RYGB Surgery Research Articles

1996-P: Paternal Gastric Bypass Surgery Confers Protection from Metabolic Syndrome and Hepatic Steatosis in Offspring Mice

Bariatric surgery is increasingly recognized as a potent approach for obesity and T2D. While bariatric surgery in females yields variable effects on offspring, the impact of bariatric surgery in males on metabolism of their offspring is unknown. To determine whether paternal RYGB could induce intergenerational effects, male C57BL/6 mice with Roux-en-Y gastric bypass 5 months earlier (RYGB, n=4) or weight/age-matched controls (CON, n=5) were bred with healthy females of the same strain; 3 pregnancies were achieved by RYGB and 6 by CON males. Birth weight of offspring from RYGB or CON fathers did not differ. Seven offspring (2 litters) of RYGB fathers and 12 (2 litters) of CON fathers survived to weaning. On chow diet, male offspring of RYGB fathers reduced weight gain over time (p<0.05 vs. CON) but there was no significant difference in insulin sensitivity or glucose tolerance at 3 months of age. At 6 months of age, male offspring of RYGB fathers had significantly lower fasting glucose and improved oral glucose tolerance (17% lower AUC, p<0.05). When fed a 45% high-fat diet (HFD) for 15 weeks, RYGB offspring had significantly lower weight gain than control offspring, with lower body weight (37±5.7g vs. 51±1.1g), and reduced fat percentage (36±6.8 vs. 48±1.1%), in turn potentially linked to reduced food intake. Moreover, RYGB offspring had lower fasting glucose, improved insulin sensitivity (intraperitoneal insulin tolerance), and increased respiratory exchange ratio in fed state. In addition, HFD-fed RYGB offspring had dramatic improvement in hepatic steatosis, with 70% of RYGB offspring having no steatosis, as compared with 100% of CON offspring with severe steatosis (p<0.0001). In conclusion, RYGB surgery in fathers prior to breeding can provide protection against metabolic syndrome and hepatic steatosis in offspring, and suggests that interventions to improve the health of fathers could interrupt intergenerational cycles of obesity and diabetes risk. Disclosure Y. Yuchi: None. Z. Hao: None. T. Takagi: None. H. Berthoud: None. M.E. Patti: Consultant; Self; Eiger BioPharmaceuticals. Research Support; Self; Dexcom, Inc., Janssen Pharmaceuticals, Inc., MedImmune, Xeris Pharmaceuticals, Inc. Funding The Medical Foundation; National Institutes of Health (DK047348)

Combined loss of GLP-1R and Y2R does not alter progression of high-fat diet-induced obesity or response to RYGB surgery in mice

ObjectiveUnderstanding the mechanisms underlying the remarkable beneficial effects of gastric bypass surgery is important for the development of non-surgical therapies or less invasive surgeries in the fight against obesity and metabolic disease. Although the intestinal L-cell hormones glucagon-like peptide-1 (GLP-1) and peptide tyrosine–tyrosine (PYY) have attracted the most attention, direct tests in humans and rodents with pharmacological blockade or genetic deletion of either the GLP1-receptor (GLP1R) or the Y2-receptor (Y2R) were unable to confirm their critical roles in the beneficial effects gastric bypass surgery on body weight and glucose homeostasis. However, new awareness of the power of combinatorial therapies in the treatment of metabolic disease would suggest that combined blockade of more than one signaling pathway may be necessary to reverse the beneficial effects of bariatric surgery. MethodsThe metabolic effects of high-fat diet and the ability of Roux-en-Y gastric bypass surgery to lower food intake and body weight, as well as improve glucose handling, was tested in GLP1R and Y2R-double knockout (GLP1RKO/Y2RKO) and C57BL6J wildtype (WT) mice. ResultsGLP1RKO/Y2RKO and WT mice responded similarly for up to 20 weeks on high-fat diet and 16 weeks after RYGB. There were no significant differences in loss of body and liver weight, fat mass, reduced food intake, relative increase in energy expenditure, improved fasting insulin, glucose tolerance, and insulin tolerance between WT and GLP1RKO/Y2RKO mice after RYGB. ConclusionsCombined loss of GLP1R and Y2R-signaling was not able to negate or attenuate the beneficial effects of RYGB on body weight and glucose homeostasis in mice, suggesting that a larger number of signaling pathways is involved or that the critical pathway has not yet been identified.

