Name: duodenal-jejunal bypass surgery in diet-induced obese diabetic mice
Uploaded: 2024-10-18T12:40:00.000+00:00
Duration: 8 min 50 s
Description: The prevalence of obesity and type 2 diabetes is a serious global health concern. Obesity is a major pathogenic factor in type 2 diabetes, cardiovascular ...

This study was supported by a grant from the Science and Technology Planning Project of Guangdong Province of China (No. 202002020069).

All protocol steps described below follow the guidelines of the Animal Care and Use Committee of the General Hospital of the Southern Theater Command under the approval number 2020112501.
1. General preoperative preparation
NOTE: Thirty 6-week-old male C57BL/6 mice were purchased. Mice were housed in a Specific Pathogen-Free (SPF) laboratory under a 12 h light/dark cycle; temperature, 22 &#177; 2 &#176;C; and humidity, 55-65%. Mice were given free access to water and fed a 60% kcal fat diet for 6 weeks to induce obesity. An intraperitoneal injection of 40 mg/kg streptozotocin was administered for 5 days to induce diabetes17. Among the thirty mice, twenty-two mice were screened for random blood glucose &#62; 300 mg/dL and randomly assigned to the DJB (n=15) and sham surgery (n=7) groups. Eight mice were excluded from the experiment due to substandard blood glucose.
<ol>
	<li>Fast the mice for 8 h prior to the surgery. Withdraw water 2 h before the surgery.</li>
	<li>Administer 1% sodium pentobarbital solution (6 mL/kg) and buprenorphine (1 mg/kg) intraperitoneally. Touch the toes or tails of the mice with forceps and ensure that the mice do not show any obvious twitching or shaking. Under adequate anesthesia, the mice can breathe freely without supplemental oxygen.</li>
	<li>Place the mice in the supine position on a sterileboardand under a stereomicroscope. Apply eye ointment to the eyes. Use an electric blanket to keep the mice warm throughout the procedure. Use sterile procedures, including surgical gowns, sterile gloves, and autoclaved instruments.</li>
	<li>In sham control mice, make the&#160;two incisions respectively in the duodenum 1 cm below the pylorus and in the jejunum 5 cm below the Treitz and then suture the incisions.</li>
</ol>
2. Duodenal jejunal bypass: Surgical Procedure
<ol>
	<li>Apply the depilatory paste from the xiphoid to the abdomen to remove hair from this region. Wipe off the cream and ensure that the skin is clean. Scrub the area three times with alternating scrub of iodine and alcohol solutions.</li>
	<li>Cover the mouse with a sterile drape, leaving the operational area exposed, and make a 2 cm incision from the xiphoid to the abdomen.</li>
	<li>Use an abdominal retractor to expose the abdominal cavity. Push away the abdominal fat using a wet cotton swab, and move the liver to the cephalic side to fully expose the stomach and bowels.</li>
	<li>The stomach and pylorus are below the liver, and the ligament of Treitz is at the distal duodenum. Double ligate the jejunum, 5 cm distal to the ligament of Treitz with a 6-0 silk suture (Figure 1A). Cut the jejunum at the midpoint of the two ligations and suture the jejunal stump with a 10-0 silk suture (Figure 1B). 
	NOTE: Avoid twisting the mesenteric blood vessels.</li>
	<li>Pull the proximal jejunal incision 5 cm along the bowel to the jejunum to create a jejunal-jejunal anastomosis. Align the two bowels horizontally, and then use a 10-0 silk suture to create the lateral anastomosis (Figure 1C). 
	NOTE: During surgery, keep the bowel moist with saline to reduce water loss. This will prevent the bowel from curling up and will make suturing easier.</li>
	<li>Secure both ends of the bowel and cut the incision to equal length (Figure 1D). Suture the second layer of the posterior intestinal wall with a full-thickness continuous suture. 
	NOTE: The incision length is approximately 0.5-0.6 cm, and the needle distance is ~0.5 mm.</li>
	<li>Secure both ends of the bowel and suture the anterior wall of the bowel. Suture the first layer of the anterior wall with a simple continuous suture and the second layer with a horizontal varus suture (Figure 1E-F). 
	NOTE: Swab the intestinal contents with cotton swabs to prevent infection of the abdominal cavity.</li>
	<li>Pull the distal jejunal incision into the duodenum 1 cm below the pylorus to create a duodenal-jejunal anastomosis (Figure 1G). Suture it using the same method as in steps 2.6-2.7&#160;(Figure 1H-K). 
	NOTE: Check the suture at the anastomotic corner to reduce anastomotic leakage.</li>
	<li>Ligate the bowel with the micro forceps and cut the bowel with the micro scissors. Double ligate the duodenum with a 6-0 silk suture, 2 mm from the distal end of the duodenal-jejunal anastomosis. Cut at the midpoint with micro scissors and suture the stump with a 10-0 silk suture (Figure 1L). 
