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Mechanism of Bile Acid Reabsorption in the Biliopancreatic Limb After Duodenal-Jejunal Bypass in Rats

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Abstract

Background

Bile acids (BAs) are important in the metabolic effects of bariatric surgery. Most BAs are reabsorbed in the ileum and recycled back to the liver. We have reported that this enterohepatic circulation was shortened by duodenal-jejunal bypass (DJB), and the biliopancreatic (BP)-limb plays an important role in reabsorption of BAs. However, the mechanism of BA reabsorption in BP-limb remains uncertain. We aimed to investigate the mechanisms of BA reabsorption after DJB, especially focusing on carrier-mediated transport of BAs and the impact of the presence or absence of lipids on BA reabsorption.

Methods

Otsuka-Long-Evans-Tokushima fatty rats or Sprague-Dawley rats were assigned to a control group and DJB group. BA levels in the divided small intestine were quantified with liquid chromatography-mass spectrometry. Labeled BA was injected and perfused with BA transporter inhibitors or mixture of lipids in the isolated BP-limb, and bile was sampled and analyzed.

Results

Conjugated BA levels in the BP-limb were significantly higher than that of the control group. BA absorption tended to decrease by the apical sodium-dependent BA transporter inhibitor and was significantly decreased by the organic anion-transporting peptide (OATP) inhibitor. BA absorption tended to increase in the absence of lipid solutions compared with that in the presence of lipid solutions.

Conclusion

We attributed the increased BA reabsorption in the BP-limb to lack of food in the BP-limb, which contains concentrated BAs and no lipids. OATP played an important role in BA reabsorption in the BP-limb. Therefore, BAs would be reabsorbed in different manners after DJB.

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References

  1. Rubino F, Nathan DM, Eckel RH, et al. Metabolic surgery in the treatment algorithm for type 2 diabetes: a joint statement by international diabetes organizations. Obes Surg. 2017;27:2–21.

    PubMed  Google Scholar 

  2. Buchwald H, Estok R, Fahrbach K, et al. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med. 2009;122:248–256.e5.

    PubMed  Google Scholar 

  3. Salminen P, Helmiö M, Ovaska J, et al. Effect of laparoscopic sleeve gastrectomy vs laparoscopic Roux-en-Y gastric bypass on weight loss at 5 years among patients with morbid obesity: the SLEEVEPASS randomized clinical trial. JAMA. 2018;319:241–54.

    PubMed  PubMed Central  Google Scholar 

  4. Lee WJ, Almulaifi AM, Tsou JJ, et al. Duodenal-jejunal bypass with sleeve gastrectomy versus the sleeve gastrectomy procedure alone: the role of duodenal exclusion. Surg Obes Relat Dis. 2015;11:765–70.

    PubMed  Google Scholar 

  5. Seki Y, Kasama K, Umezawa A, et al. Laparoscopic sleeve gastrectomy with duodenojejunal bypass for type 2 diabetes mellitus. Obes Surg. 2016;26:2035–44.

    PubMed  Google Scholar 

  6. Naitoh T, Kasama K, Seki Y, et al. Efficacy of sleeve gastrectomy with duodenal-Jejunal bypass for the treatment of obese severe diabetes patients in Japan: a retrospective multicenter study. Obes Surg. 2018;28:497–505.

    PubMed  Google Scholar 

  7. Imoto H, Shibata C, Ikezawa F, et al. Effects of duodeno-jejunal bypass on glucose metabolism in obese rats with type 2 diabetes. Surg Today. 2014;44:340–8.

    CAS  PubMed  Google Scholar 

  8. Miyachi T, Nagao M, Shibata C, et al. Biliopancreatic limb plays an important role in metabolic improvement after duodenal-jejunal bypass in a rat model of diabetes. Surgery. 2016;159:1360–71.

    PubMed  Google Scholar 

  9. Breen DM, Rasmussen BA, Kokorovic A, et al. Jejunal nutrient sensing is required for duodenal-jejunal bypass surgery to rapidly lower glucose concentrations in uncontrolled diabetes. Nat Med. 2012;18:950–5.

    CAS  PubMed  Google Scholar 

  10. Ryan KK, Tremaroli V, Clemmensen C, et al. FXR is a molecular target for the effects of vertical sleeve gastrectomy. Nature. 2014;509:183–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Ise I, Tanaka N, Imoto H, et al. Changes in enterohepatic circulation after duodenal-jejunal bypass and reabsorption of bile acids in the bilio-pancreatic limb. Obes Surg. 2019;29:1901–10.

