Mechanisms of Action of Surgical Interventions on Weight-Related Diseases: the Potential Role of Bile Acids

Obesity Surgery

Volumn 27, Issue 3, 2017, Pages 826-836

  Mazidi, Mohsen ^a,b   de Caravatto, Pedro Paulo P ^c   Speakman, John R ^a,d   Cohen, Ricardo V ^c  

^a INSTITUTE OF GENETICS AND DEVELOPMENTAL BIOLOGY   (China)

^b UNIVERSITY OF CHINESE ACADEMY OF SCIENCES   (China)

^c Oswaldo Cruz German Hospital   (Brazil)

^d UNIVERSITY OF ABERDEEN   (United Kingdom)

Author keywords

Bile acids; Mechanisms of action; Metabolic surgery; RYGB; Surgery of weight related diseases

Indexed keywords

BILE ACID; BILE ACID SEQUESTRANT; FARNESOID X RECEPTOR; FIBROBLAST GROWTH FACTOR 19; G PROTEIN COUPLED BILE ACID RECEPTOR 5; GLUCAGON LIKE PEPTIDE 1; RECEPTOR; UNCLASSIFIED DRUG; FGF19 PROTEIN, HUMAN; FIBROBLAST GROWTH FACTOR;

BILE ACID BLOOD LEVEL; BILE ACID METABOLISM; BILE ACID SYNTHESIS; BODY WEIGHT DISORDER; ENERGY EXPENDITURE; ENERGY METABOLISM; GLUCOSE METABOLISM; HUMAN; INSULIN SENSITIVITY; INTESTINE; L CELL LINE; LIPID METABOLISM; METABOLIC DISORDER; METABOLIC PARAMETERS; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PRIORITY JOURNAL; PROTEIN EXPRESSION; REMISSION; REVIEW; ROUX-EN-Y GASTRIC BYPASS; WEIGHT REDUCTION; BLOOD; COMPLICATION; GASTRIC BYPASS SURGERY; INSULIN RESISTANCE; MORBID OBESITY; PHYSIOLOGY; PROCEDURES;

BILE ACIDS AND SALTS; DIABETES MELLITUS, TYPE 2; FIBROBLAST GROWTH FACTORS; GASTRIC BYPASS; GLUCAGON-LIKE PEPTIDE 1; HUMANS; INSULIN RESISTANCE; OBESITY, MORBID;

EID: 85009473301     PISSN: 09608923     EISSN: 17080428     Source Type: Journal    
DOI: 10.1007/s11695-017-2549-1     Document Type: Review

References (118)

