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Ileal Transposition Decreases Plasma Lipopolysaccharide Levels in Association with Increased L Cell Secretion in Non-obese Non-diabetic Rats

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Abstract

Background

Chronic exposure to lipopolysaccharide (LPS) contributes to metabolic abnormalities, but there has been no study to evaluate plasma LPS levels after ileal transposition (IT). We examined the effect of IT on gut hormone secretion and plasma LPS levels and their correlation with metabolic parameters.

Methods

Sprague-Dawley rats underwent either IT or sham operation. After 4 weeks, oral glucose tolerance tests (OGTT) were performed and fasting plasma LPS and gut histology were analyzed.

Results

Compared with the sham group, food intake and body weight decreased, and insulin sensitivity increased in the IT group. During the OGTTs, glucagon, glucagon-like peptide-1 (GLP-1), GLP-2, and peptide YY (PYY) were significantly higher in the IT group than the sham group. The villi length, muscle thickness, and the density of GLP-1 and glucose-dependent insulinotropic polypeptide co-expressing cells (K/L-cells) increased in the transposed ileum compared with the ileum of the sham group. Fasting plasma LPS levels were lower in the IT group than the sham group (5.6 ± 0.2 vs. 6.8 ± 0.1 EU/ml, P = 0.002) and significantly correlated with insulin resistance (r = 0.755, P < 0.001). Plasma LPS levels were negatively correlated with PYY secretion (r = −0.710, P = 0.001), and GLP-2 secretion (r = −0.561, P = 0.019).

Conclusions

IT surgery decreased plasma LPS levels in a non-obese non-diabetic rat model, which was associated with improved insulin sensitivity and increased L-cell secretion.

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References

  1. Chen L, Magliano DJ, Zimmet PZ. The worldwide epidemiology of type 2 diabetes mellitus-present and future perspectives. Nat Rev Endocrinol. 2012;8(4):228–36.

    Article  CAS  Google Scholar 

  2. Sjostrom L, Lindroos AK, Peltonen M, et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med. 2004;351(26):2683–93.

    Article  PubMed  Google Scholar 

  3. Schauer PR, Kashyap SR, Wolski K, et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med. 2012;366(17):1567–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Mingrone G, Panunzi S, De Gaetano A, et al. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med. 2012;366(17):1577–85.

    Article  CAS  PubMed  Google Scholar 

  5. Dixon JB, le Roux CW, Rubino F, et al. Bariatric surgery for type 2 diabetes. Lancet. 2012;379(9833):2300–11.

    Article  PubMed  Google Scholar 

  6. Thaler JP, Cummings DE. Minireview: hormonal and metabolic mechanisms of diabetes remission after gastrointestinal surgery. Endocrinology. 2009;150(6):2518–25.

    Article  CAS  PubMed  Google Scholar 

  7. Cho YM. A gut feeling to cure diabetes: potential mechanisms of diabetes remission after bariatric surgery. Diab Metab J. 2014;38(6):406–15.

    Article  Google Scholar 

  8. Seeley RJ, Chambers AP, Sandoval DA. The role of gut adaptation in the potent effects of multiple bariatric surgeries on obesity and diabetes. Cell Metab. 2015;21(3):369–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Stefater MA, Wilson-Perez HE, Chambers AP, et al. All bariatric surgeries are not created equal: insights from mechanistic comparisons. Endocr Rev. 2012;33(4):595–622.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  Google Scholar 

  11. Rubino F, Forgione A, Cummings DE, et al. The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes. Ann Surg. 2006;244(5):741–9.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Cummings DE, Overduin J, Foster-Schubert KE. Gastric bypass for obesity: mechanisms of weight loss and diabetes resolution. J Clin Endocrinol Metab. 2004;89(6):2608–15.

    Article  CAS  PubMed  Google Scholar 

  13. Miras AD, le Roux CW. Mechanisms underlying weight loss after bariatric surgery. Nat Rev Gastroenterol Hepatol. 2013;10(10):575–84.

    Article  PubMed  Google Scholar 

  14. Strader AD, Vahl TP, Jandacek RJ, et al. Weight loss through ileal transposition is accompanied by increased ileal hormone secretion and synthesis in rats. Am J Physiol Endocrinol Metab. 2005;288(2):E447–53.

    Article  CAS  PubMed  Google Scholar 

  15. Strader AD, Clausen TR, Goodin SZ, et al. Ileal interposition improves glucose tolerance in low dose streptozotocin-treated diabetic and euglycemic rats. Obes Surg. 2009;19(1):96–104.

