Development of murine bariatric surgery models: lessons learned

Abstract

Roux-en-Y gastric bypass (RYGB) improves comorbidities such as diabetes and hypertension and lowers the risk of obesity-related cancers. To better understand the physiologic and genetic influences of bariatric surgery, a reliable murine model is needed that can be extended to genetically engineered mice. Given the complexity of these procedures, few researchers have successfully implemented these techniques beyond larger rodent models. The purpose of our study was to develop a technically feasible and reproducible murine model for RYGB and sleeve gastrectomy (SG). Mice were converted to liquid diet perioperatively without fasting and housed in groups on raised wire platforms. SG involved significant reduction of stomach volume followed by multilayer repair of the gastrotomy. RYGB procedure consisted of side-to-side, functional end-to-side bowel anastomoses and exclusion of the stomach medial to the gastroesophageal junction. Sham surgeries consisted of enterotomies and gastrotomy followed by primary repair without resection or rerouting. Survival after incorporation of the aforementioned techniques was 100% in the SG group and 41% in the RYGB group at 1 mo after surgery. Only 26% of RYGB mortality was attributed to leak, obstruction, or stricture; the majority of postoperative mortality was due to stress, dumping, or malnutrition. Much of the survival challenge for this surgical model was related to perioperative husbandry, which is to be expected given their small stature and poor response to stress. Utilization of the perioperative and surgical techniques described will increase survival and feasibility of these technically challenging procedures, allowing for a better understanding of mechanisms to explain the beneficial effects of bariatric surgery.

Keywords: Bariatric surgery; Murine model; Roux-en-Y gastric bypass.

Figure 1

Roux-en-Y Gastric Bypass (RYGB) in the Mouse. (A) After a midline incision, the fascia was retracted to expose small intestine. (B) Identification of the ligament of Treitz. (C) Measurement of the biliary limb. (D) Transection of the small intestine. (E) Short segments of pediatric scalp vein IV tubing fed into both the proximal and distal small bowel lumens to stent the lumen open. (F) One segment of IV tubing was gently advanced distally in the small bowel to the location of the biliary and Roux limb anastomosis. (G) Anti-mesenteric enterotomies were made in the small bowel at the point of the future jejuno-jejunostomy. (H) After construction of the side-to-side, functional end-to-side jejuno-jejunostomy, the IV tubing was slid out of the blind opening in the biliary limb and the blind end of the biliary limb was suture ligated. (I) Completed RYGB anatomy. (J) Intra-abdominal fat pads placed between bowel and fascia. (K) Closure of the fascia. (L) Skin closure.

Figure 2

Roux-en-Y Gastric Bypass (RYGB). (A) Schematic of RYGB procedure. Both the jejuno-jejunostomy (J-J) and gastro-jejunostomy (G-J) are side-to-side, functional end-to-side anastomoses. Approximately 60% of the stomach volume is excluded by application of a vascular clip across the body of the stomach, just medial to the esophagus. (B) Completed RYGB.

Figure 3

Sleeve Gastrectomy. (A) Schematic of sleeve gastrectomy procedure. Approximately 80% of the stomach volume is removed and the gastrotomy is repaired in two layers. (B) Completed sleeve gastrectomy.

Figure 4

Weight Loss Following Bariatric Surgery. (A) Average weight loss following bariatric surgery. (B) Percentage of excess body weight lost following bariatric surgery. Abbreviations: (R) Roux-en-Y gastric bypass; (RS) Sham Roux-en-Y gastric bypass; (S) Sleeve gastrectomy; (SS) Sham sleeve gastrectomy; (*) denotes statistical significance of p≤0.01.