255 Recurrent Oxalosis Post Kidney Transplantation with Prior RYGB Surgery

255 Recurrent Oxalosis Post Kidney Transplantation with Prior RYGB Surgery

RYGB increases the satiating effect of intrajejunal lipid infusions in female rats

We used a novel rat model to investigate the physiological bases of early satiation after Roux-en-Y gastric bypass surgery (RYGB). Female rats were subjected to RYGB or sham surgery. Chronic infusion catheters were placed in the Roux limb of RYGB rats and the corresponding anatomical locus of the jejuna of sham-RYGB rats. Rats were also ovariectomized and chronically treated with either estradiol (E2; 2 μg each 4th day SC) or the oil vehicle. Testing was begun 10–12 wk after surgery. Intrajejunal lipid infusions (10 min, 4.4 mL, 8.8 kcal) were performed just before test meals of a low-energy artificially sweetened gel diet (0.1 kcal/g) that RYGB rats ingest avidly. Intrajejunal lipid infusions reduced test-meal size more in RYGB rats than sham-operated rats, indicating that, at least after prolonged adaptation to surgery, the satiating actions of lipids acting intra- or post-jejunally are increased by RYGB and that accelerated meal appearance in the intestines after RYGB is not necessary for this effect. The satiating effects of intrajejunal lipid infusions were similar in E2-and oil-treated rats, suggesting that the effect was not dependent on an activational effect of estrogens. In a second experiment, pretreatment with the cholecystokinin A-receptor antagonist devazepide reduced the satiating effect of intrajejunal lipid infusions in E2-treated RYGB rats. Although these data are preliminary due to the smaller numbers of rats than in the first experiment, they suggest that cholecystokinin-mediated jejunal satiation contributes to early satiation after RYGB in ovariectomized rats with peri-ovulatory levels of estradiol. The results of these experiments may be relevant to understanding RYGB outcome in pre- and postmenopausal women.

Roux-en-Y gastric bypass surgery normalizes dopamine D1, D2, and DAT levels.

Roux-en-Y gastric bypass surgery (RYGB) is one of the most effective treatments for morbid obesity. However, increased substance abuse following RYGB has been observed clinically. This study examined the effects of RYGB on the dopamine system to elucidate these observed changes in reward-related behavior. Rats were assigned to four groups: normal diet with sham surgery, ad libitum high fat (HF) diet with sham surgery, restricted HF diet with sham surgery, and HF diet with RYGB surgery. Following surgeries, rats were kept on their respective diets for 9 weeks before they were sacrificed. [3 H]SCH 23390, [3 H]Spiperone, and [3 H]WIN35 428 autoradiography was performed to quantify the effects of diet and RYGB surgery on dopamine type 1-like receptor (D1R)-like, dopamine type 2-like receptor (D2R)-like, and dopamine transporter (DAT) binding. Rats on a chronic HF diet became obese with reduced D1R-like binding within the ventrolateral striatum and the nucleus accumbens core, reduced D2R-like binding in all areas of the striatum and nucleus accumbens core and shell, and reduced DAT binding in the dorsomedial striatum. Restricted HF diet rats showed similar reductions in D1R-like and D2-R-like binding as the obese rats, and reduced DAT binding within all areas of the striatum. Both RYGB and restricted HF diet rats showed similar weight reductions, with RYGB rats showing no difference in binding compared to controls. The observed changes in binding between non-treated obese rats and RYGB rats demonstrates that HF dietary effects on the dopamine system were reversed by RYGB.

The Family Coriobacteriaceae Is a Potential Contributor to the Beneficial Effects of Roux-en-Y Gastric Bypass on Type 2 Diabetes

