Role of Bile Acids in Metabolic Control

Trends in Endocrinology and Metabolism

Volumn 29, Issue 1, 2018, Pages 31-41

  Molinaro, Antonio ^a   Wahlström, Annika ^a   Marschall, Hanns Ulrich ^a  

^a UNIVERSITY OF GOTHENBURG   (Sweden)

Author keywords

bile acids; farnesoid X receptor; gut microbiota; non alcoholic fatty liver disease; non alcoholic steatohepatitis; obesity surgery; Takeda G protein coupled receptor 5

Indexed keywords

BILE ACID; CHENODEOXYCHOLIC ACID; COLESEVELAM; COLESTILAN; METFORMIN; CELL RECEPTOR; FARNESOID X-ACTIVATED RECEPTOR; G PROTEIN COUPLED RECEPTOR; GPBAR1 PROTEIN, HUMAN;

BARIATRIC SURGERY; BILE ACID METABOLISM; HUMAN; INTESTINE FLORA; METABOLIC REGULATION; NON INSULIN DEPENDENT DIABETES MELLITUS; NONALCOHOLIC FATTY LIVER; NONHUMAN; OBESITY; PATHOPHYSIOLOGY; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SIGNAL TRANSDUCTION; ANIMAL; METABOLISM; PHYSIOLOGY;

ANIMALS; BILE ACIDS AND SALTS; DIABETES MELLITUS, TYPE 2; GASTROINTESTINAL MICROBIOME; HUMANS; NON-ALCOHOLIC FATTY LIVER DISEASE; OBESITY; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RECEPTORS, G-PROTEIN-COUPLED;

EID: 85035237547     PISSN: 10432760     EISSN: 18793061     Source Type: Journal    
DOI: 10.1016/j.tem.2017.11.002     Document Type: Review

References (75)

