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Changes in Enterohepatic Circulation after Duodenal–Jejunal Bypass and Reabsorption of Bile Acids in the Bilio-Pancreatic Limb

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Abstract

Background and Aims

Duodenal–jejunal bypass (DJB) shows great effects on weight loss and diabetes improvement. Previously, we reported that the bilio-pancreatic (BP) limb plays an important role in glycemic improvement and in serum bile acid (BA) level increase as reported by Miyachi et al. (Surgery 159(5):1360–71, 2016). This study aimed to investigate the mechanism of BA elevation after DJB and the relationship between these effects and BP-limb length.

Methods

Otsuka Long-Evans Tokushima Fatty rats with diabetes were randomly assigned into four groups: one sham group and three DJB groups. Three DJB groups were defined according to the BP-limb length: 0 cm, 15 cm, and 30 cm. The lengths of the alimentary limb and common channel were set equally in each DJB groups. Body weight, glucose tolerance, and BA levels in the liver, bile juice, portal vein, and intestinal contents were assessed postoperatively. Changes in enterohepatic circulation of BAs were assessed using labeled BA.

Results

BA elevation after DJB was higher with longer BP-limb. In the 30-cm group, the serum total BA level and BA levels in the portal vein, liver, and bile juice were greater than those in other groups. The enterohepatic circulation was shortened in the 15-cm and 30-cm groups.

Conclusions

Shortening of the “enterohepatic circulation” by early reabsorption of BAs in the BP-limb, not by the early influx of bile juice into the ileum, was the main cause of BA elevation after DJB. Thus, glycemic improvement and elevation of BA concentration after DJB depend on the BP-limb length.

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References

  1. Buchwald H, Oien DM. Metabolic/bariatric surgery worldwide 2011. Obes Surg. 2013;23(4):427–36.

    Article  PubMed  Google Scholar 

  2. Sjostrom L, Narbro K, Sjostrom CD, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357(8):741–52.

    Article  PubMed  Google Scholar 

  3. Mingrone G, Panunzi S, De Gaetano A, et al. Bariatric-metabolic surgery versus conventional medical treatment in obese patients with type 2 diabetes: 5 year follow-up of an open-label, single-centre, randomised controlled trial. Lancet. 2015;386(9997):964–73.

    Article  PubMed  Google Scholar 

  4. 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(6):950–5.

    Article  CAS  PubMed  Google Scholar 

  5. 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(4):765–70.

    Article  PubMed  Google Scholar 

  6. Seki Y, Kasama K, Umezawa A, et al. Laparoscopic sleeve gastrectomy with duodenojejunal bypass for type 2 diabetes mellitus. Obes Surg. 2016;26(9):2035–44.

    Article  PubMed  Google Scholar 

  7. 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(2):497–505.

    Article  PubMed  Google Scholar 

  8. Ionut V, Bergman RN. Mechanisms responsible for excess weight loss after bariatric surgery. J Diabetes Sci Technol. 2011;5(5):1263–82.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Meryn S, Stein D, Straus EW. Pancreatic polypeptide, pancreatic glucagon and enteroglucagon in morbid obesity and following gastric bypass operation. Int J Obes. 1986;10(1):37–42.

    CAS  PubMed  Google Scholar 

  10. Batterham RL, Cummings DE. Mechanisms of diabetes improvement following bariatric/metabolic surgery. Diabetes Care. 2016;39(6):893–901.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Gerhard GS, Styer AM, Wood GC, et al. A role for fibroblast growth factor 19 and bile acids in diabetes remission after Roux-en-Y gastric bypass. Diabetes Care. 2013;36(7):1859–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. 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  CAS  Google Scholar 

  13. Ryan KK, Tremaroli V, Clemmensen C, et al. FXR is a molecular target for the effects of vertical sleeve gastrectomy. Nature. 2014;509(7499):183–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Wang H, Chen J, Hollister K, et al. Endogenous bile acids are ligands for the nuclear receptor FXR/BAR. Mol Cell. 1999;3(5):543–53.

    Article  CAS  PubMed  Google Scholar 

  15. Maruyama T, Miyamoto Y, Nakamura T, et al. Identification of membrane-type receptor for bile acids (M-BAR). Biochem Biophys Res Commun. 2002;298(5):714–9.

    Article  CAS  PubMed  Google Scholar 

  16. Kawamata Y, Fujii R, Hosoya M, et al. A G protein-coupled receptor responsive to bile acids. J Biol Chem. 2003;278(11):9435–40.

    Article  CAS  PubMed  Google Scholar 

  17. Houten SM, Watanabe M, Auwerx J. Endocrine functions of bile acids. EMBO J. 2006;25(7):1419–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Watanabe M, Houten SM, Wang L, et al. Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. J Clin Invest. 2004;113(10):1408–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Goodwin B, Jones SA, Price RR, et al. A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Mol Cell. 2000;6(3):517–26.

    Article  CAS  PubMed  Google Scholar 

  20. Lu TT, Makishima M, Repa JJ, et al. Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors. Mol Cell. 2000;6(3):507–15.

    Article  CAS  PubMed  Google Scholar 

  21. Alrefai WA, Gill RK. Bile acid transporters: structure, function, regulation and pathophysiological implications. Pharm Res. 2007;24(10):1803–23.