1. Chang SH, Stoll CR, Song J, et al. The effectiveness and risks of bariatric surgery: an updated systematic review and meta-analysis, 2003-2012. JAMA surgery. 2014;149(3):275–87.
2. Clifton PM. Bariatric surgery: results in obesity and effects on metabolic parameters. Curr Opin Lipidol. 2011;22(1):1–5.
3. Eldar S, Heneghan HM, Brethauer SA, et al. Bariatric surgery for treatment of obesity. Int J Obes. 2005;35(Suppl 3):S16–21.
4. Fallahi-Shahabad S, Mazidi M, Tavasoli A, et al. Metabolic improvement of morbid obese patients following Roux-en-Y gastric bypass surgery: a prospective study in Mashhad. Iran Indian J Gastroenterol. 2016;35(3):195–200.
5. Isbell JM, Tamboli RA, Hansen EN, et al. The importance of caloric restriction in the early improvements in insulin sensitivity after Roux-en-Y gastric bypass surgery. Diabetes Care. 2010;33(7):1438–42.
6. Hajnal A, Kovacs P, Ahmed T, et al. Gastric bypass surgery alters behavioral and neural taste functions for sweet taste in obese rats. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2010;299(4):G967–G79.
7. Thanos PK, Subrize M, Delis F, et al. Gastric bypass increases ethanol and water consumption in diet-induced obese rats. Obes Surg. 2012;22(12):1884–92.
8. Roberts RE, Alaghband-Zadeh J, Le Roux CW. The role of bile acids in gut-hormone-induced weight loss after bariatric surgery: implications for appetite control and diabetes. Handbook of behavior, food and nutrition. Berlin: Springer; 2011. p. 1317–30.
9. Verdich C, Flint A, Gutzwiller JP, et al. A meta-analysis of the effect of glucagon-like peptide-1 (7-36) amide on ad libitum energy intake in humans. J Clin Endocrinol Metab. 2001;86(9):4382–9.
10. Mohsen Mazidi EK, Peyman rezaie, Ferns GA. Treatment with GLP1 receptor agonists reduce serum CRP concentrations in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. Journal of Diabetes and Its Complications. 2016.
11. Holst JJ, Deacon CF. Inhibition of the activity of dipeptidyl-peptidase IV as a treatment for type 2 diabetes. Diabetes. 1998;47(11):1663–70.
12. Deacon CF, Holst JJ. Dipeptidyl peptidase IV inhibitors: a promising new therapeutic approach for the management of type 2 diabetes. Int J Biochem Cell Biol. 2006;38(5–6):831–44.
13. Kindel TL, Yoder SM, Seeley RJ, et al. Duodenal-jejunal exclusion improves glucose tolerance in the diabetic, Goto-Kakizaki rat by a GLP-1 receptor-mediated mechanism. J Gastrointest Surg. 2009;13(10):1762–72.
14. Patriti A, Aisa MC, Annetti C, et al. How the hindgut can cure type 2 diabetes. Ileal transposition improves glucose metabolism and beta-cell function in Goto-Kakizaki rats through an enhanced proglucagon gene expression and L-cell number. Surgery. 2007;142(1):74–85.
15. Houten SM, Watanabe M, Auwerx J. Endocrine functions of bile acids. EMBO J. 2006;25(7):1419–25.
16. 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.
17. Pournaras DJ, Osborne A, Hawkins SC, et al. Remission of type 2 diabetes after gastric bypass and banding: mechanisms and 2 year outcomes. Ann Surg. 2010;252(6):966–71.
18. le Roux CW, Welbourn R, Werling M, et al. Gut hormones as mediators of appetite and weight loss after Roux-en-Y gastric bypass. Ann Surg. 2007;246(5):780–5.
19. Pories WJ, Swanson MS, MacDonald KG, et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg. 1995;222(3):339.
20. Neary NM, Small CJ, Druce MR, et al. Peptide YY3–36 and glucagon-like peptide-17–36 inhibit food intake additively. Endocrinology. 2005;146(12):5120–7.
21. Chiang JY. Bile acids: regulation of synthesis. J Lipid Res. 2009;50(10):1955–66.
22. Ma H, Patti ME. Bile acids, obesity, and the metabolic syndrome. Best Pract Res Clin Gastroenterol. 2014;28(4):573–83.
23. Hofmann AF. The enterohepatic circulation of bile acids in mammals: form and functions. Frontiers in bioscience (Landmark edition). 2008;14:2584–98.
24. 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.