Background: Changes in gut microbiota induced by bariatric surgery have been associated with metabolic benefits. Objectives: Our aim was to identify specific gut microbiota that may contribute to the improvement of type 2 diabetes (T2D) after RYGB.Setting: Laboratories of Shanghai Diabetes Institute and Shanghai Sixth People’s Hospital. Methods: Diabetic rats induced via a high-fat diet and low-dose streptozotocin administration were randomized to RYGB or sham surgery (SHAM), and stool samples were collected at baseline and at postoperative week 8. The faecal microbiota was profiled using 16S ribosomal RNA (rRNA) gene sequencing. Additionally, we performed a case-control study of the gut microbial community profiles of T2DM patients compared to those of healthy individuals (CONT) via 16S rRNA gene sequencing of mucosal-luminal interface samples collected from the ascending colon during colonoscopy. Results: RYGB significantly reduced the body weight and improved glucose tolerance and insulin sensitivity in diabetic rats. Principal coordinate analysis showed that RYGB caused marked alterations in the gut microbiota. The RYGB group was postoperatively enriched for Bacteroidetes, Proteobacteria, Fusobacteria and Actinobacteria; whereas the SHAM group was enriched for Firmicutes and Verrucomicrobia. Based on the gut microbial patterns in the T2D patients, we found that the family Coriobacteriaceae within Actinobacteria might contribute to the beneficial effects of RYGB on T2D. Conclusions: RYGB significantly improves glucose metabolism and alters the gut microbiota. Moreover, the family Coriobacteriaceae may partly mediate the beneficial effects of RYGB on T2D and thus possibly contribute to the development of novel bacteria-based therapeutic approaches. Disclosure C. Hu: None. W. Jia: None. H. Liu: None.

Assessment of the Dynamic Insulin Secretion and Sensitivity Test (DISST) Pre and Post Gastric bypass Surgery.

To compare the dynamic insulin secretion and sensitivity test (DISST) with the euglycaemic clamp in individuals undergoing open Roux-en-Y gastric bypass (RYGB) surgery prior-to and one month after surgery. Insulin sensitivity in individuals with obesity undergoing RYGB was studied with DISST and a euglycaemic hyperinsulinaemic clamp. Eleven participants, including nine females, mean(SD) age 51.2 (12.1) yrs, with a preoperative BMI of 48.7(9.5)kg/m2 were studied. Weight reduced from a mean (SD) of 133.8 (29.8) kg to 123.8 (28.9) kg post-surgery (p<0.001). The mean (SD) insulin sensitivity index (ISI-DISST) was 3.07×10-4 (2.18) L.pmol-1.min-1 preoperatively and 2.36 ×10-4 (0.78)L.pmol-1.min-1 postoperatively (p=0.37). The mean(SD) clamp ISI was 2.14 ×10-2 (1.80) mg.L.kg-1.min-1.pmol-1 and 2.00×10-2.(0.76) mg.L.kg-1.min-1.pmol-1 postoperatively (p=0.86). Correlation between ISI-DISST and ISI-Clamp preoperatively was r=0.81(95%CI 0.37-0.95) and post-operatively r=0.47(95%CI 0-0.88). Bland-Altman analysis demonstrates systematic bias between the two tests, where DISST underestimated insulin sensitivity compared with the clamp by 0.96×10-2.mg.L.kg-1.min-1.pmol-1 (95%CI -2.24 to 0.32). There was a strong correlation between DISST and the clamp preoperatively and DISST can be used to estimate insulin sensitivity in individuals with morbid obesity. After RYGB surgery, DISST had a weaker correlation with the clamp suggesting the fundamental physiological determinants of insulin sensitivity being measured by each method change in different ways with changes in glucose homeostasis following RYGB surgery.

Lipids as potential contributors to the beneficial effects of Roux‐en‐Y gastric bypass surgery (RYGB)

RYGB is still the most effective treatment of obesity and its comorbidities, but the signaling molecules and mechanisms that mediate the beneficial effects of RYGB are largely unknown. One of the classes of molecules that could be involved are gut‐derived endogenous lipids. We therefore investigated profiles of potential lipid mediators locally in the gut. We non‐occlusively cannulated the mesenteric lymph duct of diet‐induced obese (DIO), insulin‐resistant RYGB or sham‐operated rats and collected lymph samples in relation to spontaneous meals for subsequent mass spectrometry analysis of the intestinal lymphatic lipidome from all animals prior to and 5, 10 and 21 days after the surgery. A multivariate analysis revealed two separate clusters for the lipidomes of the animals of the two surgical groups. Unlike sham‐surgery, RYGB surgery changed the levels of &gt;150 lipids compared to pre‐surgical levels. TG were mostly decreased after RYGB, presumably reflecting the reduced food intake. Some lipids, however, were increased in intestinal lymph after RYGB. Especially those reported to be decreased in obesity (e.g., lysophosphatidylcholine [LPC] 20:1 or phosphatidylcholine [PC] 32:0) were upregulated about two‐fold 21 days after the RYGB surgery. This might be related to the decreased body weight rather than being a direct surgery effect. Some lipids, however, (e.g., PC 40:7, phosphatidylethanolamines [PE] 40:6, sphingomyelins [SM] 18:0) were upregulated in the RYGB group already 5 days after surgery, long before their body weight was significantly decreased compared to sham‐operated controls. Notably, there was a strong positive correlation between RYGB surgery and longer chain length in particular for TG, diacylglycerols [DG], PE, and SM. Moreover, TG, DG and phosphatidylinositols showed a positive correlation between RYGB surgery and an increased frequency of double bonds. Whether these changes are cause or consequence of an improvement of enterocyte structure and function, and whether they contribute to the reported improvement of the various comorbidities requires further investigation.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Inhibition of Vascular c-Jun N-Terminal Kinase 2 Improves Obesity-Induced Endothelial Dysfunction After Roux-en-Y Gastric Bypass.

