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Reduction in inflammatory gene expression in skeletal muscle from Roux-en-Y gastric bypass patients randomized to omentectomy.
Tamboli RA, Hajri T, Jiang A, Marks-Shulman PA, Williams DB, Clements RH, Melvin W, Bowen BP, Shyr Y, Abumrad NN, Flynn CR
(2011) PLoS One 6: e28577
MeSH Terms: Adolescent, Adult, Anthropometry, Biomarkers, Cluster Analysis, Female, Gastric Bypass, Gene Expression Profiling, Gene Expression Regulation, Humans, Inflammation, Male, Middle Aged, Muscle, Skeletal, Oligonucleotide Array Sequence Analysis, Omentum, Reproducibility of Results, Signal Transduction, Young Adult
Show Abstract · Added December 10, 2013
OBJECTIVES - To examine the effects of Roux-en-Y gastric bypass (RYGB) surgery with and without laparoscopic removal of omental fat (omentectomy) on the temporal gene expression profiles of skeletal muscle.
DESIGN - Previously reported were the whole-body metabolic effects of a randomized, single-blinded study in patients receiving RYGB surgery stratified to receive or not receive omentectomy. In this follow up study we report on changes in skeletal muscle gene expression in a subset of 21 patients, for whom biopsies were collected preoperatively and at either 6 months or 12 months postoperatively.
METHODOLOGY/PRINCIPAL FINDINGS - RNA isolated from skeletal muscle biopsies of 21 subjects (8 without omentectomy and 13 with omentectomy) taken before RYGB or at 6 and 12 months postoperatively were subjected to gene expression profiling via Exon 1.0 S/T Array and Taqman Low Density Array. Robust Multichip Analysis and gene enrichment data analysis revealed 84 genes with at least a 4-fold expression difference after surgery. At 6 and 12 months the RYGB with omentectomy group displayed a greater reduction in the expression of genes associated with skeletal muscle inflammation (ANKRD1, CDR1, CH25H, CXCL2, CX3CR1, IL8, LBP, NFIL3, SELE, SOCS3, TNFAIP3, and ZFP36) relative to the RYGB non-omentectomy group. Expressions of IL6 and CCL2 were decreased at all postoperative time points. There was differential expression of genes driving protein turnover (IGFN1, FBXW10) in both groups over time and increased expression of PAAF1 in the non-omentectomy group at 12 months. Evidence for the activation of skeletal muscle satellite cells was inferred from the up-regulation of HOXC10. The elevated post-operative expression of 22 small nucleolar RNAs and the decreased expression of the transcription factors JUNB, FOS, FOSB, ATF3 MYC, EGR1 as well as the orphan nuclear receptors NR4A1, NR4A2, NR4A3 suggest dramatic reorganizations at both the cellular and genetic levels.
CONCLUSIONS/SIGNIFICANCE - These data indicate that RYGB reduces skeletal muscle inflammation, and removal of omental fat further amplifies this response.
TRIAL REGISTRATION - ClinicalTrials.gov NCT00212160.
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19 MeSH Terms
Hepatic and peripheral insulin sensitivity and diabetes remission at 1 month after Roux-en-Y gastric bypass surgery in patients randomized to omentectomy.
Dunn JP, Abumrad NN, Breitman I, Marks-Shulman PA, Flynn CR, Jabbour K, Feurer ID, Tamboli RA
(2012) Diabetes Care 35: 137-42
MeSH Terms: Adult, Blood Glucose, Diabetes Mellitus, Type 2, Female, Gastric Bypass, Glucose Clamp Technique, Humans, Insulin Resistance, Liver, Male, Middle Aged, Obesity, Omentum, Remission Induction, Treatment Outcome, Weight Loss
Show Abstract · Added December 10, 2013
OBJECTIVE - Early after Roux-en-Y gastric bypass (RYGB), there is improvement in type 2 diabetes, which is characterized by insulin resistance. We determined the acute effects of RYGB, with and without omentectomy, on hepatic and peripheral insulin sensitivity. We also investigated whether preoperative diabetes or postoperative diabetes remission influenced tissue-specific insulin sensitivity after RYGB.