25. Kir S, Beddow SA, Samuel VT, et al. FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis. Science (New York, NY). 2011;331(6024):1621–4.
26. Lundåsen T, Gälman C, Angelin B, et al. Circulating intestinal fibroblast growth factor 19 has a pronounced diurnal variation and modulates hepatic bile acid synthesis in man. J Intern Med. 2006;260(6):530–6.
27. Wu A-L, Coulter S, Liddle C, et al. FGF19 regulates cell proliferation, glucose and bile acid metabolism via FGFR4-dependent and independent pathways. PLoS One. 2011;6(3):e17868.
28. 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.
29. Taoka H, Yokoyama Y, Morimoto K, et al. Role of bile acids in the regulation of the metabolic pathways. World J Diabetes. 2016;7(13):260–70.
30. Vanwijngaerden YM, Wauters J, Langouche L, et al. Critical illness evokes elevated circulating bile acids related to altered hepatic transporter and nuclear receptor expression. Hepatology. 2011;54(5):1741–52.
31. Zollner G, Wagner M, Moustafa T, et al. Coordinated induction of bile acid detoxification and alternative elimination in mice: role of FXR-regulated organic solute transporter-α/β in the adaptive response to bile acids. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2006;290(5):G923–G32.
32. Yuan Z, Li K. The role of farnesoid X receptor in cholestasis. J Dig Dis. 2016;6 doi:10.1111/1751-2980.12378.
33. Hanniman EA, Lambert G, McCarthy TC, et al. Loss of functional farnesoid X receptor increases atherosclerotic lesions in apolipoprotein E-deficient mice. J Lipid Res. 2005;46(12):2595–604.
34. Hartman HB, Gardell SJ, Petucci CJ, et al. Activation of farnesoid X receptor prevents atherosclerotic lesion formation in LDLR−/− and apoE−/− mice. J Lipid Res. 2009;50(6):1090–100.
35. Lambert G, Amar MJ, Guo G, et al. The farnesoid X-receptor is an essential regulator of cholesterol homeostasis. J Biol Chem. 2003;278(4):2563–70.
36. Mencarelli A, Renga B, Distrutti E, et al. Antiatherosclerotic effect of farnesoid X receptor. Am J Phys Heart Circ Phys. 2009;296(2):H272–H81.
37. Zhang Y, Wang X, Vales C, et al. FXR deficiency causes reduced atherosclerosis in Ldlr−/− mice. Arterioscler Thromb Vasc Biol. 2006;26(10):2316–21.
38. 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.
39. Katsuma S, Hirasawa A, Tsujimoto G. Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1. Biochem Biophys Res Commun. 2005;329(1):386–90.
40. Thomas C, Gioiello A, Noriega L, et al. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab. 2009;10(3):167–77.
41. Sato H, Genet C, Strehle A, et al. Anti-hyperglycemic activity of a TGR5 agonist isolated from Olea europaea. Biochem Biophys Res Commun. 2007;362(4):793–8.
42. Cipriani S, Mencarelli A, Palladino G, et al. FXR activation reverses insulin resistance and lipid abnormalities and protects against liver steatosis in Zucker (fa/fa) obese rats. J Lipid Res. 2010;51(4):771–84.
43. Ma K, Saha PK, Chan L, et al. Farnesoid X receptor is essential for normal glucose homeostasis. J Clin Invest. 2006;116(4):1102–9.
44. Zhang Y, Lee FY, Barrera G, et al. Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice. Proc Natl Acad Sci U S A. 2006;103(4):1006–11.
45. Pournaras DJ, Glicksman C, Vincent RP, et al. The role of bile after Roux-en-Y gastric bypass in promoting weight loss and improving glycaemic control. Endocrinology. 2012;153(8):3613–9.
46. Shaham O, Wei R, Wang TJ, et al. Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity. Mol Syst Biol. 2008;4(1):214.
47. Dent P, Fang Y, Gupta S, et al. Conjugated bile acids promote ERK1/2 and AKT activation via a pertussis toxin–sensitive mechanism in murine and human hepatocytes. Hepatology. 2005;42(6):1291–9.
48. Han SI, Studer E, Gupta S, et al. Bile acids enhance the activity of the insulin receptor and glycogen synthase in primary rodent hepatocytes. Hepatology. 2004;39(2):456–63.
49. Parker H, Wallis K, Le Roux C, et al. Molecular mechanisms underlying bile acid-stimulated glucagon-like peptide-1 secretion. Br J Pharmacol. 2012;165(2):414–23.