BackgroundRoux‐en‐Y gastric bypass (RYGB) reduces obesity‐associated comorbidities and cardiovascular mortality. RYGB improves endothelial dysfunction, reducing c‐Jun N‐terminal kinase (JNK) vascular phosphorylation. JNK activation links obesity with insulin resistance and endothelial dysfunction. Herein, we examined whether JNK1 or JNK2 mediates obesity‐induced endothelial dysfunction and if pharmacological JNK inhibition can mimic RYGB vascular benefits.Methods and ResultsAfter 7 weeks of a high‐fat high‐cholesterol diet, obese rats underwent RYGB or sham surgery; sham–operated ad libitum–fed rats received, for 8 days, either the control peptide D‐TAT or the JNK peptide inhibitor D‐JNKi‐1 (20 mg/kg per day subcutaneous). JNK peptide inhibitor D‐JNKi‐1 treatment improved endothelial vasorelaxation in response to insulin and glucagon‐like peptide‐1, as observed after RYGB. Obesity increased aortic phosphorylation of JNK2, but not of JNK1. RYGB and JNK peptide inhibitor D‐JNKi‐1 treatment blunted aortic JNK2 phosphorylation via activation of glucagon‐like peptide‐1–mediated signaling. The inhibitory phosphorylation of insulin receptor substrate‐1 was reduced, whereas the protein kinase B/endothelial NO synthase pathway was increased and oxidative stress was decreased, resulting in improved vascular NO bioavailability.ConclusionsDecreased aortic JNK2 phosphorylation after RYGB rapidly improves obesity‐induced endothelial dysfunction. Pharmacological JNK inhibition mimics the endothelial protective effects of RYGB. These findings highlight the therapeutic potential of novel strategies targeting vascular JNK2 against the severe cardiovascular disease associated with obesity.

Roux-en-Y gastric bypass reduces plasma cholesterol in diet-induced obese mice by affecting trans-intestinal cholesterol excretion and intestinal cholesterol absorption.

Bariatric surgery appears as the most efficient therapeutic alternative in morbidly obese patients. In addition to its efficiency to decrease body weight, it also improves metabolic complications associated to morbid obesity, including dyslipidemia. Although the cholesterol-lowering effect varies with the bariatric procedures, the underlying molecular mechanisms remain poorly defined. This study aims to assess the consequence of both restrictive (sleeve gastrectomy; SG) and malabsorptive (Roux-en-Y gastric bypass; RYGB) procedures on cholesterol metabolism in mice. Ten-week-old C57BL6/J males were fed with a high-fat diet for 8-14 weeks before sleeve or RYGB surgery. SG has a modest and transient effect on plasma cholesterol levels, linked to a reduction in food intake. In contrast, modified RYGB led to a sustained ≈35% reduction in plasma cholesterol concentrations with a drastic increase in fecal cholesterol output. Mechanistically, RYGB exerts a synergystic effect on cholesterol metabolism by inducing the trans-intestinal cholesterol efflux and reducing the intestinal cholesterol absorption. In mice, RYGB, but not sleeve, strongly favors plasma cholesterol elimination by concomitantly increasing trans-intestinal cholesterol excretion and by decreasing intestinal cholesterol absorption. Our models open new perspective for deciphering the hypocholesterolemic effects of bariatric procedures.

Performance of the DiaRem Score for Predicting Diabetes Remission in Two Health Systems Following Bariatric Surgery Procedures in Hispanic and non-Hispanic White Patients.