RESEARCH DESIGN AND METHODS - We studied 40 obese (BMI 48 ± 8 kg/m(2)) participants, 17 with diabetes. Participants were randomized to RYGB alone or in conjunction with omentectomy. Hyperinsulinemic-euglycemic clamps with isotopic-tracer infusion were completed at baseline and at 1 month postoperatively to assess insulin sensitivity.
RESULTS - Participants lost 11 ± 4% of body weight at 1 month after RYGB, without an improvement in peripheral insulin sensitivity; these outcomes were not affected by omentectomy, preoperative diabetes, or remission of diabetes. Hepatic glucose production (HGP) and the hepatic insulin sensitivity index improved in all subjects, irrespective of omentectomy (P ≤ 0.001). Participants with diabetes had higher baseline HGP values (P = 0.003) that improved to a greater extent after RYGB (P = 0.006). Of the 17 participants with diabetes, 10 (59%) had remission at 1 month. Diabetes remission had a group × time effect (P = 0.041) on HGP; those with diabetes remission had lower preoperative and postoperative HGP.
CONCLUSIONS - Peripheral insulin sensitivity did not improve 1 month after RYGB, irrespective of omentectomy, diabetes, or diabetes remission. Hepatic insulin sensitivity improved at 1 month after RYGB and was more pronounced in patients with diabetes. Improvement in HGP may influence diabetes remission early after RYGB.
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16 MeSH Terms
Reduction of 8-iso-prostaglandin F2α in the first week after Roux-en-Y gastric bypass surgery.
Ueda Y, Hajri T, Peng D, Marks-Shulman PA, Tamboli RA, Shukrallah B, Saliba J, Jabbour K, El-Rifai W, Abumrad NA, Abumrad NN
(2011) Obesity (Silver Spring) 19: 1663-8
MeSH Terms: Dinoprost, Extracellular Fluid, Gastric Bypass, Glutathione Peroxidase, Humans, Interleukin-6, Intra-Abdominal Fat, Obesity, Oxidative Stress, Postoperative Period, Subcutaneous Fat, Weight Loss
Show Abstract · Added December 5, 2013
Obesity is associated with increased markers of oxidative stress. We examined whether oxidative stress is reduced within the first week after Roux-en-Y gastric bypass (RYGB) surgery and could be related to changes in adipose tissue depots. The reactive oxygen species (ROS) marker 8-iso-prostaglandin F2α (8-iso-PGF2α) and activity of antioxidant glutathione peroxidases (GPX) in plasma were compared before and ~1 week after RYGB. The effects of RYGB on subcutaneous adipose tissue and interstitial fluid 8-iso-PGF2α levels and subcutaneous adipose tissue expression of GPX-3 were also assessed. Levels of 8-iso-PGF2α in subcutaneous and visceral adipose tissue were determined. Plasma 8-iso-PGF2α levels decreased (122 ± 75 to 56 ± 15 pg/ml, P = 0.001) and GPX activity increased (84 ± 18 to 108 ± 25 nmol/min/ml, P = 0.003) in the first week post-RYGB. RYGB also resulted in reductions of 8-iso-PGF2α in subcutaneous adipose tissue (1,742 ± 931 to 1,132 ± 420 pg/g fat, P = 0.046) and interstitial fluid (348 ± 118 to 221 ± 83 pg/ml, P = 0.046) that were comparable to plasma (26-33%, P = 0.74). Adipose GPX-3 expression was increased (6.7 ± 4.7-fold, P = 0.004) in the first postoperative week. The improvements in oxidative stress occurred with minimal weight loss (2.4 ± 3.4%, P = 0.031) and elevations in plasma interleukin-6 (18.0 ± 46.8 to 28.0 ± 58.9 pg/ml, P = 0.004). Subcutaneous and visceral adipose tissues express comparable 8-iso-PGF2α levels (1,204 ± 470 and 1,331 ± 264 pg/g fat, respectively; P = 0.34). These data suggest that RYGB affects adipose tissue leading to the restoration of adipose redox balance within the first postoperative week and that plasma 8-iso-PGF2α is primarily derived from subcutaneous adipose tissue.