	NOTE: The gastroduodenal vessels branch perpendicular to the head of the pancreas and are adjacent to the pylorus, requiring careful exploration of the vessels in the transverse section. The confluence of the common bile duct and duodenum was located, taking care not to damage the pancreas or the common bile duct.</li>
	<li>Rinse the abdominal cavity with 30 &#176;C saline. Return the bowel to the abdominal cavity. Suture the muscle and the skin separately with a 6-0 silk. Then, disinfect the skin with iodophor.</li>
	<li>After surgery, inject 30 &#176;C saline (30 mL/kg) subcutaneously in the back to prevent dehydration. Inject penicillin (10 mg/kg) intramuscularly to prevent infection.</li>
</ol>
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/66049/66049fig01.jpg" /> 
Figure 1: Duodenal-jejunal bypass procedure. (A)&#160;Location of the jejunum 5 cm distal to the ligament of Treitz. (B)&#160;Double ligate the jejunum with 6-0 silk, cut through the middle of the ligature. (C) Jejunal-jejunal anastomosis. (D)&#160;Make a 0.5-0.6 cm incision, and suture the posterior wall. (E-F)&#160;Complete Jejunal-jejunal anastomosis. (G) Pull the distal jejunal to the duodenum 1 cm below the pylorus. (H) Duodenal-jejunal anastomosis. (I)&#160;Cut the duodenal-jejunal anastomosis with a 0.5-0.6 cm incision and suture the posterior wall with a simple continuous suture. (J-K)&#160;Complete duodenal-jejunal anastomosis. (L)&#160;At 2 mm from the distal to the duodenal-jejunal anastomosis, double ligate the duodenum with 6-0 silk and cut through the middle of the ligature. <a href="https://www.jove.com/files/ftp_upload/66049/66049fig01large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
3. General postoperative care
<ol>
	<li>After surgery, place the mice on an electric blanket to prevent hypothermia. Allow the mice to crawl freely until fully awake before returning to their cages.</li>
	<li>On the postoperative day, restrict the food and water and inject 2 mL of saline subcutaneously into the back of the mice. On the first postoperative day, give 10 mL of 10% glucose and a functional drink (1:1 ratio) without food, and inject 1 mL of saline subcutaneously.</li>
	<li>On the second and third postoperative days, feed the mice with a mixture of 20 mL of 10% glucose and a functional drink. After the fourth day, give the mice pure water and a high-fat diet. Transitional feeding should be performed according to the postoperative recovery status in the following order: solution, semi-liquid, or solid food.</li>
	<li>Postoperative analgesia: inject buprenorphine (0.1 mg/kg) every 12 h from Days 1 to 3, and then once daily until Day 5.</li>
	<li>After surgery, observe the feeding conditions, activity, feces, and wound healing of the mice.</li>
</ol>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/66049/66049fig02.jpg" /> 
Figure 2: The&#160;diagram of DJB surgery. (A)&#160;Duodenal-jejunal anastomosis. (B)&#160;Jejunal-jejunal anastomosis. (C)&#160;Biliopancreatic limb. (D) Digestive limb. (E)&#160;Common limb. <a href="https://www.jove.com/files/ftp_upload/66049/66049fig02large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/66049/66049fig03.jpg" /> 
Figure 3:&#160;Anatomy of DJB surgery. (A)&#160;Duodenal-jejunal anastomosis. (B)&#160;Jejunal-jejunal anastomosis. (C)&#160;Biliopancreatic limb. (D) Digestive limb. (E)&#160;Common limb. <a href="https://www.jove.com/files/ftp_upload/66049/66049fig03large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
4. Postoperative evaluation of metabolic parameters
<ol>
	<li>Body weight measurement
	<ol>
		<li>Fast the mice for 8 h prior to the measurement. Weigh the mice weekly on Monday before and after surgery for 8 weeks.</li>
	</ol>
	</li>
	<li>Food intake measurement
	<ol>
		<li>House one mouse in each cage. Measure the amount of solid food in each cage before and after 24 h. The difference between the two values represents daily food intake.</li>
	</ol>
	</li>
	<li>Random blood glucose measurement
	<ol>
		<li>At 8:00 a.m. on the weekly Monday of measurement, collect a drop of blood from the tip of the mouse tail and apply it to a glucose strip inserted into the glucometer.</li>
	</ol>
	</li>
	<li>Oral glucose tolerance test
	<ol>
		<li>Eight weeks after the DJB surgery, fast the mice for 8 h before the oral glucose tolerance test. Collect a drop of blood from the tip of the mouse tail and place it on a glucose strip inserted into the glucometer. Administer an oral dose of 20% D-glucose (2 g/kg). Measure the blood glucose levels at 0, 15, 30, 60, 90, 120, 150, and 180 mins after gavage.</li>
	</ol>
	</li>
</ol>