The objective of this study was to determine whether the DiaRem, a score that predicts type 2 diabetes (T2D) remission following roux-en-y gastric bariatric surgery (RYGB), also predicts remission following laparoscopic adjustable gastric banding (LAGB) and laparoscopic sleeve gastrectomy (LSG) in white and Hispanic patients. While bariatric surgery is highly effective in reversing insulin resistance, there are patients for whom surgery will not lead to remission. To date, there is no score for predicting remission following LAGB or LSG surgery. Additionally, there is little known about how to predict whether Hispanic patients will experience remission. We conducted a retrospective cohort study of white and Hispanic patients with T2D who received bariatric surgery. There were 361 white and 130 Hispanic patients among whom 328 had RYGB surgery, 107 had LSG surgery, and 56 had LAGB surgery. We used age, diabetes treatment, and hemoglobin A1c to calculate DiaRem scores. Mann-Whitney U test was used to determine the association between DiaRem scores and remission. Area under the receiver operant curve (AUC) was used to assess the ability of the DiaRem to discriminate between patients who did and did not remit. The DiaRem was associated with partial remission in all surgery types for white and Hispanic patients (Mann-Whitney, p<0.001). The DiaRem had moderate to high discriminant ability (AUC>0.70) for all surgical and racial/ethnic groups. The DiaRem distinguishes between patients likely and unlikely to experience remission, informing expectations of patients making T2D treatment decisions.

Differential acute and chronic responses in insulin action in cultured myotubes following from nondiabetic severely obese humans following gastric bypass surgery

BackgroundRoux-en-Y gastric bypass (RYGB) surgery has been shown to induce positive metabolic adaptations for individuals with severe obesity (body mass index ≥40 kg/m2), including improved peripheral insulin action. Although a major site of insulin action, the time course changes in skeletal muscle glucose metabolism following RYGB is unclear. ObjectivesTo investigate the acute and chronic effects of RYGB surgery on insulin-stimulated glucose metabolism in cultured human primary myotubes derived from nondiabetic severely obese humans. SettingEast Carolina University Bariatric Surgery Center and East Carolina Diabetes and Obesity Institute. MethodsPrimary human skeletal muscle cells were isolated from biopsies obtained from 8 women with severe obesity before, 1 month, and 7 months following RYGB surgery. Glucose metabolism, glycogen content, and insulin signal transduction were determined in differentiated myotubes. ResultsInsulin-stimulated glycogen synthesis and glucose oxidation increased in human myotubes derived from patients with severe obesity at both 1 and 7 months post-RYGB. However, there were no alterations indicative of enhanced insulin signal transduction. At 1 month post-RYGB, muscle glycogen levels were lower (-23%) and phosphorylation of acetyl CoA carboxylase 2 (ACC2) was elevated (+16%); both returned to presurgery levels at 7 months after RYGB in myotubes derived from patients. At 7 months post-RYGB, there was an increase in peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) protein content (+54%). ConclusionThese data indicate that insulin action intrinsically improves in cultured human primary myotubes derived from nondiabetic severely obese patients following RYGB surgery; however, the cellular alterations involved appear to consist of distinct acute and chronic components.

Effect of Gastric By‐pass on Dietary Protein Bioavailability and Protein Anabolism in Rats