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12 MeSH Terms
Role of the foregut in the early improvement in glucose tolerance and insulin sensitivity following Roux-en-Y gastric bypass surgery.
Hansen EN, Tamboli RA, Isbell JM, Saliba J, Dunn JP, Marks-Shulman PA, Abumrad NN
(2011) Am J Physiol Gastrointest Liver Physiol 300: G795-802
MeSH Terms: Adult, Anastomosis, Roux-en-Y, Area Under Curve, Blood Glucose, Body Weight, Diabetes Mellitus, Type 2, Duodenum, Female, Food, Gastric Bypass, Ghrelin, Glucagon-Like Peptide 1, Glucose Tolerance Test, Humans, Incretins, Insulin, Insulin Resistance, Jejunum, Laparoscopy, Male, Metabolism, Middle Aged
Show Abstract · Added December 5, 2013
Bypass of the foregut following Roux-en-Y gastric bypass (RYGB) surgery results in altered nutrient absorption, which is proposed to underlie the improvement in glucose tolerance and insulin sensitivity. We conducted a prospective crossover study in which a mixed meal was delivered orally before RYGB (gastric) and both orally (jejunal) and by gastrostomy tube (gastric) postoperatively (1 and 6 wk) in nine subjects. Glucose, insulin, and incretin responses were measured, and whole-body insulin sensitivity was estimated with the insulin sensitivity index composite. RYGB resulted in an improved glucose, insulin, and glucagon-like peptide-1 (GLP-1) area under the curve (AUC) in the first 6 wk postoperatively (all P ≤ 0.018); there was no effect of delivery route (all P ≥ 0.632) or route × time interaction (all P ≥ 0.084). The glucose-dependent insulinotropic polypeptide (GIP) AUC was unchanged after RYGB (P = 0.819); however, GIP levels peaked earlier after RYGB with jejunal delivery. The ratio of insulin AUC to GLP-1 and GIP AUC decreased after surgery (P =.001 and 0.061, respectively) without an effect of delivery route over time (both P ≥ 0.646). Insulin sensitivity improved post-RYGB (P = 0.001) with no difference between the gastric and jejunal delivery of the mixed meal over time (P = 0.819). These data suggest that exclusion of nutrients from the foregut with RYGB does not improve glucose tolerance or insulin sensitivity. However, changes in the foregut response post-RYGB due to lack of nutrient exposure cannot be excluded. Our findings suggest that foregut bypass may alter the incretin response by enhanced nutrient delivery to the hindgut.
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22 MeSH Terms
Regional fat changes following weight reduction from laparoscopic Roux-en-Y gastric bypass surgery.
Miller GD, Carr JJ, Fernandez AZ
(2011) Diabetes Obes Metab 13: 189-92
MeSH Terms: Body Weight, Female, Gastric Bypass, Humans, Laparoscopy, Middle Aged, Obesity, Morbid, Weight Loss
Show Abstract · Added February 28, 2014
Fat accumulation in muscle (intermuscular, IM) and viscera plays a role in obesity comorbidities. This study examined the impact of Roux-en-Y gastric bypass (RYGB) surgery in morbid obesity on changes in regional fat and muscle depots, and these body composition markers were correlated with physical function. Women (n = 18) were assessed prior to (baseline) and 12 months following RYGB for regional body composition and physical function. Weight loss from baseline to 12 months was 33.7 (s.e.m. = 1.7)%; total body fat decreased from 86.8 (s.e.m. = 5.8) to 45.8 (s.e.m. = 3.9) kg during follow-up. Differential changes in regional body fat were apparent with a volume loss of 58.4% in visceral fat, 19.8% in abdomen IM fat and 50.7% in thigh IM fat. At baseline, abdomen IM fat volume was related to physical function. There was less loss of abdomen IM fat volume than other depots following surgery; furthermore its relationship with physical function is a novel finding.
1 Communities
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8 MeSH Terms
Gastrostomy-to-gastrojejunostomy tube conversion: impact of the method of original gastrostomy tube placement.