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The authors declare no conflicts of interest.

In 1953, Varco et al.18 performed the first jejuno-ileal bypass as the beginning of bariatric surgery. Since then, numerous bariatric surgeries have been performed by surgeons. These surgeries have resulted in weight loss and improved metabolic complications4,19,20. Furthermore, in 1967, Mason and Ito21 performed the first Roux-en-Y gastric bypass (RYGB), which can effectively redu...

Obesity and type 2 diabetes are the most common chronic diseases in the world, and their prevalence is increasing among young individuals1. Bariatric surgery is the most effective treatment for obesity and diabetes, facilitating long-term blood glucose stabilitywhile also improving the complications associated with obesity2,3. There are several types of bariatric surgery, classified by whether they reduce gastric volume or intestinal absorption; these include restrictive, malabsorptive, and combination4,5.
Duodenal-jejunal bypass (DJB) was first developed by Rubino and Marescaux, who demonstrated that type 2 diabetes could be alleviated by connecting the duodenum and jejunum rather than by reducing the gastric volume6,7. DJB preserves the entire stomach and bypasses the entire duodenum and proximal jejunum. The bowel is divided into biliopancreatic, digestive, and common limbs6,8. DJB shares some similarities with bariatric surgeries, including Roux-en-Y gastric bypass (RYGB), mini-gastric bypass, biliopancreatic bypass, duodenal diversion, and DJB plus sleeve gastrectomy9. Compared to RYGB, DJB does not require a gastrointestinal anastomosis, which reduces the operative time and improves the success rate of the procedure. DJB is similar to RYGB in improving glucose metabolism but does not affect body weight10. After DJB surgery, rapid food delivery to the distal small intestine stimulates the secretion of glucagon-like peptide-1 (GLP-1), resulting in improved glucose metabolism11,12.
The use of animal models is essential for understanding the metabolic, cellular, and molecular pathways. Animal models of bariatric surgery have contributed to our understanding of potential mechanisms underlying obesity and diabetes13,14. However, due to the physiological differences between species, it is impossible to perfectly replicate human diseases in animal models15. Among various animal models available for research purposes, the diet-induced obesity (DIO) mouse model most closely resembles human obesity and metabolic syndrome16. Mice were selected for DJB surgery to determine the feasibility of the surgery and to provide techniques for further research. This manuscript provides a comprehensive summary of both technical aspects and experimental details of DJB surgery.