    PubMed  Google Scholar 

  12. Dawson PA, Haywood J, Craddock AL, et al. Targeted deletion of the ileal bile acid transporter eliminates enterohepatic cycling of bile acids in mice. J Biol Chem. 2003;278:33920–7.

    CAS  PubMed  Google Scholar 

  13. Dawson PA, Hubbert M, Haywood J, et al. The heteromeric organic solute transporter alpha-beta, Ostalpha-Ostbeta, is an ileal basolateral bile acid transporter. J Biol Chem. 2005;280:6960–8.

    CAS  PubMed  Google Scholar 

  14. Amelsberg A, Schteingart CD, Ton-Nu HT, et al. Carrier-mediated jejunal absorption of conjugated bile acids in the guinea pig. Gastroenterology. 1996;110:1098–106.

    CAS  PubMed  Google Scholar 

  15. Amelsberg A, Jochims C, Richter CP, et al. Evidence for an anion exchange mechanism for uptake of conjugated bile acid from the rat jejunum. Am J Phys. 1999;276:G737–42.

    CAS  Google Scholar 

  16. Walters HC, Craddock AL, Fusegawa H, et al. Expression, transport properties, and chromosomal location of organic anion transporter subtype 3. Am J Physiol Gastrointest Liver Physiol. 2000;279:G1188–200.

    CAS  PubMed  Google Scholar 

  17. Wilson FA, Dietschy JM. Characterization of bile acid absorption across the unstirred water layer and brush border of the rat jejunum. J Clin Invest. 1972;51:3015–25.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Kawano K, Hirashima T, Mori S, et al. Spontaneous long-term hyperglycemic rat with diabetic complications. Otsuka Long-Evans Tokushima fatty (OLETF) strain. Diabetes. 1992;41:1422–8.

    CAS  PubMed  Google Scholar 

  19. Kawano K, Hirashima T, Mori S, et al. OLETF (Otsuka Long-Evans Tokushima fatty) rat: a new NIDDM rat strain. Diabetes Res Clin Pract. 1994;24(Suppl):S317–20.

    PubMed  Google Scholar 

  20. Funakoshi A, Miyasaka K, Jimi A, et al. Little or no expression of the cholecystokinin-A receptor gene in the pancreas of diabetic rats (Otsuka Long-Evans Tokushima fatty = OLETF rats). Biochem Biophys Res Commun. 1994;199:482–8.

    CAS  PubMed  Google Scholar 

  21. Moran TH, Katz LF, Plata-Salaman CR, et al. Disordered food intake and obesity in rats lacking cholecystokinin A receptors. Am J Phys. 1998;274:R618–25.

    CAS  Google Scholar 

  22. Panchal SK, Brown L. Rodent models for metabolic syndrome research. J Biomed Biotechnol. 2011;2011:351982.

    PubMed  Google Scholar 

  23. Tsuchiya T, Naitoh T, Nagao M, et al. Increased bile acid signals after duodenal-jejunal bypass improve non-alcoholic steatohepatitis (NASH) in a rodent model of diet-induced NASH. Obes Surg. 2018;28:1643–52.

    PubMed  Google Scholar 

  24. Aldini R, Montagnani M, Roda A, et al. Intestinal absorption of bile acids in the rabbit: different transport rates in jejunum and ileum. Gastroenterology. 1996;110:459–68.

    CAS  PubMed  Google Scholar 

  25. Marcus SN, Schteingart CD, Marquez ML, et al. Active absorption of conjugated bile acids in vivo. Kinetic parameters and molecular specificity of the ileal transport system in the rat. Gastroenterology. 1991;100:212–21.

    CAS  PubMed  Google Scholar 

  26. Sugawara T, Kushiro M, Zhang H, et al. Lysophosphatidylcholine enhances carotenoid uptake from mixed micelles by Caco-2 human intestinal cells. J Nutr. 2001;131:2921–7.

    CAS  PubMed  Google Scholar 

  27. Morita SY, Kobayashi A, Takanezawa Y, et al. Bile salt-dependent efflux of cellular phospholipids mediated by ATP binding cassette protein B4. Hepatology. 2007;46:188–99.

    CAS  PubMed  Google Scholar 

  28. Ikeda Y, Morita SY, Terada T. Cholesterol attenuates cytoprotective effects of phosphatidylcholine against bile salts. Sci Rep. 2017;7:306.