Kim CY, Patel MB, Miller MJ, Suhocki PV, Balius A, Smith TP
(2010) J Vasc Interv Radiol 21: 1031-7
MeSH Terms: Adolescent, Adult, Aged, Aged, 80 and over, Combined Modality Therapy, Female, Gastric Bypass, Gastrostomy, Humans, Male, Middle Aged, Prosthesis Implantation, Radiography, Interventional, Treatment Outcome, Young Adult
Show Abstract · Added June 14, 2016
PURPOSE - To determine the outcome of gastrostomy tube-to-gastrojejunostomy tube conversion on the basis of the method of original gastrostomy tube placement.
MATERIALS AND METHODS - One hundred twenty-four patients (age range, 13-87 years; 72 male and 52 female patients) underwent conversion of a primarily placed gastrostomy tube to a gastrojejunostomy tube at the authors' institution between January 2000 and December 2008. The method of original gastrostomy tube placement was radiologic (n = 27), endoscopic (n = 75), laparoscopic (n = 2), or open surgery (n = 20). The method of placement was correlated with the success rates of gastrostomy-to-gastrojejunostomy tube conversion. Medical records and radiologic images were reviewed to determine the frequency of proximal migration of the jejunostomy tube into the stomach. Follow-up data were available for an average of 136 days after gastrostomy-to-gastrojejunostomy tube conversion (median, 63 days; range, 1-1,300 days).
RESULTS - Of 124 gastrostomy tube-to-gastrojejunostomy tube conversions, 109 (87.9%) were successfully performed. Procedural conversion failure occurred in one of the 27 radiologically inserted gastrostomy tubes (3.7%) compared to 14 of the 97 (14%) nonradiologically inserted gastrostomy tubes (P = .19), of which 12 were inserted endoscopically and two were inserted surgically. Of the 109 patients with successful tube conversion, jejunal tip malposition occurred at follow-up in 18 (16.5%). Of these, four patients developed aspiration pneumonia (22%), which contributed to patient death in two. The frequency of jejunal tip malposition was 3.8% (one of 26 patients) for radiologically placed gastrostomy tubes and 20% (17 of 83 patients) for nonradiologically placed gastrostomy tubes (P = .07). Combined, 32% of gastrostomy tubes placed nonradiologically resulted in either procedural failure or eventual jejunal tip malposition, compared to 7.4% of radiologically placed gastrostomy tubes (P = .01).
CONCLUSIONS - The frequency of procedural failure or eventual jejunal tip malposition with conversion of radiologically placed gastrostomy tubes to gastrojejunostomy tubes is significantly lower with radiologically placed gastrostomy tubes than with nonradiologically inserted gastrostomy tubes.
Copyright 2010 SIR. Published by Elsevier Inc. All rights reserved.
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15 MeSH Terms
Surgical removal of omental fat does not improve insulin sensitivity and cardiovascular risk factors in obese adults.
Fabbrini E, Tamboli RA, Magkos F, Marks-Shulman PA, Eckhauser AW, Richards WO, Klein S, Abumrad NN
(2010) Gastroenterology 139: 448-55
MeSH Terms: Adult, Blood Glucose, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Female, Gastric Bypass, Glucose Clamp Technique, Glucose Tolerance Test, Humans, Insulin, Insulin Resistance, Intra-Abdominal Fat, Laparoscopy, Lipectomy, Liver, Longitudinal Studies, Male, Middle Aged, Muscle, Skeletal, Obesity, Omentum, Risk Assessment, Risk Factors, Time Factors, Treatment Outcome
Show Abstract · Added May 27, 2014
BACKGROUND & AIMS - Visceral adipose tissue (VAT) is an important risk factor for the metabolic complications associated with obesity. Therefore, a reduction in VAT is considered an important target of obesity therapy. We evaluated whether reducing VAT mass by surgical removal of the omentum improves insulin sensitivity and metabolic function in obese patients.