IntroductionBariatric surgery is an efficient treatment of massive obesity but it can trigger nutritional deficiencies, especially regarding vitamins and proteins. Protein wasting may be observed although there are large prevalence variations in the literature. Additionally to a low protein intake, protein malabsorption logically appears as a risk factor of protein wasting. However, there is little data on protein digestion after bariatric surgery. Our study aimed to assess the effect of gastric‐bypass (RYGB) on dietary protein bioavailability and protein status in rats.MethodsRats were fed for 3 months an obesogenic diet. Eighteen rats underwent RYGB surgery (survival: n=9) and 10 Sham (survival: n=10) served as control that were pair‐fed. For 15 d post‐surgery, dietary intake, weight and body composition were measured. After 15 d, rats were given a test meal containing 15N labeled proteins. They were sacrificed 6 h after the meal and dietary proteins were quantified in gastrointestinal segments (stomach, duodenum, jejunum, ileum, caecum and colon) by elemental analyzer coupled to isotope ratio mass spectrometer. Small intestine morphology was studied by histology. The protein Fractional Synthesis Rate (FSR) was measured in the liver, kidney, muscle and skin using a 13C valine flooding dose before sacrifice. Results (means ± SEM) were analyzed using a t test (P&lt;0.05).ResultsCompared to baseline, RYGB decreased dietary intake by 49%. Despite pair‐feeding, weight loss was higher in RYGB than in Sham (14±2 % vs 7±0.8 %, P= 0.002), as well as fat mass loss (33±5 % vs 20±1 %, P=0.03). Lean mass loss was 7±1.5 %. in both groups. Six hours after the meal test, there was more dietary nitrogen in the caecum of Sham than RYGB but no difference was detected in other intestinal segments. Real protein digestibility was lower in Sham than RYGB (93.1±0.6 % vs 95.2±0.7%, P=0.03). Histology revealed a hypertrophy of jejunum mucosa in RYGB. The FSR of kidney protein was strongly decreased (P&lt;0.001) in RYGB (72.2±3.2 %/j) compared to sham (98.4±3.3 %/j). Protein anabolism was similar between groups in other tissues.ConclusionWe showed that dietary protein bioavailability was paradoxically improved in RYGB, an effect that can be attributed to the jejunum mucosa hypertrophy. We also revealed that RYGB markedly lowered protein anabolism in the kidney. It will be interesting to identify which protein are involved in this effect.

The effect of close postoperative follow-up on co-morbidity improvement after bariatric surgery

BackgroundPatients undergoing gastric bypass (RYGB) surgery require follow-up for efficacy assessment, early detection of postoperative complications, and also for management of co-morbid conditions. Recent literature shows support for improved long-term weight loss with close patient follow-up. However, attrition rates after RYGB have been reported as high as 50%. ObjectiveThe objective of this study was to assess the relationship between complete follow-up and improvement or remission of co-morbid conditions at 12 months after surgery. SettingUniversity Hospital, United States. MethodsUsing the Bariatric Outcomes Longitudinal Database (BOLD) data set, patients with 12-month follow-up after RYGB were identified. Patients with complete follow-up were compared with patients who had missed either or both of their 3- and 6-month visits. Improvement and remission of type 2 diabetes, hypertension, and dyslipidemia were evaluated at 12-month postoperatively. Results46,381 patients (30.6% of all RYGB patients) were identified that had follow-up with minimum 12-month data. Complete follow-up was recorded for 75.6% of this group with 12-month data. Of the 18,629 patients with type 2 diabetes at baseline, 13,498 (72.4%) and 11,287 (60.6%) had improvement and remission, respectively, at 12 months. Improvement in hypertension and dyslipidemia was noted in 17,808 (62.8%) and 11,602 (55.2%) of patients, while 13,024 (45.9%) and 9119 (43.4%) had hypertension and dyslipidemia remission, respectively. After adjusting for baseline characteristics, complete follow-up in the first year after RYGB was independently associated with a higher rate of improvement or remission of co-morbid conditions. ConclusionComplete postoperative follow-up resulted in a higher rate of co-morbidity improvement and remission compared with incomplete postoperative care. Patients and practices should strive to achieve complete and long-term follow-up after RYGB surgery.

Patients' Preoperative Estimate of Target Weight and Actual Outcome after Bariatric Surgery.

Evidence about the impact of psychological factors on weight loss after bariatric surgery is scarce. This study explores whether patients' preoperative estimate of target weight influences actual weight loss for different types of bariatric procedures. Patients eligible for bariatric surgery were instructed twice on how to calculate their expected target weight. They were divided into three groups based on their percentage excess weight loss (%EWL) and percentage total body weight loss (%TBWL). Weight loss 12 and 24months after surgery was analyzed for each group and per type of surgery. Six hundred fifty-six patients participated in this study. Types of surgery performed were the Roux-en-Y gastric bypass (RYGB, 75%), sleeve gastrectomy (SG, 8.1%), REDO-RYGB (12.5%), and laparoscopic adjustable gastric banding (LAGB, 4.4%). Data of 622 and 410 patients were available for analysis at 12 and 24months, respectively. Surprisingly, 415 patients (63.3%) overestimated their expected weight loss as opposed to our calculation, based on our own historic data. One hundred thirty-four patients (20.4%) estimated their weight loss correctly and 107 patients (16.3%) underestimated their weight loss. There was a significant higher %EWL 12months after RYGB surgery for patients who overestimated their weight loss compared to those who estimated their weight loss correctly (p=0.001). After 24months and for other types of procedures, no statistically significant differences were found between the three groups. Despite instructions on how to calculate target weight, the majority of patients overestimated their weight loss. Actual %EWL 12months after RYGB surgery might be influenced by setting a low target weight.

