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Surgical models of Roux-en-Y gastric bypass surgery and sleeve gastrectomy in rats and mice

Abstract

Bariatric surgery is the only definitive solution currently available for the present obesity pandemic. These operations typically involve reconfiguration of gastrointestinal tract anatomy and impose profound metabolic and physiological benefits, such as substantially reducing body weight and ameliorating type II diabetes. Therefore, animal models of these surgeries offer unique and exciting opportunities to delineate the underlying mechanisms that contribute to the resolution of obesity and diabetes. Here we describe a standardized procedure for mouse and rat models of Roux-en-Y gastric bypass (80–90 min operative time) and sleeve gastrectomy (30–45 min operative time), which, to a high degree, resembles operations in humans. We also provide detailed protocols for both pre- and postoperative techniques that ensure a high success rate in the operations. These protocols provide the opportunity to mechanistically investigate the systemic effects of the surgical interventions, such as regulation of body weight, glucose homeostasis and gut microbiome.

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Figure 1: Schematic representations of clinical RYGB and SGx.
Figure 2: Procedural and animal care timeline.
Figure 3: RYGB in the rat.
Figure 4: Sleeve gastrectomy in the rat.
Figure 5: Representative body weight and food intake results26,32.

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References

  1. Ng, M. et al. 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. Lancet 384, 766–781 (2014).

    Article  Google Scholar 

  2. Flegal, K.M., Carroll, M.D., Ogden, C.L. & Curtin, L.R. Prevalence and trends in obesity among US adults, 1999–2008. JAMA 303, 235–241 (2010).

    Article  CAS  Google Scholar 

  3. Lenz, M., Richter, T. & Muhlhauser, I. The morbidity and mortality associated with overweight and obesity in adulthood: a systematic review. Dtsch. Arztebl. Int. 106, 641–648 (2009).

    PubMed  PubMed Central  Google Scholar 

  4. Centers for Disease Control and Prevention. National Diabetes Statistics Report: Estimates of Diabetes and Its Burden in the United States, 2014 (US Department of Health and Human Services, 2014).

  5. Ogden, C.L., Carroll, M.D., Kit, B.K. & Flegal, K.M. Prevalence of childhood and adult obesity in the United States, 2011–2012. JAMA 311, 806–814 (2014).

    Article  CAS  Google Scholar 

  6. Buchwald, H. et al. Bariatric surgery: a systematic review and meta-analysis. JAMA 292, 1724–1737 (2004).

    Article  CAS  Google Scholar 

  7. Sjostrom, L. et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N. Engl. J. Med. 351, 2683–2693 (2004).

    Article  Google Scholar 

  8. Stefater, M.A., Wilson-Perez, H.E., Chambers, A.P., Sandoval, D.A. & Seeley, R.J. All bariatric surgeries are not created equal: insights from mechanistic comparisons. Endocr. Rev. 33, 595–622 (2012).

    Article  CAS  Google Scholar 

  9. Mingrone, G. et al. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N. Engl. J. Med. 366, 1577–1585 (2012).

    Article  CAS  Google Scholar 

  10. Pories, W.J. et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann. Surg. 222, 339–350; discussion 350–352 (1995).

    Article  CAS  Google Scholar 

  11. Schauer, P.R. et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N. Engl. J. Med. 366, 1567–1576 (2012).

    Article  CAS  Google Scholar 

  12. Laferrere, B. Do we really know why diabetes remits after gastric bypass surgery? Endocrine 40, 162–167 (2011).

    Article  CAS  Google Scholar 

  13. Deitel, M. A brief history of the surgery for obesity to the present, with an overview of nutritional implications. J. Am. Coll. Nutr. 32, 136–142 (2013).

    Article  CAS  Google Scholar 

  14. Barnett, S.J. Surgical management of adolescent obesity. Adv. Pediatr. 60, 311–325 (2013).

    Article  Google Scholar 

  15. Bueter, M., Abegg, K., Seyfried, F., Lutz, T.A. & le Roux, C.W. Roux-en-Y gastric bypass operation in rats. J. Vis. Exp. 64, e3940 (2012).

    Google Scholar 

  16. Buchwald, H., Estok, R., Fahrbach, K., Banel, D. & Sledge, I. Trends in mortality in bariatric surgery: a systematic review and meta-analysis. Surgery 142, 621–632; discussion 632–635, (2007).

    Article  Google Scholar 

  17. John, S. & Hoegerl, C. Nutritional deficiencies after gastric bypass surgery. J. Am. Osteopath. Assoc. 109, 601–604 (2009).

    PubMed  Google Scholar 

  18. Chang, S.H. et al. The effectiveness and risks of bariatric surgery: an updated systematic review and meta-analysis, 2003–2012. JAMA Surg. 149, 275–287 (2014).

    Article  Google Scholar 

  19. Schauer, P.R. et al. Bariatric surgery versus intensive medical therapy for diabetes–3-year outcomes. N. Engl. J. Med. 370, 2002–2013 (2014).