METHODS - We conducted a 12-month randomized controlled trial to determine whether reducing VAT by omentectomy in 22 obese subjects increased their improvement following Roux-en-Y gastric bypass (RYGB) surgery in hepatic and skeletal muscle sensitivity to insulin study 1. Improvement was assessed by using the hyperinsulinemic-euglycemic clamp technique. We also performed a 3-month, longitudinal, single-arm study to determine whether laparoscopic omentectomy alone, in 7 obese subjects with type 2 diabetes mellitus (T2DM), improved insulin sensitivity study 2. Improvement was assessed by using the Frequently Sampled Intravenous Glucose Tolerance Test.
RESULTS - The greater omentum, which weighed 0.82 kg (95% confidence interval: 0.67-0.97), was removed from subjects who had omentectomy in both studies. In study 1, there was an approximate 2-fold increase in muscle insulin sensitivity (relative increase in glucose disposal during insulin infusion) and a 4-fold increase in hepatic insulin sensitivity 12 months after RYGB alone and RYGB plus omentectomy, compared with baseline values (P<.001). There were no significant differences between groups (P>.87) or group x time interactions (P>.36). In study 2, surgery had no effect on insulin sensitivity (P=.844) or use of diabetes medications.
CONCLUSIONS - These results demonstrate that decreasing VAT through omentectomy, alone or in combination with RYGB surgery, does not improve metabolic function in obese patients.
Copyright (c) 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
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25 MeSH Terms
Body composition and energy metabolism following Roux-en-Y gastric bypass surgery.
Tamboli RA, Hossain HA, Marks PA, Eckhauser AW, Rathmacher JA, Phillips SE, Buchowski MS, Chen KY, Abumrad NN
(2010) Obesity (Silver Spring) 18: 1718-24
MeSH Terms: Adipose Tissue, Adolescent, Adult, Aged, Body Composition, Body Fluid Compartments, Energy Metabolism, Female, Gastric Bypass, Humans, Longitudinal Studies, Male, Methylhistidines, Middle Aged, Muscle Proteins, Myofibrils, Obesity, Morbid, Radiography, Weight Loss, Young Adult
Show Abstract · Added December 10, 2013
Roux-en-Y gastric bypass (RYGB) surgery has become an accepted treatment for excessive obesity. We conducted a longitudinal study to assess regional body composition, muscle proteolysis, and energy expenditure before RYGB, and 6 and 12 months after RYGB. Whole-body and regional fat mass (FM) and lean mass (LM) were assessed via dual energy X-ray absorptiometry (DXA), and myofibrillar protein degradation was estimated by urinary 3-methylhistidine (3-MeH) in 29 subjects. Energy expenditure and substrate oxidation were also determined using a whole-room, indirect calorimeter in 12 of these subjects. LM loss constituted 27.8 +/- 10.2% of total weight loss achieved 12 months postoperatively, with the majority of LM loss (18 +/- 6% of initial LM) occurring in the first 6 months following RYGB. During this period, the trunk region contributed 66% of whole-body LM loss. LM loss occurred in the first 6 months after RYGB despite decreased muscle protein breakdown, as indicated by a decrease in 3-MeH concentrations and muscle fractional breakdown rates. Sleep energy expenditure (SEE) decreased from 2,092 +/- 342 kcal/d at baseline to 1,495 +/- 190 kcal/day at 6 months after RYGB (P < 0.0001). Changes in both LM and FM had an effect on the reduction in SEE (P < 0.001 and P = 0.005, respectively). These studies suggest that loss of LM after RYGB is significant and strategies to maintain LM after surgery should be explored.
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20 MeSH Terms
The importance of caloric restriction in the early improvements in insulin sensitivity after Roux-en-Y gastric bypass surgery.