<table><tbody><tr><td>Abdominal retractor</td><td>F.S.T</td><td>17000-03</td><td>Colibri Retractor -3cm,retractor range 1.5cm/3cm long</td></tr><tr><td>1% sodium pentobarbital solution</td><td>Guangzhou Chemical Reagent Factory</td><td>/</td><td>&amp;nbsp;Dissolved 500mg of pentobarbital sodium powder in 50ml of normal saline to obtain 1% pentobarbital sodium solution.</td></tr><tr><td>Benzylpenicillin sodium for Injection</td><td>North China Pharmaceutical Company Ltd.</td><td>F2062121</td><td>Penicillin</td></tr><tr><td>Buprenorphine</td><td>Guangzhou Chemical Reagent Factory</td><td>/</td><td>Analgesia</td></tr><tr><td>Buprenorphine</td><td>Guangzhou Otsuka Pharmaceutical Co., Ltd</td><td>/</td><td>Analgesic</td></tr><tr><td>Citric acid-sodium citrate buffer</td><td>LEAGENE</td><td>R00522</td><td>Buffer solution</td></tr><tr><td>Cotton buds</td><td>HaoZheng Medical</td><td>60220610</td><td>Cotton swabs</td></tr><tr><td>Depilatory paste</td><td>Veet</td><td>AAPR-S222</td><td>Hair removal cream</td></tr><tr><td>Ear tag</td><td>ZEYA</td><td>SUS304</td><td>Ear-mark</td></tr><tr><td>Electric blanket</td><td>ZOSEN</td><td>ZS-CWDRT</td><td>Heat pad</td></tr><tr><td>Electronic scale</td><td>WETTLER TOLEDO</td><td>20060902-6</td><td>Measure the weight</td></tr><tr><td>Enteral nutritional powder</td><td>Abbott Laboratories</td><td>/</td><td>Nutrition powder</td></tr><tr><td>Eye ointment</td><td>Guangzhou Otsuka Pharmaceutical Co., Ltd</td><td>/</td><td>Protect the eyes</td></tr><tr><td>Glucometer</td><td>Roche</td><td>6993788001</td><td>Assess blood glucose</td></tr><tr><td>Graphpad Prism version 9.4.1</td><td>GraphPad Software</td><td>version 9.4.1</td><td>Software for statistical analysis</td></tr><tr><td>High-fat diet (High Fat [60FDC] Purified Rodent Diet)</td><td>Dyets</td><td>112252</td><td>60kcal% High Fat Diet</td></tr><tr><td>Micro Forceps</td><td>Jinzhong Medical</td><td>18-1140</td><td>Micro forceps</td></tr><tr><td>Micro needle holder</td><td>Jinzhong Medical</td><td>EMT-160-Z</td><td>Needle holder</td></tr><tr><td>Micro Scissors</td><td>Jinzhong Medical</td><td>YBC010</td><td>Micro scissors</td></tr><tr><td>Microscope camera</td><td>LAPSUN</td><td>E 2000</td><td>Video</td></tr><tr><td>Ophthalmic scissors</td><td>Jinzhong Medical</td><td>Y00030</td><td>Surgical scissors</td></tr><tr><td>Pentobarbital</td><td>Guangzhou Chemical Reagent Factory</td><td>/</td><td>Narcosis</td></tr><tr><td>Sodium chloride Injection</td><td>Guangzhou Otsuka Pharmaceutical Co., Ltd</td><td>B21L0301</td><td>NaCl 0.9%</td></tr><tr><td>Stereo microscope</td><td>ZEISS</td><td>Stemi 305</td><td>Binocular stereomicroscope</td></tr><tr><td>Streptozotocin</td><td>Sigma</td><td>S110910-1g</td><td>STZ</td></tr><tr><td>Suture line</td><td>LINGQIAO SUTURE</td><td>ZS-LQPMRZ5/0</td><td>Prolene 6/0,Prolene 10/0</td></tr><tr><td>Tissue forceps</td><td>Jinzhong Medical</td><td>H1701</td><td>Surgical forceps</td></tr></tbody></table>