50. Adrian TE, Gariballa S, Parekh K, et al. Rectal taurocholate increases L cell and insulin secretion, and decreases blood glucose and food intake in obese type 2 diabetic volunteers. Diabetologia. 2012;55(9):2343–7.
51. Vassiliou EK, Gonzalez A, Garcia C, et al. Oleic acid and peanut oil high in oleic acid reverse the inhibitory effect of insulin production of the inflammatory cytokine TNF-alpha both in vitro and in vivo systems. Lipids Health Dis. 2009;8:25.
52. 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.
53. Ockenga J, Valentini L, Schuetz T, et al. Plasma bile acids are associated with energy expenditure and thyroid function in humans. The Journal of Clinical Endocrinology & Metabolism. 2011;97(2):535–42.
54. Glicksman C, Pournaras D, Wright M, et al. Postprandial plasma bile acid responses in normal weight and obese subjects. Ann Clin Biochem. 2010;47(5):482–4.
55. Ahmad N, Pfalzer A, Kaplan L. Roux-en-Y gastric bypass normalizes the blunted postprandial bile acid excursion associated with obesity. Int J Obes. 2013;37(12):1553–9.
56. Sato H, Macchiarulo A, Thomas C, et al. Novel potent and selective bile acid derivatives as TGR5 agonists: biological screening, structure−activity relationships, and molecular modeling studies. J Med Chem. 2008;51(6):1831–41.
57. Das SK, Roberts SB, McCrory MA, et al. Long-term changes in energy expenditure and body composition after massive weight loss induced by gastric bypass surgery. Am J Clin Nutr. 2003;78(1):22–30.
58. Faria SL, Faria OP, de Almeida CM, et al. Diet-induced thermogenesis and respiratory quotient after Roux-en-Y gastric bypass. Surg Obes Relat Dis. 2012;8(6):797–802.
59. Thivel D, Brakonieki K, Duche P, et al. Surgical weight loss: impact on energy expenditure. Obes Surg. 2013;23(2):255–66.
60. Wilms B, Ernst B, Thurnheer M, et al. Increased thermic effect of food after gastric bypass surgery. Obesity reviews: an official journal of the International Association for the Study of Obesity. 2012;13(Suppl 2):125.
61. Mason EE, Ito C. Gastric bypass in obesity. Surg Clin North Am. 1967;47(6):1345–51.
62. Pories WJ, Flickinger EG, Meelheim D, et al. The effectiveness of gastric bypass over gastric partition in morbid obesity: consequence of distal gastric and duodenal exclusion. Ann Surg. 1982;196(4):389–99.
63. Brolin RE, Kenler HA, Gorman JH, et al. Long-limb gastric bypass in the superobese. A prospective randomized study. Ann Surg. 1992;215(4):387–95.
64. Freeman JB, Kotlarewsky M, Phoenix C. Weight loss after extended gastric bypass. Obes Surg. 1997;7(4):337–44.
65. Scopinaro N, Gianetta E, Adami GF, et al. Biliopancreatic diversion for obesity at eighteen years. Surgery. 1996;119(3):261–8.
66. Pinheiro JS, Schiavon CA, Pereira PB, et al. Long-long limb Roux-en-Y gastric bypass is more efficacious in treatment of type 2 diabetes and lipid disorders in super-obese patients. Surg Obes Relat Dis. 2008;4(4):521–5.
67. MacLean LD, Rhode BM, Nohr CW. Long- or short-limb gastric bypass? J Gastrointest Surg. 2001;5(5):525–30.
68. Ciovica R, Takata M, Vittinghoff E, et al. The impact of roux limb length on weight loss after gastric bypass. Obes Surg. 2008;18(1):5–10.
69. Feng JJ, Gagner M, Pomp A, et al. Effect of standard vs extended Roux limb length on weight loss outcomes after laparoscopic Roux-en-Y gastric bypass. Surg Endosc. 2003;17(7):1055–60.
70. Christou NV, Look D, Maclean LD. Weight gain after short- and long-limb gastric bypass in patients followed for longer than 10 years. Ann Surg. 2006;244(5):734–40.
71. Sugerman HJKJ, DeMaria EJ. Conversion of proximal to distal bypass for failed gastric bypass for superobesity. J Gastrointest Surg. 1997;1:517–26.
72. Brolin RECR. Adding malabsorption for weight loss failure after gastric bypass. SurgEndosc. 2007;21:1924–6.
73. Nelson WKFJ, Houghton SG, et al. The malabsorptive very, very long limb Roux-en-Y gastric bypass for super obesity: results in 257 patients. Surgery. 2006;140:517–23.