    Article  PubMed  Google Scholar 

  16. Wang TT, Hu SY, Gao HD, et al. Ileal transposition controls diabetes as well as modified duodenal jejunal bypass with better lipid lowering in a nonobese rat model of type II diabetes by increasing GLP-1. Ann Surg. 2008;247(6):968–75.

    Article  PubMed  Google Scholar 

  17. DePaula AL, Macedo AL, Schraibman V, et al. Hormonal evaluation following laparoscopic treatment of type 2 diabetes mellitus patients with BMI 20–34. Surg Endosc. 2009;23(8):1724–32.

    Article  PubMed  Google Scholar 

  18. Jimenez A, Casamitjana R, Flores L, et al. GLP-1 and the long-term outcome of type 2 diabetes mellitus after Roux-en-Y gastric bypass surgery in morbidly obese subjects. Ann Surg. 2013;257(5):894–9.

    Article  PubMed  Google Scholar 

  19. Jimenez A, Casamitjana R, Viaplana-Masclans J, et al. GLP-1 action and glucose tolerance in subjects with remission of type 2 diabetes after gastric bypass surgery. Diabetes Care. 2013;36(7):2062–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wilson-Perez HE, Chambers AP, Ryan KK, et al. Vertical sleeve gastrectomy is effective in two genetic mouse models of glucagon-like Peptide 1 receptor deficiency. Diabetes. 2013;62(7):2380–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Mokadem M, Zechner JF, Margolskee RF, et al. Effects of Roux-en-Y gastric bypass on energy and glucose homeostasis are preserved in two mouse models of functional glucagon-like peptide-1 deficiency. Mol Metab. 2014;3(2):191–201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ryan KK, Tremaroli V, Clemmensen C, Kovatcheva-Datchary P, Myronovych A, Karns R, et al. FXR is a molecular target for the effects of vertical sleeve gastrectomy. Nature 2014;509(7499):183 − +.

  23. Liou AP, Paziuk M, Luevano Jr JM, et al. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci Transl Med. 2013;5(178):178ra41.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Troseid M, Nestvold TK, Rudi K, et al. Plasma lipopolysaccharide is closely associated with glycemic control and abdominal obesity: evidence from bariatric surgery. Diabetes Care. 2013;36(11):3627–32.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Pussinen PJ, Havulinna AS, Lehto M, et al. Endotoxemia is associated with an increased risk of incident diabetes. Diabetes Care. 2011;34(2):392–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kallio KA, Hatonen KA, Lehto M, Salomaa V, Mannisto S, Pussinen PJ. Endotoxemia, nutrition, and cardiometabolic disorders. Acta Diabetol. 2014;52(2):395–404.

  27. Cani PD, Amar J, Iglesias MA, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56(7):1761–72.

    Article  CAS  PubMed  Google Scholar 

  28. Harte AL, Varma MC, Tripathi G, et al. High fat intake leads to acute postprandial exposure to circulating endotoxin in type 2 diabetic subjects. Diabetes Care. 2012;35(2):375–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–9.

    Article  CAS  PubMed  Google Scholar 

  30. Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999;22(9):1462–70.

    Article  CAS  PubMed  Google Scholar 

  31. Culnan DM, Albaugh V, Sun M, et al. Ileal interposition improves glucose tolerance and insulin sensitivity in the obese Zucker rat. Am J Physiol Gastrointest Liver Physiol. 2010;299(3):G751–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kohli R, Kirby M, Setchell KD, et al. Intestinal adaptation after ileal interposition surgery increases bile acid recycling and protects against obesity-related comorbidities. Am J Physiol Gastrointest Liver Physiol. 2010;299(3):G652–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Delzenne NM, Neyrinck AM, Backhed F, et al. Targeting gut microbiota in obesity: effects of prebiotics and probiotics. Nat Rev Endocrinol. 2011;7(11):639–46.

    Article  CAS  PubMed  Google Scholar 

  34. Meier JJ, Gethmann A, Gotze O, et al. Glucagon-like peptide 1 abolishes the postprandial rise in triglyceride concentrations and lowers levels of non-esterified fatty acids in humans. Diabetologia. 2006;49(3):452–8.

    Article  CAS  PubMed  Google Scholar 

  35. Hsieh J, Longuet C, Baker CL, et al. The glucagon-like peptide 1 receptor is essential for postprandial lipoprotein synthesis and secretion in hamsters and mice. Diabetologia. 2010;53(3):552–61.