duodenal-jejunal bypass surgery in diet-induced obese diabetic mice

The prevalence of obesity and type 2 diabetes is a serious global health concern. Obesity is a major pathogenic factor in type 2 diabetes, cardiovascular disease, and some cancers. Bariatric surgery offers a long-term and effective treatment option for both obesity and diabetes. Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are widely recognized as the most popular bariatric surgeries. Additionally, several exploratory bariatric surgeries have demonstrated promising therapeutic effects. Duodenal-jejunal bypass (DJB), specifically tailored for diabetics with low body mass index, has shown beneficial metabolic outcomes. However, its weight-independent metabolic benefits are not fully understood due to limited animal models. In this article, we describe the optimized care protocols and surgical techniques for performing DJB surgery in diet-induced obese (DIO) diabetic mice. Using a mouse model contributes to a better understanding of the nature of changes induced by DJB surgery while facilitating related clinical practice.

General conditions 
The mean operative time for the DJB procedure was 84.5 &#177; 2.6 min. Fifteen mice underwent DJB surgery, nine mice survived. As shown in Table 1, the majority of deaths occurred during surgery or in the following 7 days. The causes of postoperative death were bleeding (n=2) on postoperative day 1, anastomotic leakage (n=1) on postoperative day 4, anastomotic obstruction (n=2) on postoperative day 7, and unknown cause (n=1) three weeks after surgery.
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Duodenal-jejunal bypass (DJB) surgery can improve glucose metabolism and reduce insulin resistance. Here, we present a protocol to establish a stable and reliable mouse model of DJB.

Duodenal-Jejunal Bypass Surgery in Diet-Induced Obese Diabetic Mice

The prevalence of obesity and type 2 diabetes is a serious global health concern. Obesity is a major pathogenic factor in type 2 diabetes, cardiovascular ...

duodenal-jejunal-bypass-surgery-in-diet-induced-obese-diabetic-mice

Research

JoVE Journal

Medicine

450 Views.  Jinshazhou Hospital of Guangzhou University of Chinese Medicine. Duodenal-jejunal bypass (DJB) surgery can improve glucose metabolism and reduce insulin resistance. Here, we present a protocol to establish a stable and reliable mouse model of DJB.

Video: Duodenal-Jejunal Bypass Surgery in Diet-Induced Obese Diabetic Mice

Roux-en-Y Gastric Bypass Operation in Rats

Currently, the most effective therapy for the treatment of morbid obesity to induce significant and maintained body weight loss with a proven mortality benefit is bariatric surgery1,2. Consequently, there has been a steady rise in the number of bariatric operations done worldwide in recent years with the Roux-en-Y gastric bypass (gastric bypass) being the most commonly performed operation3. Against this background, it is important to understand the physiological mechanisms by which gastric bypass induces and maintains body weight loss. These mechanisms are yet not fully understood, but may include reduced hunger and increased satiation4,5, increased energy expenditure6,7, altered preference for food high in fat and sugar8,9, altered salt and water handling of the kidney10 as well as alterations in gut microbiota11. Such changes seen after gastric bypass may at least partly stem from how the surgery alters the hormonal milieu because gastric bypass increases the postprandial release of peptide-YY (PYY) and glucagon-like-peptide-1 (GLP-1), hormones that are released by the gut in the presence of nutrients and that reduce eating12.
During the last two decades numerous studies using rats have been carried out to further investigate physiological changes after gastric bypass. The gastric bypass rat model has proven to be a valuable experimental tool not least as it closely mimics the time profile and magnitude of human weight loss, but also allows researchers to control and manipulate critical anatomic and physiologic factors including the use of appropriate controls. Consequently, there is a wide array of rat gastric bypass models available in the literature reviewed elsewhere in more detail 13-15. The description of the exact surgical technique of these models varies widely and differs e.g. in terms of pouch size, limb lengths, and the preservation of the vagal nerve. If reported, mortality rates seem to range from 0 to 35%15. Furthermore, surgery has been carried out almost exclusively in male rats of different strains and ages. Pre- and postoperative diets also varied significantly.
Technical and experimental variations in published gastric bypass rat models complicate the comparison and identification of potential physiological mechanisms involved in gastric bypass. There is no clear evidence that any of these models is superior, but there is an emerging need for standardization of the procedure to achieve consistent and comparable data. This article therefore aims to summarize and discuss technical and experimental details of our previously validated and published gastric bypass rat model.

