue from a cohort of obese women. Adipose tissue biopsies were obtained before RYGB, and then 2 and 5 years thereafter. To evaluate the long-term effect of Roux-en-Y gastric bypass (RYGB) surgery on WAT, we also compared the WAT gene expression at 5 years postsurgery with that of age-matched nonoperated women. Overall design: Transcriptomic profiling by gene microarray was performed in abdominal subcutaneous WAT from women before (n = 50) and two (n = 49) and five (n = 38) years after Roux-en-Y gastric bypass (RYGB) surgery as well as in 28 age-matched nonoperated women.
INSTRUMENT(S): [Clariom_D_Human] Affymetrix Human Clariom D Assay [transcript (gene) version]
Project description:BACKGROUND:Gastric cancer is an extremely rare condition to occur after bariatric surgery, and most of the reported cases are adenocarcinomas. Regarding gastrointestinal stromal tumors (GISTs), there are only two reported cases occurring after bariatric surgery (one after gastric banding and the other following Roux-en-Y gastric bypass (RYGB)). CASE PRESENTATION:A 48-year-old woman with previous history of obesity and type 2 diabetes, treated with a Roux-en-Y gastric bypass 2 years earlier, was referred to our center due to complains of diffuse abdominal pain and distension associated with asthenia. Magnetic resonance imaging showed a cystic-solid mass located in the right hypochondrium, measuring 19.5 × 13.5 × 16 cm, suggesting the diagnosis of a retroperitoneal tumor. Based on these findings, a laparotomy, evidencing that the larger cystic-solid tumor was originating from the excluded stomach post-RYGB. The gastrectomy of the excluded stomach was performed aside with a conventional cholecystectomy. Histopathology and immunohistochemistry confirmed to be a gastric GIST with epithelioid cells. Currently, 12 months after surgery, the patient presents no signs of recurrence. CONCLUSION:This is the second case of gastric GIST occurring after RYGB to be reported in the literature.
Project description:Roux-en-Y gastric bypass (RYGB) is an effective method of weight loss and remediation of type-2 diabetes; however, the mechanisms leading to these improvements are unclear. Additionally, adipocytes within white adipose tissue (WAT) depots can manifest characteristics of brown adipocytes. These 'BRITE/beige' adipocytes express uncoupling protein 1 (UCP1) and are associated with improvements in glucose homeostasis and protection from obesity. Interestingly, atrial and B-type natriuretic peptides (NPs) promote BRITE/beige adipocyte enrichment of WAT depots, an effect known as "browning." Here, we investigate the effect of RYGB surgery on NP, NP receptors, and browning in the gonadal adipose tissues of female mice. We propose that such changes may lead to improvements in metabolic homeostasis commonly observed following RYGB.Wild type, female, C57/Bl6 mice were fed a 60% fat diet ad libitum for six months. Mice were divided into three groups: Sham operated (SO), Roux-en-Y gastric bypass (RYGB), and Weight matched, sham operated (WM-SO). Mice were sacrificed six weeks following surgery and evaluated for differences in body weight, glucose homeostasis, adipocyte morphology, and adipose tissue gene expression.RYGB and calorie restriction induced similar weight loss and improved glucose metabolism without decreasing food intake. ?3-adrenergic receptor expression increased in gonadal adipose tissue, in addition to Nppb (BNP), and NP receptors, Npr1, and Npr2. The ratio of Npr1:Npr3 and Npr2:Npr3 increased in RYGB, but not WM-SO groups. Ucp1 protein and mRNA, as well as additional markers of BRITE/beige adipose tissue and lipolytic genes increased in RYGB mice to a greater extent than calorie-restricted mice.Upregulation of Nppb, Npr1, Npr2, and ?3-adrenergic receptors in gonadal adipose tissue following RYGB was associated with increased markers of browning. This browning of gonadal adipose tissue may underpin the positive effect of RYGB on metabolic parameters and may in part be mediated through upregulation of natriuretic peptides.
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)
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. Keywords: gene expression analysis 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)
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. Overall design: Basal muscle biopsies were obtained from seven obese (BMI >40 kg/m2) female subjects (45.1±3.6 years) pre- and 3 months post-RYGB, and euglycemic-hyperinsulinemic clamps were used to assess insulin sensitivity.
Project description:BACKGROUND:Weight loss outcomes after bariatric surgery are less favorable in super morbidly obese patients (BMI ?50?kg/m2). Non-response, either defined as insufficient weight loss or weight regain after initial successful weight loss, is a matter of serious concern in these patients. The primary banded Roux-en-Y gastric bypass has shown promising results regarding weight loss in the bariatric population. However, up to now, long-term comparative data about the banded and non-banded bypass in superobese patients is lacking. The aim of this study is to assess the added value of the banded Roux-en-Y gastric bypass in superobese patients on long-term weight loss outcomes. METHODS:This single center study will evaluate superobese patients who receive a non-banded Roux-en-Y gastric bypass (NB-RYGB) and a banded Roux-en-Y gastric bypass (B-RYGB). Data from the NB-RYGB group will be collected in retrospect, while data from the B-RYGB group will be collected prospectively. When performing a B-RYGB, a 7.0-8.0?cm silastic ring (MiniMizer®) will be placed proximal to the gastrojejunostomy. The main outcomes of this study are weight loss and non-response during a 10?year follow-up period. Secondary outcomes are reduction of obesity related comorbidities and medication, (ring-related) morbidity and mortality, complications, re-operations, patient satisfaction and health-related quality of life. A total of 142 patients will be included in this study. DISCUSSION:This study will help establish the clinical utility of the B-RYGB in superobese patients. TRIAL REGISTER:NL8093. Registered 15 October 2019 - Retrospectively registered on the Dutch Registry of Clinical trials, www.trialregister.nl.