Decreased Cardiovascular Risk after Roux-en-Y Gastric Bypass Surgery in Chinese Diabetic Patients with Obesity.

Background The influence of bariatric surgery on cardiovascular risks in Chinese diabetic patients remains unclear. Here, we aimed to explore the impact of Roux-en-Y gastric bypass surgery (RYGB) on cardiovascular risks in Chinese diabetic patients with obesity. Methods Twenty Chinese patients with T2DM and obesity undergoing RYGB surgery were included in this study. Cardiovascular risk factors were measured before and 18 months after surgery. A 10-year cardiovascular risk was calculated by the UKPDS risk engine. Linear regression analysis was performed on CHD risk, stroke risk, and baseline metabolic parameters. Results The complete remission rate of diabetes was 90% after RYGB surgery, with significant improvements in blood pressure, BMI, glucose, and lipid metabolism (P < 0.05). The 10-year cardiovascular risk of coronary heart disease reduced from 13.05% to 3.81% (P = 0.001) and the 10-year risk of stroke reduced from 19.66% to 14.22% (P = 0.002). In subgroup analysis, Chinese diabetic patients who were women, <45 years old, with BMI < 35 kg/m2, and DM duration > 5 years, using noninsulin therapy presented more obvious improvements in the 10-year cardiovascular risk after RYGB surgery. WHR, age, LDL-C, and HbA1c were the most important factors influencing CHD or stroke risk after RYGB surgery (P < 0.01). Conclusion RYGB surgery is an effective treatment to reduce cardiovascular risk in Chinese diabetic patients with obesity.

Roux-en-Y gastric bypass surgery is effective in fibroblast growth factor-21 deficient mice

ObjectiveThe mechanisms by which bariatric surgeries so effectively and lastingly reduce body weight and normalize metabolic dysfunction are not well understood. Fibroblast growth fator-21 (FGF21) is a key regulator of metabolism and is currently considered for treatment of obesity. Although elevated by acute food deprivation, it is downregulated after weight loss induced by chronic calorie restriction but not after Roux-en-Y gastric bypass surgery. Therefore, the goal of the present study was to assess the role of FGF21-signaling in the beneficial effects of Roux-en-Y gastric bypass surgery (RYGB). MethodsHigh-fat diet-induced obese FGF21-deficient (FGF21−/−) and wildtype (WT) mice were subjected to RYGB, sham surgery, or caloric restriction to match body weight of RYGB mice. Body weight, body composition, food intake, energy expenditure, glucose tolerance, and insulin sensitivity, as well as plasma levels and hepatic mRNA expression of FGF21 were measured. ResultsHepatic expression and plasma levels of FGF21 are higher after RYGB compared with similar weight loss induced by caloric restriction, suggesting that elevated FGF21 might play a role in preventing increased hunger and weight regain after RYGB. However, although the body weight differential between RYGB and sham surgery was significantly reduced in FGF21−/− mice, RYGB induced similarly sustained body weight and fat mass loss, initial reduction of food intake, increased energy expenditure, and improvements in glycemic control in FGF21−/− and WT mice. ConclusionsFGF21 signaling is not a critical single factor for the beneficial metabolic effects of RYGB. This may open up the possibility to use FGF21 as adjuvant therapy in patients with ineffective bariatric surgeries.

Energy Metabolic Adaptation and Cardiometabolic Improvements One Year After Gastric Bypass, Sleeve Gastrectomy, and Gastric Band.