Numerous studies using gastric bypass rat models have been recently conducted to uncover the underlying physiological mechanisms of Roux-en-Y gastric bypass operations. This article aims to demonstrate and discuss the technical and experimental details of our published gastric bypass rat model to understand advantages and limitations of this experimental tool.

Currently, the most effective therapy for the treatment of morbid obesity to induce significant and maintained body weight loss with a proven mortality ...

Assessment of Gastric Emptying in Non-obese Diabetic Mice Using a [13C]-octanoic Acid Breath Test

Gastric emptying studies in mice have been limited by the inability to follow gastric emptying changes in the same animal since the most commonly used techniques require killing of the animals and postmortem recovery of the meal1,2. This approach prevents longitudinal studies to determine changes in gastric emptying with age and progression of disease. The commonly used [13C]-octanoic acid breath test for humans3 has been modified for use in mice4-6 and rats7 and we previously showed that this test is reliable and responsive to changes in gastric emptying in response to drugs and during diabetic disease progression8. In this video presentation the principle and practical implementation of this modified test is explained. As in the previous study, NOD LtJ mice are used, a model of type 1 diabetes9. A proportion of these mice develop the symptoms of gastroparesis, a complication of diabetes characterized by delayed gastric emptying without mechanical obstruction of the stomach10.
This paper demonstrates how to train the mice for testing, how to prepare the test meal and obtain 4 hr gastric emptying data and how to analyze the obtained data. The carbon isotope analyzer used in the present study is suitable for the automatic sampling of the air samples from up to 12 mice at the same time. This technique allows the longitudinal follow-up of gastric emptying from larger groups of mice with diabetes or other long-standing diseases.

Assessment of Gastric Emptying in Non-obese Diabetic Mice Using a [13C]-octanoic Acid Breath Test

Determination of gastric emptying with a non-invasive [13C]-octanoic acid breath test for tracking gastroparesis in female NOD LtJ mice.

Gastric emptying studies in mice have been limited by the inability to follow gastric emptying changes in the same animal since the most commonly used ...

Scaffold-supported Transplantation of Islets in the Epididymal Fat Pad of Diabetic Mice

Islet transplantation has been clinically proven to be effective at treating type 1 diabetes. However, the current intrahepatic transplantation strategy may incur acute whole blood reactions and result in poor islet engraftment. Here, we report a robust protocol for the transplantation of islets at the extrahepatic transplantation site-the epididymal fat pad (EFP)-in a diabetic mouse model. A protocol to isolate and purify islets at high yields from C57BL/6J mice is described, as well as a transplantation method performed by seeding islets onto a decellularized scaffold (DCS) and implanting them at the EFP site in syngeneic C57BL/6J mice rendered diabetic by streptozotocin. The DCS graft containing 500 islets reversed the hyperglycemic condition within 10 days, while the free islets without DCS required at least 30 days. The normoglycemia was maintained for up to 3 months until the graft was explanted. In conclusion, DCS enhanced the engraftment of islets into the extrahepatic site of the EFP, which could easily be retrieved and might provide a reproducible and useful platform for investigating the scaffold materials, as well as other transplantation parameters required for a successful islet engraftment.

