Advertisement

Changes in Bile Acid Metabolism, Transport, and Signaling as Central Drivers for Metabolic Improvements After Bariatric Surgery

  • Matthew G. Browning
  • Bernardo M. Pessoa
  • Jad Khoraki
  • Guilherme M. CamposEmail author
Obesity Treatment (CM Apovian, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Obesity Treatment

Abstract

Purpose of Review

We review current evidence regarding changes in bile acid (BA) metabolism, transport, and signaling after bariatric surgery and how these might bolster fat mass loss and energy expenditure to promote improvements in type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD).

Recent Findings

The two most common bariatric techniques, Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), increase the size and alter the composition of the circulating BA pool that may then impact energy metabolism through altered activities of BA targets in the many tissues perfused by systemic blood. Recent reports in human patients indicate that gene expression of the major BA target, the farnesoid X receptor (FXR), is increased in the liver but decreased in the small intestine after RYGB. In contrast, intestinal expression of the transmembrane G protein-coupled BA receptor (TGR5) is upregulated after surgery. Despite these apparent conflicting changes in receptor transcription, changes in BAs after both RYGB and VSG are associated with elevated postprandial systemic levels of fibroblast growth factor 19 (from FXR activation) and glucagon-like peptide 1 (from TGR5 activation). These signaling activities are presumed to support fat mass loss and related metabolic benefits of bariatric surgery, and this supposition is in agreement with findings from rodent models of RYGB and VSG. However, inter-species differences in BA physiology limit direct translation and mechanistic understanding of how changes in individual BA species contribute to post-operative improvements of T2D and NAFLD in humans. Thus, details of all these changes and their influences on BAs’ biological actions are still under scrutiny.

Summary

Changes in BA physiology and receptor activities after RYGB and VSG likely support weight loss and promote sustained metabolic improvements.

Keywords

Bariatric surgery Gastric bypass Sleeve gastrectomy Type 2 diabetes Bile acids Farnesoid X receptor 