    Article  CAS  PubMed  Google Scholar 

  22. Watanabe M, Houten SM, Mataki C, et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature. 2006;439(7075):484–9.

    Article  CAS  PubMed  Google Scholar 

  23. Thomas C, Gioiello A, Noriega L, et al. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab. 2009;10(3):167–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Thomas C, Auwerx J, Schoonjans K. Bile acids and the membrane bile acid receptor TGR5—connecting nutrition and metabolism. Thyroid. 2008;18(2):167–74.

    Article  CAS  PubMed  Google Scholar 

  25. 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(3):e0122273.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. 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 Jul 21;6:7715.

    Article  CAS  PubMed  Google Scholar 

  27. 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(7):2341–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. 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(5):1360–71.

    Article  PubMed  Google Scholar 

  29. 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(2):482–8.

    Article  CAS  PubMed  Google Scholar 

  30. 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.

    Article  PubMed  Google Scholar 

  31. 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(11):1422–8.

    Article  CAS  PubMed  Google Scholar 

  32. 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(3 Pt 2):R618–25.

    CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  34. 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 Feb;44(2):340–8.

    Article  CAS  PubMed  Google Scholar 

  35. 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(6):1643–52.

    Article  PubMed  Google Scholar 

  36. Nakatani H, Kasama K, Oshiro T, et al. Serum bile acid along with plasma incretins and serum high-molecular weight adiponectin levels are increased after bariatric surgery. Metabolism. 2009;58(10):1400–7.

    Article  CAS  PubMed  Google Scholar 

  37. Patti ME, Houten SM, Bianco AC, et al. Serum bile acids are higher in humans with prior gastric bypass: potential contribution to improved glucose and lipid metabolism. Obesity (Silver Spring). 2009;17(9):1671–7.

    Article  CAS  Google Scholar 

  38. Fang S, Suh JM, Reilly SM, et al. Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance. Nat Med. 2015;21(2):159–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Roberts MS, Magnusson BM, Burczynski FJ, et al. Enterohepatic circulation: physiological, pharmacokinetic and clinical implications. Clin Pharmacokinet. 2002;41(10):751–90.

    Article  CAS  PubMed  Google Scholar 

  40. Nakahara M, Furuya N, Takagaki K, et al. Ileal bile acid-binding protein, functionally associated with the farnesoid X receptor or the ileal bile acid transporter, regulates bile acid activity in the small intestine. J Biol Chem. 2005;280(51):42283–9.

    Article  CAS  PubMed  Google Scholar 

  41. Pellicoro A, Faber KN. Review article: the function and regulation of proteins involved in bile salt biosynthesis and transport. Aliment Pharmacol Ther. 2007;26(Suppl 2):149–60.

    Article  CAS  PubMed  Google Scholar 

  42. Neimark E, Chen F, Li X, et al. Bile acid-induced negative feedback regulation of the human ileal bile acid transporter. Hepatology. 2004;40(1):149–56.

    Article  CAS  PubMed  Google Scholar 

  43. Lee H, Zhang Y, Lee FY, et al. FXR regulates organic solute transporters alpha and beta in the adrenal gland, kidney, and intestine. J Lipid Res. 2006;47(1):201–14.

    Article  CAS  PubMed  Google Scholar 

  44. Byrne JA, Strautnieks SS, Mieli-Vergani G, et al. The human bile salt export pump: characterization of substrate specificity and identification of inhibitors. Gastroenterology. 2002;123(5):1649–58.

    Article  CAS  PubMed  Google Scholar 

  45. Hallen S, Bjorquist A, Ostlund-Lindqvist AM, et al. Identification of a region of the ileal-type sodium/bile acid cotransporter interacting with a competitive bile acid transport inhibitor. Biochemistry. 2002;41(50):14916–24.

    Article  CAS  PubMed  Google Scholar 

  46. Balakrishnan A, Wring SA, Polli JE. Interaction of native bile acids with human apical sodium-dependent bile acid transporter (hASBT): influence of steroidal hydroxylation pattern and C-24 conjugation. Pharm Res. 2006;23(7):1451–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Kim RB, Leake B, Cvetkovic M, et al. Modulation by drugs of human hepatic sodium-dependent bile acid transporter (sodium taurocholate cotransporting polypeptide) activity. J Pharmacol Exp Ther. 1999;291(3):1204–9.

    CAS  PubMed  Google Scholar 

  48. Malinen MM, Ali I, Bezencon J, et al. Organic solute transporter OSTalpha/beta is overexpressed in nonalcoholic steatohepatitis and modulated by drugs associated with liver injury. Am J Physiol Gastrointest Liver Physiol. 2018;314(5):G597–g609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The authors thank Ms. Emiko Shibuya and Ms. Saori Shoji for their technical assistance, and the staff of 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 Japan Society for the Promotion of Science (Grant No. 17K10575).

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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

    Ichiro Ise, Naoki Tanaka, Hirofumi Imoto, Atsushi Kohyama, Kazuhiro Watanabe, Fuyuhiko Motoi, 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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Correspondence to Takeshi Naitoh.

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

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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 29, 1901–1910 (2019). https://doi.org/10.1007/s11695-019-03790-y

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