This protocol demonstrates murine islet isolation and seeding onto a decellularized scaffold. Scaffold-supported islets were transplanted into the epididymal fat pad of streptozotocin (STZ)-induced diabetic mice. Islets survived at the transplantation site and reversed the hyperglycemic condition.

Islet transplantation has been clinically proven to be effective at treating type 1 diabetes. However, the current intrahepatic transplantation strategy ...

Bioengineering

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.

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 ...

One-anastomosis Gastric Bypass (OAGB) in Rats

The goal of this protocol is to set up a preclinical model of bariatric surgery and, more specifically, OAGB in obese rats. Based on this preclinical model, longitudinal studies can be carried out to provide an improved understanding of the mechanisms underlying the outcomes seen after bariatric surgery in humans. For this purpose, rats are operated on through a laparotomy under general anesthesia with isoflurane. First, the surgeon creates a long and tubular gastric pouch: after greater curve and hiatal dissection, the nonglandular stomach is stapled and removed. Then, the remaining stomach is also stapled in order to create a gastric tube and exclude the antrum of the stomach. After that, the surgeon performs a single end-to-side gastrojejunostomy 35 cm from the duodenojejunal angle. This limb length has been chosen in order to reproduce the same ratio between the biliopancreatic limb (BPL) and common limb (CL) length as in human bariatric surgery. The operation ends by aponeurotic and cutaneous closure. The early postoperative management consists of subcutaneous hydration, an intramuscular prophylactic antibiotic injection, a parietal injection of xylocaine, the administration of painkillers, and a progressive reintroduction of diet.

One-anastomosis Gastric Bypass OAGB in Rats

This protocol is for the performance of one-anastomosis gastric bypass (OAGB) on rat. The operator performs a long and tubular-stapled gastric pouch followed by hand-sewn anastomosis. For this model, the operator reproduces the same ratio between biliopancreatic and common limb in humans; therefore, the biliopancreatic limb measures 35 cm.

The goal of this protocol is to set up a preclinical model of bariatric surgery and, more specifically, OAGB in obese rats. Based on this preclinical ...

Sleeve Gastrectomy in Mice using Surgical Clips

The number of people who are overweight and obese is continually increasing both in the adult and adolescent populations. This coincides with the increased universal phenomenon of type 2 diabetes (T2D) and other metabolic problems. Bariatric surgery, such as SG, is currently one of the most effective and commonly used long-term treatment for obesity and T2D, but the association between them is not completely explored yet. The mechanisms underlying the outcomes seen after bariatric surgery in humans can be investigated based on preclinical animal studies. The SG reduces body weight, glucose levels and many metabolic parameters, and is easy to perform with a low incidence of complications. The goal of this work is to provide a simple method and an uncomplicated preclinical model of bariatric surgery in animals for researchers.

The prevalence of diabetes and obesity is continuously increasing worldwide. The mechanisms between diabetes, obesity and their associated mortality and co-morbidities need to be further investigated. Here, we present a protocol for sleeve gastrectomy (SG) in animals as an uncomplicated preclinical model of bariatric surgery.

The number of people who are overweight and obese is continually increasing both in the adult and adolescent populations. This coincides with the ...