Isbell JM, Tamboli RA, Hansen EN, Saliba J, Dunn JP, Phillips SE, Marks-Shulman PA, Abumrad NN
(2010) Diabetes Care 33: 1438-42
MeSH Terms: Adipokines, Adult, Blood Glucose, Caloric Restriction, Combined Modality Therapy, Eating, Fasting, Female, Gastric Bypass, Gastric Inhibitory Polypeptide, Glucagon-Like Peptide 1, Homeostasis, Humans, Insulin Resistance, Male, Middle Aged, Obesity, Morbid, Postoperative Period, Weight Loss
Show Abstract · Added May 27, 2014
OBJECTIVE - Many of the metabolic benefits of Roux-en-Y gastric bypass (RYGB) occur before weight loss. In this study we investigated the influence of caloric restriction on the improvements in the metabolic responses that occur within the 1st week after RYGB. RESEARCH METHODS AND DESIGN: A mixed meal was administered to nine subjects before and after RYGB (average 4 +/- 0.5 days) and to nine matched, obese subjects before and after 4 days of the post-RYGB diet.
RESULTS - Weight loss in both groups was minimal; the RYGB subjects lost 1.4 +/- 5.3 kg (P = 0.46) vs. 2.2 +/- 1.0 kg (P = 0.004) in the calorically restricted group. Insulin resistance (homeostasis model assessment of insulin resistance) improved with both RYGB (5.0 +/- 3.1 to 3.3 +/- 2.1; P = 0.03) and caloric restriction (4.8 +/- 4.1 to 3.6 +/- 4.1; P = 0.004). The insulin response to a mixed meal was blunted in both the RYGB and caloric restriction groups (113 +/- 67 to 65 +/- 33 and 85 +/- 59 to 65 +/- 56 nmol x l(-1) x min(-1), respectively; P < 0.05) without a change in the glucose response. Glucagon-like peptide 1 levels increased (9.2 +/- 8.6 to 12.2 +/- 5.5 pg x l(-1) x min(-1); P = 0.04) and peaked higher (45.2 +/- 37.3 to 84.8 +/- 33.0 pg/ml; P = 0.01) in response to a mixed meal after RYGB, but incretin responses were not altered after caloric restriction.
CONCLUSIONS - These data suggest that an improvement in insulin resistance in the 1st week after RYGB is primarily due to caloric restriction, and the enhanced incretin response after RYGB does not improve postprandial glucose homeostasis during this time.
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19 MeSH Terms
Roux-en-Y gastric bypass reverses renal glomerular but not tubular abnormalities in excessively obese diabetics.
Saliba J, Kasim NR, Tamboli RA, Isbell JM, Marks P, Feurer ID, Ikizler A, Abumrad NN
(2010) Surgery 147: 282-7
MeSH Terms: Adult, Body Mass Index, Creatinine, Cystatin C, Diabetes Mellitus, Type 2, Female, Gastric Bypass, Glomerular Filtration Rate, Humans, Kidney Function Tests, Kidney Glomerulus, Kidney Tubules, Male, Middle Aged, Obesity, Morbid
Show Abstract · Added May 27, 2014
BACKGROUND - Obesity and type 2 diabetes are associated with renal dysfunction, which improves after Roux-en-Y gastric bypass (RYGB). During a 12-month follow-up period, we studied prospectively the changes in glomerular and tubular functions that occurred in excessively obese diabetic and non diabetic subjects after RYGB.
METHODS - The cohort included 35 patients, 54% of whom had type 2 diabetes. Glomerular filtration rate (GFR) was estimated using creatinine clearance. Tubular function was studied by measuring the ratio of urinary cystatin C to urinary creatinine (UCC ratio).
RESULTS - Baseline renal parameters, anthropometric characteristics, and changes in body mass index after the surgical procedures were similar between the 2 cohorts. At 12 months after RYGB, creatinine clearance decreased 15% in diabetics (P = .02) and 21% in nondiabetics (P = .03). A change in GFR was seen earlier in the nondiabetics (-29% after 6 months; P = .003). The UCC ratio was increased at both 6- and 12-month follow-ups (P = .03 and .003, respectively) only in the diabetic group.
CONCLUSION - GFR was improved at 12 months after RYGB, with nondiabetics showing a greater propensity score. Tubular function remained unchanged in the nondiabetic subjects, but worsening occurred in the diabetic subjects. These results underscore the importance of reversal of excessive obesity before the onset of frank diabetes.
Copyright 2010 Mosby, Inc. All rights reserved.
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15 MeSH Terms