1. Schaap, F.G., et al. Bile acid receptors as targets for drug development. Nat. Rev. Gastroenterol. Hepatol. 11 (2014), 55–67.
2. Wahlstrom, A., et al. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab. 24 (2016), 41–50.
3. Wahlstrom, A., et al. Induction of FXR signaling in germ-free mice colonized with a human microbiota. J. Lipid Res. 58 (2016), 412–419.
4. Sayin, S.I., et al. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab. 17 (2013), 225–235.
5. Sato, H., et al. Novel potent and selective bile acid derivatives as TGR5 agonists: biological screening, structure-activity relationships, and molecular modeling studies. J. Med. Chem. 51 (2008), 1831–1841.
6. Flegal, K.M., et al. Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. J. Am. Med. Assoc. 309 (2013), 71–82.
7. Willyard, C., Heritability: the family roots of obesity. Nature 508 (2014), S58–60.
8. Vassileva, G., et al. Targeted deletion of Gpbar1 protects mice from cholesterol gallstone formation. Biochem. J. 398 (2006), 423–430.
9. Maruyama, T., et al. Targeted disruption of G protein-coupled bile acid receptor 1 (Gpbar1/M-Bar) in mice. J. Endocrinol. 191 (2006), 197–205.
10. Watanabe, M., et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 439 (2006), 484–489.
11. Kumar, D.P., et al. Activation of transmembrane bile acid receptor TGR5 modulates pancreatic islet alpha cells to promote glucose homeostasis. J. Biol. Chem. 291 (2016), 6626–6640.
12. Thomas, C., et al. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab. 10 (2009), 167–177.
13. Trabelsi, M.S., et al. Farnesoid X receptor inhibits glucagon-like peptide-1 production by enteroendocrine L cells. Nat. Commun., 6, 2015, 7629.
14. Kim, K.H., et al. Hepatic FXR/SHP axis modulates systemic glucose and fatty acid homeostasis in aged mice. Hepatology 66 (2017), 498–509.
15. Lambert, G., et al. The farnesoid X-receptor is an essential regulator of cholesterol homeostasis. J. Biol. Chem. 278 (2003), 2563–2570.
16. Parseus, A., et al. Microbiota-induced obesity requires farnesoid X receptor. Gut 66 (2017), 429–437.
17. Prawitt, J., et al. Farnesoid X receptor deficiency improves glucose homeostasis in mouse models of obesity. Diabetes 60 (2011), 1861–1871.
18. Zhang, Y., et al. Identification of novel pathways that control farnesoid X receptor-mediated hypocholesterolemia. J. Biol. Chem. 285 (2010), 3035–3043.
19. Schmitt, J., et al. Protective effects of farnesoid X receptor (FXR) on hepatic lipid accumulation are mediated by hepatic FXR and independent of intestinal FGF15 signal. Liver Int. 35 (2015), 1133–1144.
20. Jiang, C., et al. Intestine-selective farnesoid X receptor inhibition improves obesity-related metabolic dysfunction. Nat. Commun., 6, 2015, 10166.
21. Li, F., et al. Microbiome remodelling leads to inhibition of intestinal farnesoid X receptor signalling and decreased obesity. Nat. Commun., 4, 2013, 2384.
22. de Boer, J.F., et al. Intestinal farnesoid X receptor controls transintestinal cholesterol excretion in mice. Gastroenterology, 152, 2017 1126–1138 e6.
23. Fang, S., et al. Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance. Nat. Med. 21 (2015), 159–165.
24. Chavez-Talavera, O., et al. Bile Acid control of metabolism and inflammation in obesity, type 2 diabetes, dyslipidemia, and nonalcoholic fatty liver disease. Gastroenterology, 152, 2017 1679–1694 e3.
25. Kaur, A., et al. Loss of Cyp8b1 improves glucose homeostasis by increasing GLP-1. Diabetes 64 (2015), 1168–1179.
26. Haeusler, R.A., et al. Impaired generation of 12-hydroxylated bile acids links hepatic insulin signaling with dyslipidemia. Cell Metab. 15 (2012), 65–74.
27. Biemann, R., et al. Serum bile acids and GLP-1 decrease following telemetric induced weight loss: results of a randomized controlled trial. Sci. Rep., 6, 2016, 30173.
28. Broeders, E.P., et al. The bile acid chenodeoxycholic acid increases human brown adipose tissue activity. Cell Metab. 22 (2015), 418–426.
29. Hansen, M., et al. Bile acid sequestrants for glycemic control in patients with type 2 diabetes: a systematic review with meta-analysis of randomized controlled trials. J. Diabetes Complications 31 (2017), 918–927.
30. Beysen, C., 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 55 (2012), 432–442.
31. Wu, H., et al. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat. Med. 23 (2017), 850–858.
32. Caesar, R., et al. Crosstalk between gut microbiota and dietary lipids aggravates WAT inflammation through TLR signaling. Cell Metab. 22 (2015), 658–668.
33. Ridaura, V.K., et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science, 341, 2013 1241214.
34. Tremaroli, V., et al. Roux-en-Y gastric bypass and vertical banded gastroplasty induce long-term changes on the human gut microbiome contributing to fat mass regulation. Cell Metab. 22 (2015), 228–238.
35. Sjostrom, L., et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N. Engl. J. Med. 351 (2004), 2683–2693.
36. Isbell, J.M., et al. The importance of caloric restriction in the early improvements in insulin sensitivity after Roux-en-Y gastric bypass surgery. Diabetes Care 33 (2010), 1438–1442.
37. Evers, S.S., et al. The physiology and molecular underpinnings of the effects of bariatric surgery on obesity and diabetes. Annu. Rev. Physiol. 79 (2017), 313–334.
38. Albaugh, V.L., et al. Bile acids and bariatric surgery. Mol. Aspects Med. 56 (2017), 75–89.
39. Albaugh, V.L., et al. Early increases in bile acids post Roux-en-Y gastric bypass are driven by insulin-sensitizing, secondary bile acids. J. Clin. Endocrinol. Metab. 100 (2015), E1225–E1233.
