A Murine Model of Vertical Sleeve Gastrectomy

Summary

The following describes the performance of vertical sleeve gastrectomy in mice. This is a type of weight-loss surgery that involves removal of approximately 70% of the stomach.

Abstract

Bariatric surgery, such as vertical sleeve gastrectomy (VSG), is a surgery of the gastrointestinal tract that is performed for the purpose of weight loss. Bariatric surgery is currently the most effective long-term treatment for obesity. In addition to weight loss, bariatric surgery produces additional health benefits such as remission of type 2 diabetes, remission of hypertension, and decreased risk of developing certain types of cancer. The mechanisms beyond weight loss for these benefits remain incompletely defined. Therefore, animal models of bariatric surgery are being developed and validated to identify the mechanisms leading to these benefits, with the goal of improving understanding of gastrointestinal physiology and identifying new therapeutic targets. VSG has become the most commonly performed bariatric procedure in the clinic in the United States because it is highly effective at producing weight loss and metabolic improvement, and is simpler to perform than other bariatric procedures. Therefore, we have developed and validated a murine model of VSG. This murine VSG model recapitulates many of the effects of VSG seen in humans, including improved glucose and blood pressure regulation. The method is based on isolation of the stomach, ligation of gastric vessels, and removal of 70% of the stomach by transecting along the greater curvature of the stomach. We have successfully applied this surgical protocol to various genetically modified mouse lines to define the mechanistic contributors to the benefits of VSG. Furthermore, this murine VSG model has been combined with other surgical techniques, to achieve deeper mechanistic insight. Therefore, this is a simple and versatile model for studying gastrointestinal physiology and the health benefits of bariatric surgery.

Introduction

As the obesity epidemic continues to grow worldwide bariatric surgery has gained popularity as it is the most effective long-term treatment for obesity¹. Unfortunately, weight loss by diet and exercise is difficult to achieve and relatively ineffective over the long-term^2,3. Bariatric surgery, such as vertical sleeve gastrectomy (VSG), is defined as the manipulation of the gastrointestinal tract for the purpose of weight loss^1,4. Although weight loss is a prominent outcome of bariatric surgery, bariatric surgery provides other h....

Protocol

All experimental protocols have been approved by the Cornell University Institutional Animal Care and Use Committee.

1. Pre-surgical Preparation

NOTE: Study mice are typically on a C57BL diet-induced obese background to make studies translationally relevant to human obesity and insulin resistance. Male and female mice may be studied as described in the subsequent steps.

1. At an age of 2 months, place mice on a 45% or 60% high fat diet for 2 months (see Table of Materials).
   NOTE: Mice are fed a high fat diet to create an obese and insulin resistant phenotype. Shorter or longer per....

Results

The sham and VSG procedures are depicted in Figure 1. Figure 1A shows where the suture line is placed along the gastric walls during the sham procedure. This same area is where the stomach is cut during VSG surgery. Figure 1B shows the tubular remnant of stomach left after performance of VSG.

Statistics and Data Analysis

Discussion

Bariatric surgery is the most effective long-term treatment for obesity and results in other health benefits such as high rates of type 2 diabetes and hypertension remission^1,9,15. Murine models of bariatric surgery provide a powerful tool with which to identify the mechanisms by which bariatric surgery causes rapid and pronounced improvements in obesity comorbidities. Furthermore, murine models of bariatric surgery provide a no.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
45% high fat diet	Research Diets	D12451
60% high fat diet	Research Diets	D12492
Boost	Nestle	160-67538	rich chocolate flavor
6-0 Suture	Ethicon	Z432	monofilament absorbable/taper
7-0 Suture	Covidien	8866127-01	monofilament absorbable/taper
Cotton Swabs	Fisherbrand	23-400-118	small
Cotton Swabs	Fisherbrand	233-400-101	large
Gauze	Various		4x4 4 ply and 2x2 4 ply
Foil	Various
Surgery drape	Various
0.9% saline solution	Various
LRS	Hospira	170RX
Betadine	Various
Alcohol	Various
Eye Ointment	Paralube® Vet Ointment	17033-211-38
Tissue Adhesive	Vetbond	1469SB
Meloxicam (Metacam)	Boehringer Ingelheim	141-213	5 mg/ml
Enrofloxacin	Baytril	08713254-186599	22.7 mg/ml
Thin tipped hemostats	Fine Science Tools	13021-12
Metzenbaum Scissor	Fine Science Tools	14018-18
Iris Scissors	Fine Science Tools	14058-09
Dumont Forcep	Fine Science Tools	11251-20
Serrated Forcep	Fine Science Tools	11020-12
Gavage needle	Fine Science Tools	18060-20
Microneedle driver	Fine Science Tools	12075-14
Spring Scissor	Fine Science Tools	15396-00
Insulin syringe	Various
1mL syringe	Various
20mL syringe	Various
Glucometer (one touch ultra mini)	Lifescan	70021208
Multiplex insulin and GLP-1 kit	Meso Scale Discovery	K15171C-1
GraphPad Prism 6.00	GraphPad Software
Nestlets	Ancare	NES3600