It is not known whether the magnitude of metabolic adaptation, a greater than expected drop in energy expenditure, depends on the type of bariatric surgery and is associated with cardiometabolic improvements. To compare changes in energy expenditure (metabolic chamber) and circulating cardiometabolic markers 8 weeks and 1 year after Roux-en-y bypass (RYGB), sleeve gastrectomy (SG), laparoscopic adjustable gastric band (LAGB), or a low-calorie diet (LCD). Design, Setting, Participants, and Intervention: This was a parallel-arm, prospective observational study of 30 individuals (27 females; mean age, 46 ± 2 years; body mass index, 47.2 ± 1.5 kg/m2) either self-selecting bariatric surgery (five RYGB, nine SG, seven LAGB) or on a LCD (n = 9) intervention (800 kcal/d for 8 weeks, followed by weight maintenance). After 1 year, the RYGB and SG groups had similar degrees of body weight loss (33-36%), whereas the LAGB and LCD groups had 16 and 4% weight loss, respectively. After adjusting for changes in body composition, 24-hour energy expenditure was significantly decreased in all treatment groups at 8 weeks (-254 to -82 kcal/d), a drop that only persisted in RYGB (-124 ± 42 kcal/d; P = .002) and SG (-155 ± 118 kcal/d; P = .02) groups at 1 year. The degree of metabolic adaptation (24-hour and sleeping energy expenditure) was not significantly different between the treatment groups at either time-point. Plasma high-density lipoprotein and total and high molecular weight adiponectin were increased, and triglycerides and high-sensitivity C-reactive protein levels were reduced 1 year after RYGB or SG. Metabolic adaptation of approximately 150 kcal/d occurs after RYGB and SG surgery. Future studies are required to examine whether these effects remain beyond 1 year.

Systemic intraoperative lidocaine infusion for postoperative pain management in obese patients: A randomized, placebo controlled pilot study

Background: Systemic intraoperative lidocaine has been seen to decrease postoperative pain following abdominal surgery, butfew studies have examined its use in morbidly obese patients. Objective: We sought to evaluate the safety and effects of intravenous lidocaine in obese patients undergoing laparoscopicRoux-en-Y gastric bypass (RYGB) surgery. Methods: Setting: University-affiliated, private hospital, United States. In this preliminary prospective, double-blinded, andplacebo-controlled safety study, we enrolled 21 patients and 20 completed the study. Ten patients were randomly assigned to thestudy group and received a continuous infusion of lidocaine intravenously from induction of general anesthesia until the endof the operation. Ten other patients were assigned to the control group and received a dextrose placebo intravenously over thesame time period. Subjects were followed for 24 hours postoperatively. The primary endpoint was the presence of symptoms oflidocaine toxicity at 1 hour postoperatively. Exploratory outcomes were adverse events, visual analog scale (VAS) pain scores,opioid consumption, time to first passage of flatus and bowel movement, and length of hospital stay. Results: No significant differences were seen between groups for overt signs of lidocaine toxicity or adverse events, opioidconsumption, postoperative pain scores, time to first passage of flatus or first bowel movement, or length of hospital. We identifieda trend towards less opioid consumption in patients receiving lidocaine. We were underpowered to detect statistical differencesdue to our pilot study design; addressing safety as the primary outcome measure as opposed to efficacy. Conclusions: In this study, intravenous lidocaine in RYGB surgery was found to be safe without differences in postoperativepain or adverse effects.

The role of obestatin in Roux-en-Y gastric bypass surgery in the obese, type 2 diabetes Zucker rat

AimsRoux-en-Y gastric bypass (RYGB) is a novel therapy for diabetes and the exact mechanisms of this procedure remain unclear. Obestatin is an important gut hormone. We aimed to explore the role of obestatin in the therapeutic mechanism of RYGB. MethodsTwenty obese Zucker rats and twenty Wistar rats were randomly assigned to two groups: RYGB and sham surgery. We evaluated plasma obestatin and insulin levels pre- and post-RYGB. Additionally, obestatin expression levels in the gastrointestinal tract were assessed using immunohistochemical staining. ResultsIn Zucker rats, plasma obestatin and insulin levels gradually increased after RYGB. At post-operation week 7, plasma levels of obestatin were higher in the RYGB group than the sham operation group, and fasting plasma insulin levels were significantly increased the in RYGB group compared with the sham operation group. Furthermore, we observed a positive relationship between obestatin and insulin plasma levels. Among 10 zucker rats, high expression of obestatin was only seen in the jejunum of 2 rats before the operation; however, high expression of obestatin was seen in the Roux limb of 8 rats and in the ileum of 7 rats after RYGB. The expression of obestatin was significantly higher in the intestine in the RYGB group than the sham operation group postoperatively. ConclusionsWe propose that obestatin maybe a potential mediator to improve glucose homeostasis after RYGB. The increase of obestatin secretion may be an important mechanism through which RYGB alleviates obesity and type 2 diabetes mellitus.