LEAP2 changes with body mass and food intake in humans and mice

Acyl-ghrelin administration increases food intake, body weight, and blood glucose. In contrast, mice lacking ghrelin or ghrelin receptors (GHSRs) exhibit life-threatening hypoglycemia during starvation-like conditions but do not consistently exhibit overt metabolic phenotypes when given ad libitum food access. These results, and findings of ghrelin resistance in obese states, imply nutritional state-dependence of ghrelin’s metabolic actions. Here, we hypothesized that LEAP2 (liver enriched antimicrobial peptide-2), a recently-characterized endogenous GHSR antagonist, blunts ghrelin action during obese states and post-prandially. To test this hypothesis, we determined changes in plasma LEAP2 and acyl-ghrelin due to fasting, eating, obesity, Roux-en-Y gastric bypass (RYGB), vertical sleeve gastrectomy (VSG), oral glucose administration, and type 1 diabetes mellitus (T1DM) using humans and/or mice. Our results suggest that plasma LEAP2 is regulated by metabolic status: its levels increase with body mass and blood glucose, and decrease with fasting, RYGB, and in post-prandial states following VSG. These changes were mostly opposite to those of acyl-ghrelin. Furthermore, using electrophysiology, we showed that LEAP2 both hyperpolarizes and prevents acyl-ghrelin from activating arcuate NPY neurons. We predict that the plasma LEAP2:acyl-ghrelin molar ratio may be a key determinant modulating acyl-ghrelin activity in response to body mass, feeding status, and blood glucose

How to train surgical residents to perform laparoscopic roux-en-Y gastric bypass safely

Background As a result of increasing numbers of patients with morbid obesity there is a worldwide demand for bariatric surgeons. The Roux-en-Y gastric bypass, nowadays performed mostly laparoscopically (LRYGB), has been proven to be a highly effective surgical treatment for morbid obesity. This procedure is technically demanding and requires a long learning curve. Little is known about implementing these demanding techniques in the training of the surgical resident. The aim of this study was to evaluate the safety and feasibility of the introduction of LRYGB into the training of surgical residents. Methods All patients who underwent LRYGB between March 2006 and July 2010 were retrospectively analyzed. The procedure was performed by a surgical resident under strict supervision of a bariatric surgeon (group I) or by a bariatric surgeon (group II). The primary end point was the occurrence of complications. Secondary end points included operative time, days of hospitalization, rate of readmission, and reappearance in the emergency department (ED) within 30 days. Results A total of 409 patients were found eligible for inclusion in the study: 83 patients in group I and 326 in group II. There was a significant difference in operating time (129 min in group I vs. 116 min in group II; p<0.001) and days of hospitalization. Postoperative complication rate, reappearance in the ED, and rate of readmission did not differ between the two groups. Conclusions Our data suggest that under stringent supervision and with sufficient laparoscopic practice, implementation of LRYGB as part of surgical training is safe and results in only a slightly longer operating time. Complication rates, days of hospitalization, and the rates of readmission and reappearance in the ED within 30 days were similar between the both groups. These results should be interpreted by remembering that all procedures in group I were performed in a training environment so occasional intervention by a bariatric surgeon, when necessary, was inevitable

Metabolic syndrome remission after Roux-en-Y gastric bypass or sleeve gastrectomy

Ibrahim Nassour,1 Jaime P Almandoz,2 Beverley Adams-Huet,3,4 Sachin Kukreja,5 Nancy Puzziferri1,5 1Department of Surgery, 2Department of Internal Medicine, Division of Endocrinology, 3Department of Clinical Sciences, 4Department of Internal Medicine, University of Texas Southwestern Medical Center, 5Department of Surgery, Veterans Affairs North Texas Health Care System, Dallas, TX, USA Background: Bariatric surgery is known to decrease weight and the prevalence of comorbidities, but there is little evidence on the differential effect of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on the remission of the aggregate outcome, metabolic syndrome, 4 years after surgery. The purpose of this study was to determine the effectiveness of RYGB and SG on metabolic syndrome in veterans. Methods: We retrospectively reviewed consecutive patients who underwent SG and RYGB at the Dallas Veterans Affairs Medical Center from 2003 to 2012. We determined the effect of both the operations on the remission of metabolic syndrome, its individual components, and medium-term morbidity and mortality. A sensitivity analysis was performed using propensity matching.Results: A total of 266 patients were identified (159 RYGB and 107 SG) with 96% follow-up after 4 years. The mean age of the cohort was 51.4 years; the majority of patients were male (59%) and Caucasian (69%). RYGB patients had a greater mean body mass index and were more likely to have hypertension or hypertriglyceridemia. RYGB was associated with a similar metabolic syndrome remission to SG (37.6% vs 26.8%; P=0.09). The percentage of weight loss was 26.5% after RYGB and 10.8% after SG at 4 years post operation (P&lt;0.01). Predictors of metabolic syndrome persistence were male gender, type 2 diabetes, and low high-density lipoprotein. While both the operations were associated with similar mortality (RYGB 4.4%, SG 2.8%; P=0.74), RYGB was associated with a greater rate of morbidity. Conclusion: RYGB and SG seem to be associated with similar remission rates of metabolic syndrome at 4 years. RYGB yields greater weight loss with greater medium-term complications. Keywords: bariatric surgery, weight loss, diabetes, hypertension, hyperlipidemi