Techniques of Sleeve Gastrectomy and Modified Roux-en-Y Gastric Bypass in Mice

Summary

Bariatric surgery is the most efficient way to reduce body weight and the deadly metabolic complications (diabetes, obesity, and dyslipidemia) frequently associated with morbid obesity. Mouse models of bariatric surgery represent a unique asset for deciphering molecular mechanisms behind the beneficial effects of these surgeries on diabetes, hypertension, and dyslipidemia.

Abstract

Obesity is a major public health issue, with a prevalence of 4 to 28% for men and 6.2 to 36.5% for women in Europe (from 2003 to 2008). Morbid obesity is frequently associated with metabolic complications, such as type 2 diabetes, hypertension, and dyslipidemia, reducing life expectancy and quality. In the absence of any effective noninvasive treatments, bariatric surgery is a valuable therapeutic option for patients with morbid obesity (body mass index (BMI) >40 kg/m²), leading to long-term, sustained weight loss and improvements in metabolic complications. However, the underlying cellular and molecular mechanisms sustaining the beneficial effects of bariatric surgery are not yet fully understood. Due to the numerous genetically-modified strains available, the mouse model is the most convenient animal model to explore the molecular mechanisms behind the pleiotropic beneficial effects of bariatric surgeries. Here, we detailed the optimized healthcare methods and surgical protocols in mice for the two most widely-used bariatric surgeries: the sleeve gastrectomy and the modified Roux-en-Y gastric bypass. Deciphering the molecular mechanisms underlying the therapeutic effects of bariatric surgeries offers the promise of identifying new therapeutics targets.

Introduction

The worldwide pandemic of obesity and diabetes is devastating in severity. Over two billion adults worldwide (30% of the population) are either overweight (BMI >25 kg/m²) or obese (BMI >30 kg/m²)¹. This can come along with metabolic complications, such as type 2 diabetes, hypertension, and dyslipidemia, leading to increased morbidity and mortality. Obesity increases the overall mortality and the prevalence of cancer². Due to the lack of any effective noninvasive treatments, bariatric surgery represents the only option that can lead to long-term, sustained weight loss³....

Protocol

Animal and housing: Obtain 8-week-old C57Bl/6 male mice. At 10 weeks old, give the C57Bl/6 mice free access to water and a high-fat diet (DIO diet: 35% kcal from fat, 25.8% caseine, 1.30% mineral AIN, 1.30% vitamins, 1.70% dicalcium phosphate, 0.7% calcium carbonate, 2.10% citrate potassium, 0.026% choline bitartrate, 8.9% sucrose, 0.384% cystine, 6.5% cellulose, 31.7% lard, 3.3% soybean oil, and 16.29% maltodextrine) for 8 (SG) or 14 (RYGB) weeks prior to the bariatric surgeries. To promote weight gain, give the mice dedicated to the RYGB surgery (sham & RYGB) water containing 20% fructose (w/v) in addition to the high-fat diet.

Ethics....

Results

General conditions

The mean operative time for the SG procedure was 49.3 ± 1.5 min. We removed 62.8 ± 5.0 mg of stomach, which represents about 80% percent of the stomach. No mice died during the surgery or during the following seven days. One mouse (7.1%) died on the 11^th postoperative day because of a gastric obstruction caused by a bezoar.

Discussion

To overcome the growing epidemic of obesity, the first bariatric surgery procedures emerged in the 1960s in the United States. Since then, the number of procedures performed worldwide each year still increase, and today, these techniques represent the best therapeutic option for the management of morbid obesity⁶. Among the procedures developed, SG and RYGB are the two most popular methods used in clinical practice⁴. Animal models, notably rodents, have been used to decipher.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Drugs
High Fat diet	DIO diet	Safe
Isoflurane	Forane	Baxter
Buprenorphin	Buprecare	Animalcare
Marbofloxacine	Marbocyl	Vetoquinol
Ammonium iron citrate, vitamins PP-B12	Fercobsang	Vetoquinol
Vitamins A-D3-E-K-B	Vita Rongeur	Virbac
NaCl 0.9%	NaCl 0,9%
Povidone solution	Betadine Scrub	Betadine
Povidone solution	Betadine Solution	Betadine
Carboptol 980 NF	Ocrygel	TVM
Name	References	Company	Comments
Sutures
Prolene®	8.0, 6,5 mm	Ethicon
Prolene®	5.0, 13 mm	Ethicon
Name	References	Company	Comments
Surgical equipments
Scissors		FST
Needle holder	Olsen-Hegar	FST
Micro scissors	Vannas	FST
Micro forceps	Graefe	FST
Micro forceps curved	Graefe	FST
Curved micro needle holder	Castroviejo	FST
Hemostatic collagen compress	Pangen	Urgo
Absorbent underpads		VWR
Name	References	Company	Comments
Specific equipments
Hematology system	Hemavet 950FS	Hemavet
Glucose strips and glucometer	One touch Verio	Life scan
Stereo microscope	MZ6	Leica