Name: techniques of sleeve gastrectomy and modified roux-en-y gastric bypass in mice
Uploaded: 2017-03-20T12:30:00
Description: Watch this Scientific Journal Video about Techniques of Sleeve Gastrectomy and Modified Roux-en-Y Gastric Bypass in Mice at JoVE.com

We thank Gilles Mithieux and Aude Barataud (INSERM U1213, Lyon, France) and Marie Liabeuf and Stephanie Lemarchand-Minde (Animal facility, l'Institut du Thorax, Nantes, France) for their help with the animal care protocol. This work was supported by grants from La r&#233;gion des Pays de la Loire, the Fondation d'Avenir, and the Casden Bank. We would like to thank Catherine Postic, Fadila Benhamed and Michelle Ca&#252;zac from l'institut Cochin for their hospitality and their help during the filming process.

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 de...

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	<li>Ng, M., Fleming, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Global,+regional,+and+national+prevalence+of+overweight+and+obesity+in+children+and+adults+during+1980-2013:+a+systematic+analysis+for+the+Global+Burden+of+Disease+Study+2013.">Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013.</a> The Lancet. 384 (9945), 766-781 (2014).</li><li>Calle, E. E., Thun, M. J., Petrelli, J. M., Rodriguez, C., Heath, C. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Body-mass+index+and+mortality+in+a+prospective+cohort+of+U.S.+adults.">Body-mass index and mortality in a prospective cohort of U.S. adults.</a> The New England Journal of Medicine. 341 (15), 1097-1105 (1999).</li><li>Sj&#246;str&#246;m, L., Lindroos, A. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lifestyle,+diabetes,+and+cardiovascular+risk+factors+10+years+after+bariatric+surgery.">Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery.</a> The New England Journal of Medicine. 351 (26), 2683-2693 (2004).</li><li>Buchwald, H., Avidor, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bariatric+surgery:+a+systematic+review+and+meta-analysis.">Bariatric surgery: a systematic review and meta-analysis.</a> JAMA. 292 (14), 1724-1737 (2004).</li><li>Yin, D. P., Gao, Q., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessment+of+different+bariatric+surgeries+in+the+treatment+of+obesity+and+insulin+resistance+in+mice.">Assessment of different bariatric surgeries in the treatment of obesity and insulin resistance in mice.</a> Annals of surgery. 254 (1), 73-82 (2011).</li><li>Buchwald, H., Oien, D. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Metabolic/Bariatric+Surgery+Worldwide+2008.">Metabolic/Bariatric Surgery Worldwide 2008.</a> Obesity Surgery. 19 (12), 1605-1611 (2009).</li><li>Liu, W., Zassoko, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Establishment+of+duodenojejunal+bypass+surgery+in+mice:+A+model+designed+for+diabetic+research.">Establishment of duodenojejunal bypass surgery in mice: A model designed for diabetic research.</a> Microsurgery. 28 (3), 197-202 (2008).</li><li>Lan, Z., Zassoko, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+of+techniques+for+gastrojejunal+bypass+surgery+in+obese+mice.">Development of techniques for gastrojejunal bypass surgery in obese mice.</a> Microsurgery. , (2010).</li><li>Schlager, A., Khalaileh, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+mouse+model+for+sleeve+gastrectomy:+Applications+for+diabetes+research.">A mouse model for sleeve gastrectomy: Applications for diabetes research.</a> Microsurgery. 31 (1), 66-71 (2011).</li><li>Troy, S., Soty, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intestinal+Gluconeogenesis+Is+a+Key+Factor+for+Early+Metabolic+Changes+after+Gastric+Bypass+but+Not+after+Gastric+Lap-Band+in+Mice.">Intestinal Gluconeogenesis Is a Key Factor for Early Metabolic Changes after Gastric Bypass but Not after Gastric Lap-Band in Mice.</a> Cell Metabolism. 8 (3), 201-211 (2008).</li><li>Seyfried, F., Lannoo, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Roux-en-Y+gastric+bypass+in+mice--surgical+technique+and+characterisation.">Roux-en-Y gastric bypass in mice--surgical technique and characterisation.</a> Obesity surgery. 22 (7), 1117-1125 (2012).</li></ol>

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...

