Allan Sharp

Weight Loss and Metabolic Improvement in Morbidly Obese Subjects Implanted for 1 Year With an Endoscopic Duodenal-Jejunal Bypass Liner

Objective:To evaluate safety, weight loss, and cardiometabolic changes in obese subjects implanted with the duodenal-jejunal bypass liner (DJBL) for 1 year. Background:The DJBL is an endoscopic implant that mimics the duodenal-jejunal bypass component of the Roux-en-Y gastric bypass. Previous reports have shown significant weight loss and improvement in type 2 diabetes for up to 6 months. Methods:Morbidly obese subjects were enrolled in a single arm, open label, prospective trial and implanted with the DJBL. Primary endpoints included safety and weight change from baseline to week 52. Secondary endpoints included changes in waist circumference, blood pressure, lipids, glycemic control, and metabolic syndrome. Results:The DJBL was implanted endoscopically in 39 of 42 subjects (age: 36 ± 10 years; 80% female; weight: 109 ± 18 kg; BMI: 43.7 ± 5.9 kg/m2); 24 completed 52 weeks of follow-up. Three subjects could not be implanted due to short duodenal bulb. Implantation time was 24 ± 2 minutes. There were no procedure-related complications and there were 15 early endoscopic removals. In the 52-week completer population, total body weight change from baseline was −22.1 ± 2.1 kg (P < 0.0001) corresponding to 19.9 ± 1.8% of total body weight and 47.0 ± 4.4% excess of weight loss. There were also significant improvements in waist circumference, blood pressure, total and low-density lipoprotein cholesterol, triglycerides, and fasting glucose. Conclusions:The DJBL is safe when implanted for 1 year, and results in significant weight loss and improvements in cardiometabolic risk factors. These results suggest that this device may be suitable for the treatment of morbid obesity and its related comorbidities. This study was registered at www.clinicaltrials.gov (NCT00985491).

Splenic rupture as complication of sleeve gastrectomy

Splenic rupture as complication of sleeve gastrectomy Napoleón Salgado, M.D.*, Pablo Becerra, M.D., Eduardo Briceño, M.D., Allan Sharp, M.D., Alejandro Raddatz, M.D. Bariatric Surgery Program, Pontificia Universidad Católica de Chile Faculty of Medicine, Santiago, Chile Department of Digestive Surgery, Pontificia Universidad Católica de Chile Faculty of Medicine, Santiago, Chile Received July 19, 2011; accepted July 26, 2011 Surgery for Obesity and Related Diseases 8 (2012) e72–e74

589 Duodenojejunal Bypass Liner Increases Fasting and Postprandial Serum Levels of Bile Acids in Patients With Severe Obesity

information on anti-inflammatory or metabolic role of GPR120 at the level of intestinal epithelium is very limited. Further, GPR120 has been shown to be expressed in the intestine, however, its levels along the length of the intestine in various species have not been studied in detail. Aims: Our current studies, therefore, assessed the expression of GPR120 along the length of human, mouse and rat intestine. Further, we examined the anti-inflammatory effects and/or altered levels of the key aneroxigenic gut hormone glucagon-like peptide 1 (GLP1) in (i) model human intestinal epithelial Caco-2 and (ii) model mouse intestinal epithelial endocrine cell line STC-1 following GPR120 activation by synthetic (GW9508) or natural (ω-3 FA) agonists. Results: Both GPR120 mRNA and protein levels varied along the length of mouse and rat intestine in the order of proximal colon>cecum>distal colon>ileum>jejunum. Mucosal scrapings of different regions of organ donor human intestine also showed highest GPR120 protein level in the proximal colon. Cell-surface biotinylation and co-immunoprecipitation in Caco-2 cells, respectively, showed that GPR120 was internalized and bound to β-arrestin-2, a downstream signaling component of NF-κB activation, in response to 30 min exposure to GW9508 (50 μM) or eicosapentaenoic acid (EPA) (100 μM). These treatments also inhibited NF-κB reporter activity presumably via GPR120 binding to and sequestration of β-arrestin-2, inhibiting downstream signaling events. On the other hand, treatment of STC-1 cells with EPA or 10-trans,12-cis conjugated linoleic acid (100 μM, 6 hr) induced GLP1 intensity, as measured by immunofluorescence. However, in STC1 cells, GW9508/EPA treatments did not induce receptor internalization or sequestration of β-arrestin-2. Conclusion: Our studies for the first time demonstrate that agonist-stimulation of GPR120 in different cell types of the intestinal epithelium induces distinct signaling pathways to exert anti-inflammatory effects and modulate enteroendocrine function. Therefore, GPR120 appears to regulate diverse physiological processes at the level of intestinal epithelium to impact inflammatory and/or metabolic disorders. (Supported by NIH-NIDDK/ Bill & Melinda Gates Foundation).