    Article  CAS  PubMed  Google Scholar 

  36. Cani PD, Possemiers S, Van de Wiele T, et al. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut. 2009;58(8):1091–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Zhu W, Zhang W, Gong J, et al. Peptide YY induces intestinal proliferation in peptide YY knockout mice with total enteral nutrition after massive small bowel resection. J Pediatr Gastroenterol Nutr. 2009;48(5):517–25.

    Article  CAS  PubMed  Google Scholar 

  38. Cho YM, Kieffer TJ. K-cells and glucose-dependent insulinotropic polypeptide in health and disease. Vitam Horm. 2010;84:111–50.

    Article  CAS  PubMed  Google Scholar 

  39. Cho YM, Fujita Y, Kieffer TJ. Glucagon-like peptide-1: glucose homeostasis and beyond. Annu Rev Physiol. 2014;76:535–59.

    Article  CAS  PubMed  Google Scholar 

  40. Speck M, Cho YM, Asadi A, et al. Duodenal-jejunal bypass protects GK rats from {beta}-cell loss and aggravation of hyperglycemia and increases enteroendocrine cells coexpressing GIP and GLP-1. Am J Physiol Endocrinol Metab. 2011;300(5):E923–32.

    Article  CAS  PubMed  Google Scholar 

  41. Drozdowski LA, Clandinin MT, Thomson AB. Morphological, kinetic, membrane biochemical and genetic aspects of intestinal enteroplasticity. World J Gastroenterol. 2009;15(7):774–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Wewer Albrechtsen NJ, Hartmann B, Veedfald S, et al. Hyperglucagonaemia analysed by glucagon sandwich ELISA: nonspecific interference or truly elevated levels? Diabetologia. 2014;57(9):1919–26.

    Article  CAS  PubMed  Google Scholar 

  43. de Heer J, Pedersen J, Orskov C, et al. The alpha cell expresses glucagon-like peptide-2 receptors and glucagon-like peptide-2 stimulates glucagon secretion from the rat pancreas. Diabetologia. 2007;50(10):2135–42.

    Article  PubMed  Google Scholar 

  44. Campbell JE, Drucker DJ. Islet alpha cells and glucagon-critical regulators of energy homeostasis. Nat Rev Endocrinol. 2015;11(6):329–38.

    Article  CAS  PubMed  Google Scholar 

  45. Finan B, Yang B, Ottaway N, et al. A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents. Nat Med. 2015;21(1):27–36.

    Article  CAS  PubMed  Google Scholar 

  46. Pocai A, Carrington PE, Adams JR, et al. Glucagon-like peptide 1/glucagon receptor dual agonism reverses obesity in mice. Diabetes. 2009;58(10):2258–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Nausheen S, Shah IH, Pezeshki A, et al. Effects of sleeve gastrectomy and ileal transposition, alone and in combination, on food intake, body weight, gut hormones, and glucose metabolism in rats. Am J Physiol Endocrinol Metab. 2013;305(4):E507–18.

    Article  CAS  PubMed  Google Scholar 

  48. Ikezawa F, Shibata C, Kikuchi D, et al. Effects of ileal interposition on glucose metabolism in obese rats with diabetes. Surgery. 2012;151(6):822–30.

    Article  PubMed  Google Scholar 

  49. Kota SK, Ugale S, Gupta N, et al. Laparoscopic ileal interposition with diverted sleeve gastrectomy for treatment of type 2 diabetes. Diabetes Metabol Syndr. 2012;6(3):125–31.

    Article  Google Scholar 

  50. Cummings BP, Strader AD, Stanhope KL, et al. Ileal interposition surgery improves glucose and lipid metabolism and delays diabetes onset in the UCD-T2DM rat. Gastroenterology. 2010;138(7):46 e1–46.

    Article  Google Scholar 

  51. Cummings BP, Bettaieb A, Graham JL, et al. Bile-acid-mediated decrease in endoplasmic reticulum stress: a potential contributor to the metabolic benefits of ileal interposition surgery in UCD-T2DM rats. Dis Model Mech. 2013;6(2):443–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Conflict of Interest

The authors declare that there are no conflicts of interest. This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI14C1277).

Statement of Human and Animal Rights

This study has been approved by the Institutional Animal Care and Use Committee of Seoul National University (approval no. 13-0273).

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Correspondence to Young Min Cho.

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This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI14C1277).

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Oh, T.J., Lee, HJ. & Cho, Y.M. Ileal Transposition Decreases Plasma Lipopolysaccharide Levels in Association with Increased L Cell Secretion in Non-obese Non-diabetic Rats. OBES SURG 26, 1287–1295 (2016). https://doi.org/10.1007/s11695-015-1879-0

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  • DOI: https://doi.org/10.1007/s11695-015-1879-0

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