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An Optimized IES Method and Its Inhibitory Effects and Mechanisms on Food Intake and Body Weight in Diet-Induced Obese Rats: IES for Obesity

Abstract

Purpose

This paper aims to optimize stimulation parameters and durations for intestinal electrical stimulation (IES) and to explore the effects and mechanisms of chronic IES with optimized methodology in obesity rats.

Materials and Methods

Sixteen diet-induced obese (DIO) rats were tested for food intake with four different sets of IES parameters each lasting 1 week. Then, another 12 DIO rats were used to test the effect of IES on food intake with different stimulation durations. Finally, 16 DIO rats were treated with IES or sham-IES for 4 weeks. Meal patterns, food intake, and body weight were observed. Mechanisms involving gastrointestinal motility, ghrelin, and glucagon-like peptide-1 (GLP-1) were studied.

Results

(1) Acute IES with different parameters showed different inhibitory effects on food intake, and the most effective parameters were 0.6 s on, 0.9 s off, 80 Hz, 2 ms, and 4 mA with which 26.3% decrease in food intake was noted (p < 0.001). (2) IES with daily treatment of 12 h was most effective in suppressing food intake compared with 1 or 6 h. (3) Four-week IES reduced net weight by 10.9% (p < 0.05 vs. sham-IES) and epididymal fat pad weight by 13.9% (p < 0.001). (4) IES delayed gastric emptying (p < 0.001) and accelerated intestinal transit (p < 0.05). (5) IES increased both fasting and postprandial plasma levels of GLP-1 but not ghrelin.

Conclusion

Twelve-hour daily IES using optimized stimulation parameters reduces food intake and body weight in DIO rats by altering gastrointestinal motility and GLP-1. The IES methodology derived in this study may have a therapeutic potential for obesity.

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References

  1. Moore S, Hall JN, Harper S, et al. Global and national socioeconomic disparities in obesity, over-weight, and underweight status. J Obes. 2010;2010(ID 514674):11.

    Google Scholar 

  2. Meek CL, Lewis HB, Reimann F, et al. The effect of bariatric surgery on gastrointestinal and pancreatic peptide hormones. Peptides. 2016;77:28–37.

    CAS  Article  PubMed  Google Scholar 

  3. Bray GA, Frühbeck G, Ryan DH, et al. Management of obesity. Lancet. 2016;387(10031):1947–56.

    Article  PubMed  Google Scholar 

  4. Mans E, Serra-Prat M, Palomera E, et al. Sleeve gastrectomy effects on hunger, satiation, and gastrointestinal hormone and motility responses after a liquid meal test. Am J Clin Nutr. 2015;102(3):540–7.

    CAS  Article  PubMed  Google Scholar 

  5. Madsbad S, Dirksen C, Holst JJ. Mechanisms of changes in glucose metabolism and bodyweight after bariatric surgery. Lancet Diabetes Endocrinol. 2014;2(2):152–64.

    CAS  Article  PubMed  Google Scholar 

  6. Elder KA, Wolfe BM. Bariatric surgery: a review of procedures and outcomes. Gastroenterology. 2007;132(6):2253–71.

    Article  PubMed  Google Scholar 

  7. Weinstein AL, Marascalchi BJ, Spiegel MA, et al. Patient preferences and bariatric surgery procedure selection; the need for shared decision-making. Obes Surg. 2014;24(11):1933–9.

    Article  PubMed  Google Scholar 

  8. Franco J, Ruiz P, Palermo M, et al. A review of studies comparing three laparoscopic procedures in bariatric surgery: sleeve gastrectomy, Roux-en-Y gastric bypass and adjustable gastric banding. Obes Surg. 2011;21(9):1458–68.

    Article  PubMed  Google Scholar 

  9. Chen JDZ, Lin HC. Intestinal pacing accelerates small bowel transit slowed by fat-induced ileal brake. Dig Dis Sci. 2003;48:251–6.

    CAS  Article  PubMed  Google Scholar 

  10. Sun Y, Chen JD. Intestinal electric stimulation accelerates whole gut transit and promotes fat excrement in conscious rats. Int J Obes. 2009;33(8):817–23.

    CAS  Article  Google Scholar 

  11. Sun Y, Chen JDZ. Intestinal electrical stimulation decreases fat absorption in rats: therapeutic potential for obesity. Obes Res. 2004;12:1235–42.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. Yin J, Zhang J, Chen JD. Inhibitory effects of intestinal electrical stimulation on food intake, weight loss and gastric emptying in rats. Am J Physiol Regul Integr Comp Physiol. 2007;293(1):R78–82.

