A Rodent Model of Adjustable Gastric Band Surgery—Implications for the Understanding of Underlying Mechanisms

Article · May 2009with11 Reads
DOI: 10.1007/s11695-008-9751-0
Abstract
Background Bariatric surgery is currently the only anti-obesity therapy that can deliver weight loss of up to 20–30% of body weight. Laparoscopic adjustable gastric banding (LAGB) and Roux-en-y gastric bypass are the most commonly performed of these surgeries. The mechanisms by which LAGB initiates an increase in satiety remain completely unknown. The aim of this study is to establish a rodent model of adjustable gastric banding (AGB) that will enable investigation of these mechanisms. Methods Sprague–Dawley rats were implanted with adjustable gastric bands immediately below the gastro-esophageal junction around the glandular stomach. This band, as in humans, can be inflated via an exteriorized port resulting in an incremental impact on the stomach. Results Rats with an incremental inflation of the AGB showed a clear stepwise reduction in food intake and body weight. Normal food intake and body weight gain were restored with band deflation. Barium-assisted X-ray of the stomach showed the formation of a small gastric pouch proximal to the inflated band in a manner analogous to the human LAGB. Conclusions This is the first animal model of the AGB that allows incremental inflation for optimal tightening of the band in the conscious animal with corresponding effects on food intake and body weight. This model will allow measurement of acute and chronic neural and hormonal changes following activation of the band in the conscious animal and will provide the potential to inform and improve surgical approaches that are at the forefront of obesity treatments.
    • These receptors are widely distributed throughout the entire length of the GI tract (Timmermans and Adriaensen, 2008). In a validated rodent model of AGB surgery (Kampe et al., 2009Kampe et al., , 2012 ), we have recently demonstrated that blocking the vagal afferent C-fibres in the region of the GEJ where the band is placed with capsaicin abolishes the band's effect of lowering food intake and reducing weight that is otherwise seen with an activated band. The increase in Fos-positive expression within neurons seen following band activation in the nucleus of the solitary tract (NTS) and medial aspect of the parabrachial nucleus (PBN) was also blocked with local capsaicin vagal blocking.
    [Show abstract] [Hide abstract] ABSTRACT: The global epidemic of obesity and its related disease in combination with robust physiological defence of intentional weight loss generates a pressing need for effective weight loss therapies. Bariatric surgery, which works very effectively at delivering substantial sustained weight loss, has been an enigma with respect to mechanism of action. Naive concepts of restriction and malabsorption do not explain the efficacy of the most commonly used bariatric procedures. This century has seen increased interest in unravelling the mystery of the mechanisms underlying surgery associated weight loss with a focus on integrative gastrointestinal (GI) physiology, gut-brain signalling, and beyond weight loss effects on metabolism. GI interventions, some very minor, can alter GI wall stretch and pressure receptors; a range of GI hormones affecting hunger and satiety; bile acid metabolism and signalling; the characteristics of GI microbiome; portal vein nutrient sensing; and circulating concentrations of amino acids. Understanding the mechanisms involved should present targets for less invasive effective therapies. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Article · Jun 2015
    • AGB surgery was performed in anesthetized rats (isoflurane) as previously described by Kampe et al. (16) and depicted in Fig. 1. Briefly, rats received laparotomy followed by isolation of the stomach and removal of the forestomach (fundectomy) using an ETS-FLEX 35-mm staple gun (Ethicon Endo-Surgery, Somerville, NJ).
    [Show abstract] [Hide abstract] ABSTRACT: Bariatric procedures vary in efficacy, but overall are more effective than behavioral and pharmaceutical treatment. Roux-en-Y Gastric Bypass causes increased secretion of Glucagon-like peptide 1 (GLP-1), and reduces body weight more than adjustable gastric banding (AGB), which does not trigger increased GLP-1 secretion. Since GLP-1-based drugs consistently reduce body weight, we hypothesized that GLP-1 receptor (GLP-1R) agonists would augment the effects of AGB. Male Long Evans rats with diet-induced obesity received AGB implantation or sham surgery. GLP-1R agonism, cannabinoid receptor-1 (CB1-R) antagonism, or vehicle was combined with inflation to evaluate interaction between AGB and pharmacological treatments. GLP1-R agonism reduced BW in both sham and AGB rats (left un-inflated) compared to vehicle-treated animals. Subsequent band inflation was ineffective in vehicle-treated rats, but enhanced weight loss stimulated by GLP1-R agonism. In contrast, there were no additional BW loss when CB1-R antagonism was given with AGB. We found band inflation to trigger neural activation in areas of the nucleus of the solitary tract known to be targeted by GLP1-R agonism, offering potential mechanism for the interaction. These data show that GLP-1R agonism, but not CB1-R antagonism, improves weight loss achieved by AGB, and suggest an opportunity to optimize bariatric surgery with adjunctive pharmacotherapy.