    PubMed  PubMed Central  Google Scholar 

  29. Bhutta HY, Rajpal N, White W, et al. Effect of Roux-en-Y gastric bypass surgery on bile acid metabolism in normal and obese diabetic rats. PLoS One. 2015;10:e0122273.

    PubMed  PubMed Central  Google Scholar 

  30. Flynn CR, Albaugh VL, Cai S, et al. Bile diversion to the distal small intestine has comparable metabolic benefits to bariatric surgery. Nat Commun. 2015;6:7715.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Kohli R, Setchell KD, Kirby M, et al. A surgical model in male obese rats uncovers protective effects of bile acids post-bariatric surgery. Endocrinology. 2013;154:2341–51.

    CAS  PubMed  PubMed Central  Google Scholar 

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

    PubMed  Google Scholar 

  33. McClintock C, Shiau YF. Jejunum is more important than terminal ileum for taurocholate absorption in rats. Am J Phys. 1983;244:G507–14.

    CAS  Google Scholar 

  34. Lewis MC, Root C. In vivo transport kinetics and distribution of taurocholate by rat ileum and jejunum. Am J Phys. 1990;259:G233–8.

    CAS  Google Scholar 

  35. van de Steeg E, Wagenaar E, van der Kruijssen CM, et al. Organic anion transporting polypeptide 1a/1b-knockout mice provide insights into hepatic handling of bilirubin, bile acids, and drugs. J Clin Invest. 2010;120:2942–52.

    PubMed  PubMed Central  Google Scholar 

  36. van de Steeg E, van Esch A, Wagenaar E, et al. High impact of Oatp1a/1b transporters on in vivo disposition of the hydrophobic anticancer drug paclitaxel. Clin Cancer Res. 2011;17:294–301.

    PubMed  Google Scholar 

  37. Gong L, Aranibar N, Han YH, et al. Characterization of organic anion-transporting polypeptide (Oatp) 1a1 and 1a4 null mice reveals altered transport function and urinary metabolomic profiles. Toxicol Sci. 2011;122:587–97.

    CAS  PubMed  Google Scholar 

  38. Mika A, Kaska L, Proczko-Stepaniak M, et al. Evidence that the length of bile loop determines serum bile acid concentration and glycemic control after bariatric surgery. Obes Surg. 2018;28:3405–14.

    PubMed  Google Scholar 

  39. Risstad H, Kristinsson JA, Fagerland MW, et al. Bile acid profiles over 5 years after gastric bypass and duodenal switch: results from a randomized clinical trial. Surg Obes Relat Dis. 2017;13:1544–53.

    PubMed  Google Scholar 

  40. Boerboom A, Homan J, Aarts E, et al. A long biliopancreatic and short alimentary limb results in more weight loss in revisional RYGB surgery. Outcomes of the randomized controlled ELEGANCE REDO trial. Surg Obes Relat Dis. 2019;15:60–9.

    PubMed  Google Scholar 

  41. Nergaard BJ, Leifsson BG, Hedenbro J, et al. Gastric bypass with long alimentary limb or long pancreato-biliary limb—long-term results on weight loss, resolution of co-morbidities and metabolic parameters. Obes Surg. 2014;24:1595–602.

    PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The authors thank Ms. Emiko Shibuya for the technical assistance and the staff of the Institute for Animal Experimentation, Graduate School of Medicine, Tohoku University, for assistance with animal husbandry and care.

Funding

This study was supported by the grant-in-aid for scientific research from the Japan Society for the Promotion of Science (Grant Nos.: 17K10619, 17K10575) and Gonryo Medical Scholarship Promotion Association (Anzai Memorial Prize for Diabetes Research).

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Authors and Affiliations

  1. Department of Surgery, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan

    Tomotaka Ueno, Naoki Tanaka, Hirofumi Imoto, Atsushi Kohyama, Kazuhiro Watanabe, Fuyuhiko Motoi, Takashi Kamei, Michiaki Unno & Takeshi Naitoh

  2. Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1, Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan

    Masamitsu Maekawa

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  1. Tomotaka Ueno
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Correspondence to Naoki Tanaka.

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All procedures in this study were approved by ethics committee for animal research of our institute.

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Ueno, T., Tanaka, N., Imoto, H. et al. Mechanism of Bile Acid Reabsorption in the Biliopancreatic Limb After Duodenal-Jejunal Bypass in Rats. OBES SURG 30, 2528–2537 (2020). https://doi.org/10.1007/s11695-020-04506-3

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