Simulation of gastric bypass effects on glucose metabolism and non-alcoholic fatty liver disease with the Sleeveballoon device

Abstract

Background: Gastric bypass surgery is a very effective treatment of obesity and type 2 diabetes. However, very few eligible patients are offered surgery. Some patients also prefer less invasive approaches. We aimed to study the effects of the Sleeveballoona new device combining an intragastric balloon with a connecting sleeve, which covers the duodenal and proximal jejunal mucosaon insulin sensitivity, glycemic control, body weight and body fat distribution. Methods: We compared the effects of Sleeveballoon, Roux-en-Y Gastric-Bypass (RYGB) and sham-operation in 30 high-fat diet (HFD) fed Wistar rats. Whole body and hepatic insulin sensitivity and insulin signaling were studied. Transthoracic echocardiography was performed using a Vevo 2100 system (FUJIFILM VisualSonics Inc., Canada). Gastric emptying was measured using gastrografin. Findings: Hepatic (P = .023) and whole-body (P = .011) insulin sensitivity improved in the Sleeveballoon and RYGB groups compared with sham-operated rats. Body weight reduced in both Sleeveballoon and RYGB groups in comparison to the sham-operated group (503.1 ± 8.9 vs. 614.4 ± 20.6 g, P = .006 and 490.0 ± 17.7 vs. 614.4 ± 20.6 g, P = .006, respectively). Ectopic fat deposition was drastically reduced while glycogen content was increased in both liver and skeletal muscle. Gastric emptying (T 1/2) was longer (157.7 ± 29.2 min, P = .007) in the Sleeveballoon than in sham-operated rats (97.1 ± 26.3 min), but shorter in RYGB (3.5 ± 1.1 min, P b .0001). Cardiac function was better in Sleeveballoon and RYGB versus sham-operated rats. Interpretation: The Sleeveballoon reduces peripheral and hepatic insulin resistance, glycaemia, body weight and ectopic fat deposition to a similar level as RYGB, although the contribution of gastric emptying to blood glucose reduction is different.

New insight into the mechanisms of ectopic fat deposition improvement after bariatric surgery

“…Survival rates were 90% after sham operation, and 75% after SG. All experimental procedures were approved by the Catholic University of Rome Institutional Animal Care Committee and all methods were performed in accordance with the relevant guidelines and regulations 33 .…”

“…Ten milliliters of sterile 0.9% NaCl were administered subcutaneously before surgery. Access to the peritoneal cavity was obtained by 3-cm laparotomy 33 .…”

“…The lateral 80% of the stomach was excised leaving a tubular gastric remnant in continuity with the esophagus and with the pylorus and duodenum. After the operation, the abdominal wall was closed in layers 33 .…”

“…Protein content was determined using Bradford Protein Assay. Protein lysates (30 μg) were separated on 10% SDS-PAGE and transferred on PVDF membrane 33,39 . Membranes were probed overnight with Plin2, phospho-AktSer473, GSK3αβ Ser21/9, FoxO1 Thr24, AMPK Thr172, LAMP2A, and βActin.…”

“…Membranes with phospho-antibodies were stripped for 30 min at 56 °C and reprobed overnight with total Akt, GSK3α-β, AMPK and FoxO1respectively. Detection and analysis were performed respectively with Chemidoc XRS Image system and Image Lab 5.0 software (Bio-Rad Laboratories, Hercules, CA) 33,39 . Plin2 and LAMP2A were normalized with βActin while phospho-AktSer473, GSK3αβ Ser21/9, FoxO1 Thr24 and AMPK Thr172 were normalized with total Akt, GSK3α-β, FoxO1, AMPK respectively and expressed as a phospho-protein/total protein ratio.…”