A Protocol for Roux-en-Y Gastric Bypass in Rats using Linear Staplers

Roux-en-Y gastric bypass (RYGB) is commonly performed for the treatment of severe obesity and type 2 diabetes. However, the mechanism of weight loss and metabolic changes are not well understood. Multiple factors are thought to play a role, including reduced caloric intake, decreased nutrient absorption, increased satiety, the release of satiety-promoting hormones, shifts in bile acid metabolism, and alterations in the gut microbiota.
The rat RYGB model presents an ideal framework to study these mechanisms. Prior work on mouse models have had high mortality rates, ranging from 17 to 52%, limiting their adoption. Rat models demonstrate more physiologic reserve to surgical stimulus and are technically easier to adopt as they allow for the use of surgical staplers. One challenge with surgical staplers, however, is that they often leave a large gastric pouch which is not representative of RYGB in humans. 
In this protocol, we present a RYGB protocol in rats that result in a small gastric pouch using surgical staplers. Utilizing two stapler fires which remove the forestomach of the rat, we obtain a smaller gastric pouch similar to that following a typical human RYGB. Surgical stapling also results in better hemostasis than sharp division. Additionally, the forestomach of the rat does not contain any glands and its removal should not alter the physiology of RYGB.
Weight loss and metabolic changes in the RYGB cohort were significant compared to the sham cohort, with significantly lower glucose tolerance at 14 weeks. Furthermore, this protocol has an excellent survival of 88.9% after RYGB. The skills described in this protocol can be acquired without previous microsurgical experience. Once mastered, this procedure will provide a reproducible tool for studying the mechanisms and effects of RYGB.

Roux-en-Y gastric bypass (RYGB) is performed to treat obesity and diabetes. However, the mechanisms underlying RYGB's efficacy are not fully understood, and studies are limited by technical difficulty leading to high mortality in animal models. This article provides instructions on how to perform RYGB in rats with high success rates.

Roux-en-Y gastric bypass (RYGB) is commonly performed for the treatment of severe obesity and type 2 diabetes. However, the mechanism of weight loss and ...

Single-Anastomosis Duodeno-Ileal Bypass with Sleeve Gastrectomy Model in Mice

Obesity is a major health issue worldwide. As a response, bariatric surgeries have emerged to treat obesity and its related comorbidities (e.g., diabetes mellitus, dyslipidemia, non-alcoholic steatohepatitis, cardiovascular events, and cancers) through restrictive and malabsorptive mechanisms. Understanding the mechanisms by which these procedures allow such improvements often require their transposition into animals, especially in mice, because of the ease of generating genetically modified animals. Recently, the single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) has emerged as a procedure that uses both restrictive and malabsorptive effects, which is being used as an alternative to gastric bypass in case of major obesity. Thus far, this procedure has been associated with strong metabolic improvements, which has led to a marked increase in its use in daily clinical practice. However, the mechanisms underlying these metabolic effects have been poorly studied as a result of a lack of animal models. In this article, we present a reliable and reproducible model of SADI-S in mice, with a special focus on perioperative management. The description and use of this new rodent model will be helpful for the scientific community to better understand the molecular, metabolic, and structural changes induced by the SADI-S and to better define the surgical indications for clinical practice.

Single-anastomosis duodeno-ileal bypass (SADI-S) is an emerging bariatric procedure with important metabolic effects. In this article, we present a reliable and reproducible model of SADI-S in mice.

Obesity is a major health issue worldwide. As a response, bariatric surgeries have emerged to treat obesity and its related comorbidities (e.g., diabetes ...

A Murine Model of Vertical Sleeve Gastrectomy

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.

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.

Bariatric surgery, such as vertical sleeve gastrectomy (VSG), is a surgery of the gastrointestinal tract that is performed for the purpose of weight loss. ...

Biology

Roux-en-Y Gastric Bypass Procedure: A Bariatric Surgical Procedure for Gastric Resectioning in Murine Model

Source: Ayer, A., et al., <a href="https://www.jove.com/v/54905">Techniques of Sleeve Gastrectomy and Modified Roux-en-Y Gastric Bypass in Mice.</a> J. Vis. Exp. (2017).
This video describes a bariatric surgery-Roux-en-Y procedure. This involves the cutting of the jejunum- the middle portion of the intestine- to generate two intestinal limbs. The biliary limb is attached to the existing intestinal loop and the alimentary limb is attached to the stomach, creating a gastric bypass. The gastric bypass created here helps to decrease the nutrient uptake and efficiently reduces body weight.

Source: Ayer, A., et al., Techniques of Sleeve Gastrectomy and Modified Roux-en-Y Gastric Bypass in Mice. J. Vis. Exp. (2017).
This video describes a ...