Project description:Gastric bypass surgery is an effective therapy for extreme obesity. However, substantial variability in weight loss outcomes exists that remains largely unexplained. Our objective was to determine whether any commonly collected preoperative clinical variables were associated with weight loss following Roux-en-Y gastric bypass (RYGB) surgery.The analysis was based on a prospectively recruited observational cohort of 2,365 patients who underwent Roux-en-Y gastric bypass surgery from 2004 to 2009. Weight loss was stratified into three major phases, early (0-6 months), nadir, and long-term (>36 months). Multivariate regression models were constructed using a database of over 350 variables.A total of 12-14 preoperative variables were independently associated (P?<?0.05) with each of the temporal weight loss phases. Preoperative variables associated with poorer nadir and long-term weight loss included higher baseline BMI, higher preoperative weight loss, iron deficiency, use of any diabetes medication, nonuse of bupropion medication, no history of smoking, age >50 years, and the presence of fibrosis on liver biopsy.Several variables previously associated with poorer weight loss after RYGB surgery including age, baseline BMI, and type 2 diabetes were replicated. Several others suggest possible clinical interventions for postoperative management of RYGB patients to improve weight loss outcomes.
Project description:Morbidly obese individuals are predisposed to a wide range of disorders, including type 2 diabetes, atherosclerotic cardiovascular disease, fatty liver disease, and certain cancers. Remarkably, all of these disorders can be improved or prevented by Roux-en-Y gastric bypass (RYGB) surgery. We have reported that decreased AMPK activity, together with increased oxidative stress and inflammation in adipose tissue, is associated with insulin resistance in morbidly obese bariatric surgery patients. In the current study, we assessed how these parameters are affected by RYGB surgery. Eleven patients (average age of 46 ± 4 years) were studied immediately prior to surgery and 3 months postoperatively. We measured subcutaneous adipose tissue AMPK phosphorylation (threonine 172, an index of its activation), malonyl-CoA content, protein carbonylation (a marker of oxidative stress), plasma adiponectin, and mRNA expression of several inflammatory cytokines. After surgery, AMPK activity increased 3.5-fold and oxidative stress decreased by 50% in subcutaneous adipose tissue. In addition, malonyl-CoA levels were reduced by 80%. Furthermore, patients had improvements in their BMI and insulin sensitivity (HOMA) and had increased circulating high-molecular weight adiponectin and decreased fasting plasma insulin levels. In contrast, the expression of inflammatory markers in subcutaneous adipose tissue was unchanged postoperatively, although plasma CRP was diminished by 50%.
Project description:Despite of its significant therapeutic effects on obesity and metabolic diseases, Roux-en-Y gastric bypass (RYGB) has limited clinical application because of considerable impacts on the gastrointestinal structure and postoperative complications. This study aims to develop a simplified surgical approach with less damage and complication but efficient metabolic benefit.The effects of Esophagus-Duodenum gastric bypass (EDGB) on body weight, food intake, glucose and lipid metabolism were compared to RYGB in mice.EDGB is simple, has higher survival rate and less complication. Relative to RYGB, EDGB demonstrated modest body weight control, identical improvement of glucose and lipid metabolism in obese mice. Blood glucose increased significantly 15 and 30min after oral glucose administration, then markedly decreased in both EDGB and RYGB groups relative to the sham surgery, indicating a quicker absorption of oral glucose and improvement in glucose uptake by insulin targeted tissues. Insulin sensitivity was identically improved. EDGB significantly decreased plasma and hepatic triglyceride levels, while increased browning in visceral and subcutaneous white adipose tissue to the extent identical to RYGB. Levels of ghrelin and nesfatin-1 increased significantly after EDGB and RYGB.EDGB is a valuable model to study the metabolic benefit of bariatric surgery in mice.
Project description:The effects of various weight loss strategies on pancreatic beta cell function remain unclear. We aimed to compare the effect of intensive lifestyle intervention (ILI) and Roux-en-Y gastric bypass surgery (RYGB) on beta cell function.One year controlled clinical trial (ClinicalTrials.gov identifier NCT00273104).One hundred and nineteen morbidly obese participants without known diabetes from the MOBIL study (mean (s.d.) age 43.6 (10.8) years, body mass index (BMI) 45.5 (5.6) kg/m², 84 women) were allocated to RYGB (n = 64) or ILI (n = 55). The patients underwent repeated oral glucose tolerance tests (OGTTs) and were categorised as having either normal (NGT) or abnormal glucose tolerance (AGT). Twenty-nine normal-weight subjects with NGT (age 42.6 (8.7) years, BMI 22.6 (1.5) kg/m², 19 women) served as controls. OGTT-based indices of beta cell function were calculated.One year weight reduction was 30% (8) after RYGB and 9% (10) after ILI (P < 0.001). Disposition index (DI) increased in all treatment groups (all P<0.05), although more in the surgery groups (both P < 0.001). Stimulated proinsulin-to-insulin (PI/I) ratio decreased in both surgery groups (both P < 0.001), but to a greater extent in the surgery group with AGT at baseline (P < 0.001). Post surgery, patients with NGT at baseline had higher DI and lower stimulated PI/I ratio than controls (both P < 0.027).Gastric bypass surgery improved beta cell function to a significantly greater extent than ILI. Supra-physiological insulin secretion and proinsulin processing may indicate excessive beta cell function after gastric bypass surgery.