40. Stefater, M.A., et al. All bariatric surgeries are not created equal: insights from mechanistic comparisons. Endocr. Rev. 33 (2012), 595–622.
41. Marschall, H.U., et al. Ursodeoxycholic acid for treatment of fatty liver disease and dyslipidemia in morbidly obese patients. Dig. Dis. 29 (2011), 117–118.
42. Mueller, M., et al. Ursodeoxycholic acid exerts farnesoid X receptor-antagonistic effects on bile acid and lipid metabolism in morbid obesity. J. Hepatol. 62 (2015), 1398–1404.
43. Khan, F.H., Kohli, R., Bariatric surgery: the rise and fall of bile acids. Surg. Obes. Relat. Dis. 12 (2016), 770–771.
44. van Nierop, F.S., et al. Effects of acute dietary weight loss on postprandial plasma bile acid responses in obese insulin resistant subjects. Clin. Nutr. 36 (2016), 1615–1620.
45. Kars, M., et al. Tauroursodeoxycholic acid may improve liver and muscle but not adipose tissue insulin sensitivity in obese men and women. Diabetes 59 (2010), 1899–1905.
46. Cummings, B.P., et al. Vertical sleeve gastrectomy improves glucose and lipid metabolism and delays diabetes onset in UCD-T2DM rats. Endocrinology 153 (2012), 3620–3632.
47. Palleja, A., et al. Roux-en-Y gastric bypass surgery of morbidly obese patients induces swift and persistent changes of the individual gut microbiota. Genome Med., 8, 2016, 67.
48. Ryan, K.K., et al. FXR is a molecular target for the effects of vertical sleeve gastrectomy. Nature 509 (2014), 183–188.
49. Flynn, C.R., et al. Bile diversion to the distal small intestine has comparable metabolic benefits to bariatric surgery. Nat. Commun., 6, 2015, 7715.
50. McGavigan, A.K., et al. TGR5 contributes to glucoregulatory improvements after vertical sleeve gastrectomy in mice. Gut 66 (2017), 226–234.
51. Ding, L., et al. Vertical sleeve gastrectomy activates GPBAR-1/TGR5 to sustain weight loss, improve fatty liver, and remit insulin resistance in mice. Hepatology 64 (2016), 760–773.
52. Pathak, P., et al. Farnesoid X receptor induces Takeda G-protein receptor 5 cross-talk to regulate bile acid synthesis and hepatic metabolism. J. Biol. Chem. 292 (2017), 11055–11069.
53. Rinella, M.E., Nonalcoholic fatty liver disease: a systematic review. J. Am. Med. Assoc. 313 (2015), 2263–2273.
54. Loomba, R., Sanyal, A.J., The global NAFLD epidemic. Nat. Rev. Gastroenterol. Hepatol 10 (2013), 686–690.
55. Arab, J.P., et al. Bile acids and nonalcoholic fatty liver disease: molecular insights and therapeutic perspectives. Hepatology 65 (2017), 350–362.
56. Bechmann, L.P., et al. Free fatty acids repress small heterodimer partner (SHP) activation and adiponectin counteracts bile acid-induced liver injury in superobese patients with nonalcoholic steatohepatitis. Hepatology 57 (2013), 1394–1406.
57. Jahnel, J., et al. Serum bile acid levels in children with nonalcoholic fatty liver disease. J. Pediatr. Gastroenterol. Nutr. 61 (2015), 85–90.
58. Puri, P., et al. The presence and severity of nonalcoholic steatohepatitis is associated with specific changes in circulating bile acids. Hepatology, 2017, 10.1002/hep.29359.
59. Mouzaki, M., et al. Bile acids and dysbiosis in non-alcoholic fatty liver disease. PLoS One, 11, 2016, e0151829.
60. Min, H.K., et al. Increased hepatic synthesis and dysregulation of cholesterol metabolism is associated with the severity of nonalcoholic fatty liver disease. Cell Metab. 15 (2012), 665–674.
61. Jiao, N., et al. Suppressed hepatic bile acid signalling despite elevated production of primary and secondary bile acids in NAFLD. Gut, 2017, 10.1136/gutjnl-2017-314307.
62. Schnabl, B., Brenner, D.A., Interactions between the intestinal microbiome and liver diseases. Gastroenterology 146 (2014), 1513–1524.
63. Moschen, A.R., et al. Non-alcoholic steatohepatitis: a microbiota-driven disease. Trends Endocrinol. Metab. 24 (2013), 537–545.
64. Aranha, M.M., et al. Bile acid levels are increased in the liver of patients with steatohepatitis. Eur. J. Gastroenterol. Hepatol. 20 (2008), 519–525.
65. Lake, A.D., et al. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease. Toxicol. Appl. Pharmacol. 268 (2013), 132–140.
66. Yang, Z.X., et al. Effects of nuclear receptor FXR on the regulation of liver lipid metabolism in patients with non-alcoholic fatty liver disease. Hepatol. Int. 4 (2010), 741–748.
67. Janssen, A.W.F., et al. Modulation of the gut microbiota impacts nonalcoholic fatty liver disease: a potential role for bile acids. J. Lipid Res. 58 (2017), 1399–1416.
68. Zhang, L., et al. Farnesoid X receptor signaling shapes the gut microbiota and controls hepatic lipid metabolism. mSystems, 2016, 1.
69. Loomba, R., et al. Gut microbiome-based metagenomic signature for non-invasive detection of advanced fibrosis in human nonalcoholic fatty liver disease. Cell Metab., 25, 2017 1054–1062 e5.
70. Graffner, H., et al. The ileal bile acid transporter inhibitor A4250 decreases serum bile acids by interrupting the enterohepatic circulation. Aliment Pharmacol. Ther. 43 (2016), 303–310.
71. Rao, A., et al. Inhibition of ileal bile acid uptake protects against nonalcoholic fatty liver disease in high-fat diet-fed mice. Sci. Transl. Med., 8, 2016 357ra122.
72. Mudaliar, S., et al. Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology, 145, 2013 574–582 e1.
73. Neuschwander-Tetri, B.A., et al. Farnesoid X. nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet 385 (2015), 956–965.
74. Pencek, R., et al. Effects of obeticholic acid on lipoprotein metabolism in healthy volunteers. Diabetes Obes. Metab. 18 (2016), 936–940.
75. Feaver, R.E., et al. Development of an in vitro human liver system for interrogating nonalcoholic steatohepatitis. JCI Insight, 1, 2016, e90954.