    Article  Google Scholar 

  20. Carlin, A.M. et al. The comparative effectiveness of sleeve gastrectomy, gastric bypass, and adjustable gastric banding procedures for the treatment of morbid obesity. Ann. Surg. 257, 791–797 (2013).

    Article  Google Scholar 

  21. Stylopoulos, N., Hoppin, A.G. & Kaplan, L.M. Roux-en-Y gastric bypass enhances energy expenditure and extends lifespan in diet-induced obese rats. Obesity 17, 1839–1847 (2009).

    Article  Google Scholar 

  22. Zheng, H. et al. Meal patterns, satiety, and food choice in a rat model of Roux-en-Y gastric bypass surgery. Am. J. Physiol. Regul. Integr. Comp. Physiol. 297, R1273–1282 (2009).

    Article  CAS  Google Scholar 

  23. Bueter, M. et al. Gastric bypass increases energy expenditure in rats. Gastroenterology 138, 1845–1853 (2010).

    Article  Google Scholar 

  24. Meguid, M.M. et al. A surgical rat model of human Roux-en-Y gastric bypass. J. Gastrointest. Surg. 8, 621–630 (2004).

    Article  Google Scholar 

  25. Patrikakos, P. et al. A surgical rat model of sleeve gastrectomy with staple technique: long-term weight loss results. Obes. Surg. 19, 1586–1590 (2009).

    Article  Google Scholar 

  26. Saeidi, N. et al. Sleeve gastrectomy and Roux-en-Y gastric bypass exhibit differential effects on food preferences, nutrient absorption and energy expenditure in obese rats. Int. J. Obes. 36, 1396–1402 (2012).

    Article  CAS  Google Scholar 

  27. Schlager, A. et al. A mouse model for sleeve gastrectomy: applications for diabetes research. Microsurgery 31, 66–71 (2011).

    Article  Google Scholar 

  28. Ye, J. et al. GLP-1 receptor signaling is not required for reduced body weight after RYGB in rodents. Am. J. Physiol. Regul. Integr. Comp. Physiol. 306, R352–R362 (2014).

    Article  CAS  Google Scholar 

  29. Hao, Z., Zhao, Z., Berthoud, H.R. & Ye, J. Development and verification of a mouse model for Roux-en-Y gastric bypass surgery with a small gastric pouch. PloS ONE 8, e52922 (2013).

    Article  CAS  Google Scholar 

  30. Wilson-Perez, H.E. et al. The effect of vertical sleeve gastrectomy on food choice in rats. Int. J. Obes. 37, 288–295 (2013).

    Article  CAS  Google Scholar 

  31. Chambers, A.P. et al. Similar effects of roux-en-Y gastric bypass and vertical sleeve gastrectomy on glucose regulation in rats. Physiol. Behav. 105, 120–123 (2011).

    Article  CAS  Google Scholar 

  32. Saeidi, N. et al. Reprogramming of intestinal glucose metabolism and glycemic control in rats after gastric bypass. Science 341, 406–410 (2013).

    Article  CAS  Google Scholar 

  33. Kucharczyk, J., Nestoridi, E., Kvas, S., Andrews, R. & Stylopoulos, N. Probing the mechanisms of the metabolic effects of weight loss surgery in humans using a novel mouse model system. J. Surg. Res. 179, e91–e98 (2013).

    Article  Google Scholar 

  34. Hariri, N. & Thibault, L. High-fat diet-induced obesity in animal models. Nutr. Res. Rev. 23, 270–299 (2010).

    Article  CAS  Google Scholar 

  35. Chambers, A.P. et al. Weight-independent changes in blood glucose homeostasis after gastric bypass or vertical sleeve gastrectomy in rats. Gastroenterology 141, 950–958 (2011).

    Article  CAS  Google Scholar 

  36. Wickremesekera, K., Miller, G., Naotunne, T.D., Knowles, G. & Stubbs, R.S. Loss of insulin resistance after Roux-en-Y gastric bypass surgery: a time course study. Obes. Surg. 15, 474–481 (2005).

    Article  Google Scholar 

  37. Rizzello, M. et al. Early postoperative insulin-resistance changes after sleeve gastrectomy. Obes. Surg. 20, 50–55 (2010).

    Article  Google Scholar 

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Acknowledgements

This work was supported by US National Institutes of Health grant no. DK095558 to N.S.

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Authors

Contributions

N.S. developed and performed the operations; B.G.B. provided figures; N.S. and B.G.B. wrote the manuscript; K.U. contributed to the initial design of the experiments; and N.S. and M.L.Y. contributed to the conceptual development.

Corresponding authors

Correspondence to Martin L Yarmush or Nima Saeidi.

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The authors declare no competing financial interests.

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Bruinsma, B., Uygun, K., Yarmush, M. et al. Surgical models of Roux-en-Y gastric bypass surgery and sleeve gastrectomy in rats and mice. Nat Protoc 10, 495–507 (2015). https://doi.org/10.1038/nprot.2015.027

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