74. McConnell DBORR, Deveney CW. Common channel length predicts outcomes of biliopancreatic diversion alone and with the duodenal switch surgery. Am J Surg. 2005;189:536–40.
75. Brolin RELL, Kelner HA, et al. Malabsorptive gastric bypass in patients with superobesity. J Gastrointest Surgery. 2002;6:195–205.
76. Ionut V, Burch M, Youdim A, et al. Gastrointestinal hormones and bariatric surgery-induced weight loss. Obesity. 2013;21(6):1093–103.
77. 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. 2009;17(9):1671–7.
78. Steinert RE, Peterli R, Keller S, et al. Bile acids and gut peptide secretion after bariatric surgery: a 1-year prospective randomized pilot trial. Obesity. 2013;21(12):E660–E8.
79. Scholtz S, Miras AD, Chhina N, et al. Obese patients after gastric bypass surgery have lower brain-hedonic responses to food than after gastric banding. Gut. 2014;63(6):891–902.
80. Werling M, Vincent RP, Cross GF, et al. Enhanced fasting and post-prandial plasma bile acid responses after Roux-en-Y gastric bypass surgery. Scand J Gastroenterol. 2013;48(11):1257–64.
81. Kohli R, Bradley D, Setchell KD, et al. Weight loss induced by Roux-en-Y gastric bypass but not laparoscopic adjustable gastric banding increases circulating bile acids. J Clin Endocrinol Metab. 2013;98(4):E708–12.
82. Ashrafian H, Li JV, Spagou K, et al. Bariatric surgery modulates circulating and cardiac metabolites. J Proteome Res. 2014;13(2):570–80.
83. Jansen PL, van Werven J, Aarts E, et al. Alterations of hormonally active fibroblast growth factors after Roux-en-Y gastric bypass surgery. Dig Dis. 2011;29(1):48–51.
84. Simonen M, Dali-Youcef N, Kaminska D, et al. Conjugated bile acids associate with altered rates of glucose and lipid oxidation after Roux-en-Y gastric bypass. Obes Surg. 2012;22(9):1473–80.
85. Dirksen C, Jørgensen N, Bojsen-Møller K, et al. Gut hormones, early dumping and resting energy expenditure in patients with good and poor weight loss response after Roux-en-Y gastric bypass. Int J Obes. 2013;37(11):1452–9.
86. 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.
87. Haluzikova D, Lacinova Z, Kavalkova P, et al. Laparoscopic sleeve gastrectomy differentially affects serum concentrations of FGF-19 and FGF-21 in morbidly obese subjects. Obesity (Silver Spring). 2013 Jul;21(7):1335–42.
88. Korner J, Inabnet W, Febres G, et al. Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass. Int J Obes. 2009;33(7):786–95.
89. Laferrère B, Heshka S, Wang K, et al. Incretin levels and effect are markedly enhanced 1 month after Roux-en-Y gastric bypass surgery in obese patients with type 2 diabetes. Diabetes Care. 2007;30(7):1709–16.
90. Morínigo R, Moizé V, Musri M, et al. Glucagon-like peptide-1, peptide YY, hunger, and satiety after gastric bypass surgery in morbidly obese subjects. The Journal of Clinical Endocrinology & Metabolism. 2006;91(5):1735–40.
91. Vidal J, Nicolau J, Romero F, et al. Long-term effects of Roux-en-Y gastric bypass surgery on plasma glucagon-like peptide-1 and islet function in morbidly obese subjects. The Journal of Clinical Endocrinology & Metabolism. 2009;94(3):884–91.
92. Nestoridi E, Kvas S, Kucharczyk J, et al. Resting energy expenditure and energetic cost of feeding are augmented after Roux-en-Y gastric bypass in obese mice. Endocrinology. 2012;153(5):2234–44.
93. Plum L, Ahmed L, Febres G, et al. Comparison of glucostatic parameters after hypocaloric diet or bariatric surgery and equivalent weight loss. Obesity. 2011;19(11):2149–57.
94. Stylopoulos N, Zhang XB, Brownell A-L, et al. W1854 Roux-en-Y gastric bypass activates brown adipose tissue and increases energy expenditure in obese mice. Gastroenterology. 2010;138(5):S-754.
95. 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. Metab Clin Exp. 2009;58(10):1400–7.
96. Liaset B, Hao Q, Jørgensen H, et al. Nutritional regulation of bile acid metabolism is associated with improved pathological characteristics of the metabolic syndrome. J Biol Chem. 2011;286(32):28382–95.