The worldwide pandemic of obesity and diabetes is devastating in severity. Over two billion adults worldwide (30% of the population) are either overweight (BMI &#62;25 kg/m2) or obese (BMI &#62;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 loss3,4. A number of different surgical methods have been developed, but the sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are the two procedures most commonly used in clinical practice. During the SG procedure, 80% of the initial volume of the stomach is removed; thus, this technique is one of the restrictive surgeries that improves satiety. The RYGB is one of the restrictive-malabsorptive techniques. During RYGB, a small gastric pouch (1-2% of the total gastric volume) is created and the intestine is rearranged into a Y-shape, which delays digestion and the absorption of nutrients. These two techniques lead to significant body weight reductions and general improvements in frequently-associated comorbidities (e.g., hypertension, type 2 diabetes, and dyslipidemia)3, with a higher efficiency seen in RYGB. However, the molecular mechanisms behind the pleiotropic beneficial effects of the bariatric surgeries are often not fully elucidated. Due to the numerous genetically-modified strains available, a mouse model is the most convenient animal model to explore these molecular mechanisms.
However, bariatric procedures are difficult to directly adapt to small animal models and require high surgical dexterity. While SG can be easily performed in rodents with a very good survival rate, RYGB is lethal in mice due to severe bowel obstructions5. Different modified RYGB techniques have been proposed to counteract this problem, notably the oesojejunostomy5. Here, we present another alternative: the gastrojejunostomy without a stomach excision. This modified RYGB reproduces most of the beneficial effects observed in humans (i.e., a significant body weight reduction and an improvement in glucose and lipid homeostasis).
This manuscript aims to summarize and discuss the technical and experimental details of SG and RYGB in mice and to facilitate these procedures with the help of videos. A specific highlight will be made regarding the optimization of the preoperative and postoperative healthcare protocols that allow the reduction of vitamin and iron deficiencies.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Drugs</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>High Fat diet</td>
			<td>DIO diet</td>
			<td>Safe</td>
			<td></td>
		</tr>
		<tr>
			<td>Isoflurane</td>
			<td>Forane</td>
			<td>Baxter</td>
			<td></td>
		</tr>
		<tr>
			<td>Buprenorphin</td>
			<td>Buprecare</td>
			<td>Animalcare</td>
			<td></td>
		</tr>
		<tr>
			<td>Marbofloxacine</td>
			<td>Marbocyl</td>
			<td>Vetoquinol</td>
			<td></td>
		</tr>
		<tr>
			<td>Ammonium iron citrate, vitamins PP-B12</td>
			<td>Fercobsang</td>
			<td>Vetoquinol</td>
			<td></td>
		</tr>
		<tr>
			<td>Vitamins A-D3-E-K-B</td>
			<td>Vita Rongeur</td>
			<td>Virbac</td>
			<td></td>
		</tr>
		<tr>
			<td>NaCl 0,9%</td>
			<td>NaCl 0,9%</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Povidone solution</td>
			<td>Betadine Scrub</td>
			<td>Betadine</td>
			<td></td>
		</tr>
		<tr>
			<td>Povidone solution</td>
			<td>Betadine Solution</td>
			<td>Betadine</td>
			<td></td>
		</tr>
		<tr>
			<td>Carboptol 980 NF</td>
			<td>Ocrygel</td>
			<td>TVM</td>
			<td></td>
		</tr>
		<tr>
			<td>Name</td>
			<td>References</td>
			<td>Company</td>
			<td>Comments</td>
		</tr>
		<tr>
			<td>Sutures</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Prolene&#174;</td>
			<td>8.0, 6,5 mm</td>
			<td>Ethicon</td>
			<td></td>
		</tr>
		<tr>
			<td>Prolene&#174;</td>
			<td>5.0, 13 mm</td>
			<td>Ethicon</td>
			<td></td>
		</tr>
		<tr>
			<td>Name</td>
			<td>References</td>
			<td>Company</td>
			<td>Comments</td>
		</tr>
		<tr>
			<td>Surgical equipments</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Scissors</td>
			<td></td>
			<td>FST</td>
			<td></td>
		</tr>
		<tr>
			<td>Needle holder</td>
			<td>Olsen-Hegar</td>
			<td>FST</td>
			<td></td>
		</tr>
		<tr>
			<td>Micro scissors</td>
			<td>Vannas</td>
			<td>FST</td>
			<td></td>
		</tr>
		<tr>
			<td>Micro forceps&#160;</td>
			<td>Graefe</td>
			<td>FST</td>
			<td></td>
		</tr>
		<tr>
			<td>Micro forceps curved</td>
			<td>Graefe</td>
			<td>FST</td>
			<td></td>
		</tr>
		<tr>
			<td>Curved micro needle holder</td>
			<td>Castroviejo</td>
			<td>FST</td>
			<td></td>
		</tr>
		<tr>
			<td>Hemostatic collagen compress</td>
			<td>Pangen</td>
			<td>Urgo</td>
			<td></td>
		</tr>
		<tr>
			<td>Absorbent underpads</td>
			<td></td>
			<td>VWR</td>
			<td></td>
		</tr>
		<tr>
			<td>Name</td>
			<td>References</td>
			<td>Company</td>
			<td>Comments</td>
		</tr>
		<tr>
			<td>Specific equipments</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Hematology system&#160;</td>
			<td>Hemavet 950FS</td>
			<td>Hemavet</td>
			<td></td>
		</tr>
		<tr>
			<td>Glucose strips and glucometer</td>
			<td>One touch Verio</td>
			<td>Life scan</td>
			<td></td>
		</tr>
		<tr>
			<td>Stereo microscope</td>
			<td>MZ6</td>
			<td>Leica&#160;</td>
			<td></td>
		</tr>
	</tbody>
</table>

techniques of sleeve gastrectomy and modified roux-en-y gastric bypass in mice

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) &#62;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.

General conditions
The mean operative time for the SG procedure was 49.3 &#177; 1.5 min. We removed 62.8 &#177; 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 11th postoperative day because of a gastric obstruction caused by a bezoar.
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Watch this Scientific Journal Video about Techniques of Sleeve Gastrectomy and Modified Roux-en-Y Gastric Bypass in Mice at JoVE.com

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

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.

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 ...

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