    CAS  Article  PubMed  Google Scholar 

  13. Zhang J, Zhu H, Chen JD. Central neuronal mechanisms of intestinal electrical stimulation: effects on duodenum distention-responsive (DD-R) neurons in the VMH of rats. Neurosci Lett. 2009;457(1):27–31.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. Khawaled R, Blumen G, Fabricant G, et al. Intestinal electrical stimulation decreases postprandial blood glucose levels in rats. Surg Obes Relat Dis. 2009;5(6):692–7.

    Article  PubMed  Google Scholar 

  15. Kelly KA, Code CF. Duodenal-gastric reflux and slowed gastric emptying by electrical pacing of the canine duodenal pacesetter potential. Gastroenterology. 1977;72(3):429–33.

    CAS  PubMed  Google Scholar 

  16. Soper NJ, Geisler KL, Sarr MG, et al. Regulation of canine jejunal transit. Am J Phys. 1990;259:G928–33.

    CAS  Google Scholar 

  17. Yin J, Ouyang H, Chen JD. Potential of intestinal electrical stimulation for obesity: a preliminary canine study. Obesity. 2007;15(5):1133–8.

    Article  PubMed  Google Scholar 

  18. Xu X, Lei Y, Chen JD. Duodenum electrical stimulation delays gastric emptying, reduces food intake and accelerates small bowel transit in pigs. 2011;19(2):442–8.

  19. Aberle J, Busch P, Veigel J, et al. Duodenal electric stimulation: results of a first-in-man study. Obes Surg. 2016;26(2):369–75.

  20. Xu X, Lei Y, Chen JD. Effects and mechanisms of electrical stimulation of the stomach, duodenum, ileum, and colon on gastric tone in dogs. Dig Dis Sci. 2010;55(4):895–901.

    Article  PubMed  Google Scholar 

  21. Akwari OE, Kelley KA, Steinbach JH, et al. Electric pacing of intact and transected canine small intestine and its computer model. Am J Phys. 1975;229:1188–97.

    CAS  Google Scholar 

  22. Bjorck S, Kelly KA, Phillips SF. Mechanisms of enhanced canine enteric absorption with intestinal pacing. Am J Phys. 1987;252:G548–53.

    CAS  Google Scholar 

  23. Cranley B, Kelly KA, Go VL, et al. Enhancing the anti-dumping effect of Roux gastrojejunostomy with intestinal pacing. Ann Surg. 1983;198(4):516–24.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. Ouyang X, Li S, Foreman R, et al. Hyperglycemia-induced small intestinal dysrhythmias attributed to sympathovagal imbalance in normal and diabetic rats. Neurogastroenterol Motil. 2015;27(3):406–15.

    CAS  Article  PubMed  Google Scholar 

  25. Lin X, Peters LJ, Hayes J, et al. Entrainment of segmental small intestinal slow waves with electrical stimulation in dogs. Dig Dis Sci. 2000;45(4):652–6.

    CAS  Article  PubMed  Google Scholar 

  26. Lin X, Hayes J, Peters LJ, et al. Entrainment of intestinal slow waves with electrical stimulation using intraluminal electrodes. Ann Biomed Eng. 2000;28(5):582–7.

    CAS  Article  PubMed  Google Scholar 

  27. Yin J. Chen JDz. Excitatory effects of synchronized intestinal electrical stimulation on small intestinal motility in dogs. Am J Physiol Gastrointest Liver Physiol. 2007;293(6):G1190–5.

    CAS  Article  PubMed  Google Scholar 

  28. Farley C, Cook JA, Spar BD, et al. Meal pattern analysis of diet-induced obesity in susceptible and resistant rats. Obes Res. 2003;11(7):845–51.

    Article  PubMed  Google Scholar 

  29. Li S, Maude-Griffin R, Pullan AJ, et al. Gastric emptying and Ca (2+) and K(+) channels of circular smooth muscle cells in diet-induced obese prone and resistant rats. Obesity (Silver Spring). 2013;21(2):326–35.

    CAS  Article  Google Scholar 

  30. Sallam HS, Oliveira HM, Gan HT, et al. Ghrelin improves burn-induced delayed gastrointestinal transit in rats. Am J Physiol Regul Integr Comp Physiol. 2007;292:R253–7.

    CAS  Article  PubMed  Google Scholar 

  31. Yin J, Hou X, Chen JD. Roles of interstitial cells of Cajal in intestinal transit and exogenous electrical pacing. Dig Dis Sci. 2006;51(10):1818–23.

    Article  PubMed  Google Scholar 

  32. Li S, Chen JD. Pulse width-dependent effects of intestinal electrical stimulation for obesity: role of gastrointestinal motility and hormones. Obes Surg. 2016 29.

  33. Shikora SA, Bergenstal R, Bessler M, et al. Implantable gastric stimulation for the treatment of clinically severe obesity: results of the SHAPE trial. Surg Obes Relat Dis. 2009;5(1):31–7.

    Article  PubMed  Google Scholar 

  34. Shikora SA, Storch K. Implantable gastric stimulation for the treatment of severe obesity: the American experience. Surg Obes Relat Dis. 2005;1(3):334–42.