97. Mencarelli A, Renga B, D’Amore C, et al. Dissociation of intestinal and hepatic activities of FXR and LXRα supports metabolic effects of terminal ileum interposition in rodents. Diabetes. 2013;62(10):3384–93.
98. Pournaras D, le Roux C. Are bile acids the new gut hormones? Lessons from weight loss surgery models. Endocrinology. 2013;154(7):2255–6.
99. 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.
100. Dhurandhar NV, Schoeller D, Brown AW, et al. Energy balance measurement: when something is not better than nothing. Int J Obes. 2015 Jul;39(7):1109–13.
101. 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.
102. Woelnerhanssen B, Peterli R, Steinert RE, et al. Effects of postbariatric surgery weight loss on adipokines and metabolic parameters: comparison of laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy—a prospective randomized trial. Surg Obes Relat Dis. 2011;7(5):561–8.
103. Zhang Y, Edwards PA. FXR signaling in metabolic disease. FEBS Lett. 2008;582(1):10–8.
104. Kohli R, Bradley D, Setchell KD, et al. Weight loss induced by Roux-en-Y gastric bypass but not laparoscopic adjustable gastric banding increases circulating bile acids. The Journal of Clinical Endocrinology & Metabolism. 2013;98(4):E708–E12.
105. Insull Jr W. Clinical utility of bile acid sequestrants in the treatment of dyslipidemia: a scientific review. South Med J. 2006;99(3):257–74.
106. Beysen C, Murphy E, Deines K, et al. Effect of bile acid sequestrants on glucose metabolism, hepatic de novo lipogenesis, and cholesterol and bile acid kinetics in type 2 diabetes: a randomised controlled study. Diabetologia. 2012;55(2):432–42.
107. Fonseca VA, Rosenstock J, Wang AC, et al. Colesevelam HCl improves glycemic control and reduces LDL cholesterol in patients with inadequately controlled type 2 diabetes on sulfonylurea-based therapy. Diabetes Care. 2008;31(8):1479–84.
108. Goldberg RB, Fonseca VA, Truitt KE, et al. Efficacy and safety of colesevelam in patients with type 2 diabetes mellitus and inadequate glycemic control receiving insulin-based therapy. Arch Intern Med. 2008;168(14):1531–40.
109. Shang Q, Saumoy M, Holst JJ, et al. Colesevelam improves insulin resistance in a diet-induced obesity (F-DIO) rat model by increasing the release of GLP-1. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2010;298(3):G419–G24.
110. Suzuki T, Oba K, Igari Y, et al. Colestimide lowers plasma glucose levels and increases plasma glucagon-like PEPTIDE-1 (7-36) levels in patients with type 2 diabetes mellitus complicated by hypercholesterolemia. Journal of Nippon Medical School. 2007;74(5):338–43.
111. Watanabe M, Morimoto K, Houten SM, et al. Bile acid binding resin improves metabolic control through the induction of energy expenditure. PLoS One. 2012;7(8):e38286.
112. Harach T, Pols TW, Nomura M, et al. TGR5 potentiates GLP-1 secretion in response to anionic exchange resins. Scientific reports. 2012;2
113. Matsubara T, Li F, Gonzalez FJ. FXR signaling in the enterohepatic system. Mol Cell Endocrinol. 2013;368(1):17–29.
114. Duboc H, Taché Y, Hofmann AF. The bile acid TGR5 membrane receptor: from basic research to clinical application. Dig Liver Dis. 2014;46(4):302–12.
115. Stepanov V, Stankov K, Mikov M. The bile acid membrane receptor TGR5: a novel pharmacological target in metabolic, inflammatory and neoplastic disorders. Journal of Receptors and Signal Transduction. 2013;33(4):213–23.
116. Staels B, Kuipers F. Bile acid sequestrants and the treatment of type 2 diabetes mellitus. Drugs. 2007;67(10):1383–92.
117. Brufau G, Bahr MJ, Staels B, et al. Plasma bile acids are not associated with energy metabolism in humans. Nutrition & metabolism. 2010;7(1):1.
118. Brufau G, Stellaard F, Prado K, et al. Improved glycemic control with colesevelam treatment in patients with type 2 diabetes is not directly associated with changes in bile acid metabolism. Hepatology. 2010;52(4):1455–64.