    Full-text · Article · Jun 2013
  • [Show abstract] [Hide abstract] ABSTRACT: Laparoscopic adjustable gastric bands (LAGB) are a safe and effective treatment for obesity. Conflicting data exist concerning their effect on the esophagus, gastroesophageal junction, and mechanism of action. These patients will increasingly require accurate assessment of their esophageal function. Twenty LAGB patients underwent high-resolution video manometry with the LAGB empty, 20% under, 20% over, and at their optimal volume. Twenty obese controls were also studied. Effects on esophageal motility, the lower esophageal sphincter (LES), and the gastroesophageal junction were measured. Transit during liquid and semisolid swallows was assessed. The intraluminal pressure at the level of LAGB was a mean of 26.9 (19.8) mm Hg. This pressure varied depending on the volume within the LAGB and was separate to and distal to the lower esophageal sphincter LES. The LES was attenuated compared to controls (10 vs 18 mm Hg; p < 0.01) although relaxed normally. Esophageal motility was well preserved at optimal volume compared to 20% overfilled, with 77% normal swallows vs 51%, p = 0.008. Repetitive esophageal contractions were observed in 40% of swallows at optimal volume compared to 16% in controls, p = 0.024. In comparison to controls, the transit of liquid, 21 vs 8 s (p < 0.001), and semisolids, 50 vs 16 s (p < 0.001), was delayed. In LAGB patients, the LES is attenuated, although relaxes normally. Esophageal motility is preserved, although disrupted by overfilling the band. In the optimally adjusted LAGB, a delay in transit of liquids and semisolids through the esophagus and band is produced, along with an increase in repeated esophageal contractions.
    Full-text · Article · May 2009
  • [Show abstract] [Hide abstract] ABSTRACT: Bariatric surgery is considered the most effective current treatment for morbid obesity. Since the first publication of an article by Kremen, Linner, and Nelson, many experiments have been performed using animal models. The initial experiments used only malabsorptive procedures like intestinal bypass which have largely been abandoned now. These experimental models have been used to assess feasibility and safety as well as to refine techniques particular to each procedure. We will discuss the surgical techniques and the postsurgical physiology of the four major current bariatric procedures (namely, Roux-en-Y gastric bypass, gastric banding, sleeve gastrectomy, and biliopancreatic diversion). We have also reviewed the anatomy and physiology of animal models. We have reviewed the literature and presented it such that it would be a reference to an investigator interested in animal experiments in bariatric surgery. Experimental animal models are further divided into two categories: large mammals that include dogs, cats, rabbits, and pig and small mammals that include rats and mice.
    Article · Apr 2010
  • [Show abstract] [Hide abstract] ABSTRACT: Metabolic surgery was developed through the application and experience gained from bariatric or weight loss procedures. Much of our knowledge from the procedures comes from the study of animal models, where they have revealed anatomic feasibility, systemic physiological elements and cellular metabolic effects. The first generation of operation included the jejunoileal bypass and partial ileal bypass that led to the development of the current procedures including Roux-en-Y gastric bypass, biliopancreatic diversion, adjustable gastric banding and sleeve gastrectomy. These operations carry significant metabolic benefits and can reduce the risk of diabetes, heart disease and cancer. Further insights from these animal models can reveal genetic, molecular and systemic effects that can enhance and develop the next generation of metabolic operations.
    Article · Dec 2010
  • [Show abstract] [Hide abstract] ABSTRACT: To assess the effects of different bariatric surgical procedures on the treatment of obesity and insulin resistance in high fat diet-induced obese (DIO) mice. Bariatric surgery is currently considered the most effective treatment for morbid obesity and its comorbidities; however, a systematic study of their mechanisms is still lacking. We developed bariatric surgery models, including gastric banding, sleeve gastrectomy, Roux-en-Y gastric bypass (RYGB), modified RYGB (mRYGB) and biliopancreatic diversion (BPD), in DIO mice. Body weight, body fat and lean mass, liver steatosis, glucose tolerance and pancreatic beta cell function were examined. All bariatric surgeries resulted in significant weight loss, reduced body fat and improved glucose tolerance in the short term (4 weeks), compared with mice with sham surgery. Of the bariatric surgery models, sleeve gastrectomy and mRYGB had higher success rates and lower mortalities and represent reliable restrictive and gastrointestinal (GI) bypass mouse bariatric surgery models, respectively. In the long term, the GI bypass procedure produced more profound weight loss, significant improvement of glucose tolerance and liver steatosis than the restrictive procedure. DIO mice had increased insulin promoter activity, suggesting overactivation of pancreatic beta cells, which was regulated by the mRYGB procedure. Compared with the restrictive procedure, the GI bypass procedure showed more severe symptoms of malnutrition following bariatric surgery. Both restrictive and GI bypass procedures provide positive effects on weight loss, fat composition, liver steatosis and glucose tolerance; however, in the long term, the GI bypass shows better results than restrictive procedures.
    Article · Jul 2011
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March 2012 · International journal of obesity (2005) · Impact Factor: 5.00
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