    Article  PubMed  Google Scholar 

  35. Horbach T, Thalheimer A, Seyfried F, et al. Abiliti closed-loop gastric electrical stimulation system for treatment of obesity: clinical results with a 27-month follow-up. Obes Surg. 2015;25(10):1779–87.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. Miras M, Serrano M, Durán C, et al. Early experience with customized, meal-triggered gastric electrical stimulation in obese patients. Obes Surg. 2015;25(1):174–9.

    CAS  Article  PubMed  Google Scholar 

  37. Zhang J, Maude-Griffin R, Zhu H, et al. Gastric electrical stimulation parameter dependently alters ventral medial hypothalamic activity and feeding in obese rats. Am J Physiol Gastrointest Liver Physiol. 2011;301(5):G912–8.

    CAS  Article  PubMed  Google Scholar 

  38. Liu S, Hou XH, Chen JDZ. Therapeutic potential of duodenal electrical stimulation for obesity: acute effects on gastric emptying and water intake. Am J Gastroenterology. 2005;100:792–6.

    Article  Google Scholar 

  39. Liu J, Qiao X, Hou X, et al. Effect of intestinal pacing on small bowel transit and nutrient absorption in healthy volunteers. Obes Surg. 2009;19(2):196–201.

    Article  PubMed  Google Scholar 

  40. Liu J, Xiang Y, Qiao X, et al. Hypoglycemic effects of intraluminal intestinal electrical stimulation in healthy volunteers. Obes Surg. 2011;21(2):224–30.

    Article  PubMed  Google Scholar 

  41. Yin J, Chen JD. Mechanisms and potential applications of intestinal electrical stimulation. Dig Dis Sci. 2010;55(5):1208–20.

    Article  PubMed  Google Scholar 

  42. Fonken LK, Workman JL, Walton JC, et al. Light at night increases body mass by shifting the time of food intake. Proc Natl Acad Sci U S A. 2010;107(43):18664–9.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  43. Murphy KG, Bloom SR. Gut hormones and the regulation of energy homeostasis. Nature. 2006;444(7121):854–9.

    CAS  Article  PubMed  Google Scholar 

  44. Suzuki S, Ramos EJ, Goncalves CG, et al. Changes in GI hormones and their effect on gastric emptying and transit times after Roux-en-Y gastric bypass in rat model. Surgery. 2005;138(2):283–90.

    Article  PubMed  Google Scholar 

  45. Holdstock C, Zethelius B, Sundbom M, et al. Postprandial changes in gut regulatory peptides in gastric bypass patients. Int J Obes. 2008;32(11):1640–6.

    CAS  Article  Google Scholar 

  46. Laferrère B, Teixeira J, McGinty J, et al. Effect of weight loss by gastric bypass surgery versus hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes. J Clin Endocrinol Metab. 2008;93(7):2479–85.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Schwartz A, Ort T, Kajekar R, et al. Electrical stimulation of the isolated rat intestine in the presence of nutrient stimulus enhances glucagon-like peptide-1 release. Physiol Meas. 2010;31(9):1147–59.

    Article  PubMed  Google Scholar 

  48. Sandoval D, Dunki-Jacobs A, Sorrell J, et al. Impact of intestinal electrical stimulation on nutrient-induced GLP-1 secretion in vivo. Neurogastroenterol Motil. 2013;25(8):700–5.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by a VA MERIT grant (1I01BX002010-01A2).

Author information

Affiliations

Authors

Contributions

Xinyue Wan: Conduct the experiment and drafting of the manuscript.

Jieyun Yin: Data collection and analysis.

Robert Foreman: Data analysis and revising of the manuscript.

Jiande DZ Chen: Study design and critical revision of the manuscript.

Corresponding author

Correspondence to Jiande D. Z. Chen.

Ethics declarations

All ethical standards and requirements for animal studies have been rigidly followed.

Conflict of Interest

None of authors reported conflict of interest. Jiande Chen was supported by a VA Merit Grant.

Ethical Approval

This research was approved by the Animal Care and Use Committee of the Veterans Affairs Medical Center (Oklahoma City, OK).

Informed Consent

Does not apply.

Funding

This study was supported by a VA Merit grant (1I01BX002010).

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Cite this article

Wan, X., Yin, J., Foreman, R. et al. An Optimized IES Method and Its Inhibitory Effects and Mechanisms on Food Intake and Body Weight in Diet-Induced Obese Rats: IES for Obesity. OBES SURG 27, 3215–3222 (2017). https://doi.org/10.1007/s11695-017-2743-1

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  • DOI: https://doi.org/10.1007/s11695-017-2743-1

Keywords

  • Obesity
  • Gastrointestinal motility
  • Electric stimulation
  • Neuromodulation
  • Gut peptides