Notes

Compliance with Ethical Standards

Conflict of Interest

Matthew G. Browning, Bernardo M. Pessoa, Jad Khoraki, and Guilherme M. Campos declare they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Hales CM, et al. Trends in obesity and severe obesity prevalence in US youth and adults by sex and age, 2007-2008 to 2015-2016. JAMA. 2018;319(16):1723–1725.Google Scholar
  2. 2.
    Makinen J, et al. Obesity-associated intestinal insulin resistance is ameliorated after bariatric surgery. Diabetologia. 2015;58(5):1055–62.PubMedCentralGoogle Scholar
  3. 3.
    Boersma GJ, Johansson E, Pereira MJ, Heurling K, Skrtic S, Lau J, et al. Altered glucose uptake in muscle, visceral adipose tissue, and brain predict whole-body insulin resistance and may contribute to the development of type 2 diabetes: a combined PET/MR study. Horm Metab Res. 2018;50(8):627–39.Google Scholar
  4. 4.
    Dadson P, Landini L, Helmiö M, Hannukainen JC, Immonen H, Honka MJ, et al. Effect of bariatric surgery on adipose tissue glucose metabolism in different depots in patients with or without type 2 diabetes. Diabetes Care. 2016;39(2):292–9.Google Scholar
  5. 5.
    Immonen H, Hannukainen JC, Iozzo P, Soinio M, Salminen P, Saunavaara V, et al. Effect of bariatric surgery on liver glucose metabolism in morbidly obese diabetic and non-diabetic patients. J Hepatol. 2014;60(2):377–83.Google Scholar
  6. 6.
    Sung KC, Lee MY, Kim YH, Huh JH, Kim JY, Wild SH, et al. Obesity and incidence of diabetes: effect of absence of metabolic syndrome, insulin resistance, inflammation and fatty liver. Atherosclerosis. 2018;275:50–7.Google Scholar
  7. 7.
    Lazo M, Hernaez R, Eberhardt MS, Bonekamp S, Kamel I, Guallar E, et al. Prevalence of nonalcoholic fatty liver disease in the United States: the Third National Health and Nutrition Examination Survey, 1988-1994. Am J Epidemiol. 2013;178(1):38–45.PubMedCentralGoogle Scholar
  8. 8.
    Bedossa P, et al. Systematic review of bariatric surgery liver biopsies clarifies the natural history of liver disease in patients with severe obesity. Gut. 2016.Google Scholar
  9. 9.
    Bennion LJ, Grundy SM. Effects of diabetes mellitus on cholesterol metabolism in man. N Engl J Med. 1977;296(24):1365–71.Google Scholar
  10. 10.
    Makishima M, Okamoto AY, Repa JJ, Tu H, Learned RM, Luk A, et al. Identification of a nuclear receptor for bile acids. Science. 1999;284(5418):1362–5.Google Scholar
  11. 11.
    Parks DJ, Blanchard SG, Bledsoe RK, Chandra G, Consler TG, Kliewer SA, et al. Bile acids: natural ligands for an orphan nuclear receptor. Science. 1999;284(5418):1365–8.Google Scholar
  12. 12.
    Chavez-Talavera O, et al. Bile acid control of metabolism and inflammation in obesity, type 2 diabetes, dyslipidemia, and nonalcoholic fatty liver disease. Gastroenterology. 2017;152(7):1679–1694.e3.Google Scholar
  13. 13.
    •• Cole AJ, et al. The influence of bariatric surgery on serum bile acids in humans and potential metabolic and hormonal implications: a systematic review. Curr Obes Rep. 2015;4(4):441–50. This is an excellent review summarizing changes in the size and composition of the systemic bile acid pool following different bariatric surgeries. Google Scholar
  14. 14.
    Penney NC, Kinross J, Newton RC, Purkayastha S. The role of bile acids in reducing the metabolic complications of obesity after bariatric surgery: a systematic review. Int J Obes. 2015;39(11):1565–74.Google Scholar
  15. 15.
    Bozadjieva N, Heppner KM, Seeley RJ. Targeting FXR and FGF19 to treat metabolic diseases—lessons learned from bariatric surgery. Diabetes. 2018;67(9):1720–8.Google Scholar
  16. 16.
    English WJ, DeMaria EJ, Brethauer SA, Mattar SG, Rosenthal RJ, Morton JM. American Society for Metabolic and Bariatric Surgery estimation of metabolic and bariatric procedures performed in the United States in 2016. Surg Obes Relat Dis. 2018;14(3):259–63.Google Scholar
  17. 17.
    Risstad H, Kristinsson JA, Fagerland MW, le Roux CW, Birkeland KI, Gulseth HL, 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(9):1544–53.Google Scholar
  18. 18.
    Belgaumkar AP, et al. Changes in bile acid profile after laparoscopic sleeve gastrectomy are associated with improvements in metabolic profile and fatty liver disease. Obes Surg. 2016;26(6):1195–202.Google Scholar
  19. 19.
    Sachdev S, Wang Q, Billington C, Connett J, Ahmed L, Inabnet W, et al. FGF 19 and bile acids increase following Roux-en-Y gastric bypass but not after medical management in patients with type 2 diabetes. Obes Surg. 2016;26(5):957–65.PubMedCentralGoogle Scholar
  20. 20.
    Mazzini GS, et al. Concomitant PPARalpha and FXR activation as a putative mechanism of NASH improvement after gastric bypass surgery: a GEO datasets analysis. J Gastrointest Surg. 2018.Google Scholar
  21. 21.
    Francque S, Verrijken A, Caron S, Prawitt J, Paumelle R, Derudas B, et al. PPARalpha gene expression correlates with severity and histological treatment response in patients with non-alcoholic steatohepatitis. J Hepatol. 2015;63(1):164–73.Google Scholar
  22. 22.
    Browning MG, Campos GM. Bile acid physiology as the potential driver for the sustained metabolic improvements with bariatric surgery. Surg Obes Relat Dis. 2017;13(9):1553–4.Google Scholar
  23. 23.
    Russell DW. The enzymes, regulation, and genetics of bile acid synthesis. Annu Rev Biochem. 2003;72:137–74.Google Scholar
  24. 24.
    Chiang JY. Regulation of bile acid synthesis: pathways, nuclear receptors, and mechanisms. J Hepatol. 2004;40(3):539–51.Google Scholar
  25. 25.
    Galman C, Angelin B, Rudling M. Bile acid synthesis in humans has a rapid diurnal variation that is asynchronous with cholesterol synthesis. Gastroenterology. 2005;129(5):1445–53.Google Scholar
  26. 26.
    Duane WC, Javitt NB. 27-hydroxycholesterol: production rates in normal human subjects. J Lipid Res. 1999;40(7):1194–9.Google Scholar
  27. 27.
    Duane WC, Javitt NB. Conversion of 7 alpha-hydroxycholesterol to bile acid in human subjects: is there an alternate pathway favoring cholic acid synthesis? J Lab Clin Med. 2002;139(2):109–15.Google Scholar
  28. 28.
    Hofmann AF, Hagey LR. Key discoveries in bile acid chemistry and biology and their clinical applications: history of the last eight decades. J Lipid Res. 2014;55(8):1553–95.PubMedCentralGoogle Scholar
  29. 29.
    Heuman DM. Quantitative estimation of the hydrophilic-hydrophobic balance of mixed bile salt solutions. J Lipid Res. 1989;30(5):719–30.Google Scholar
  30. 30.
    Sips FLP, Eggink HM, Hilbers PAJ, Soeters MR, Groen AK, van Riel NAW. In silico analysis identifies intestinal transit as a key determinant of systemic bile acid metabolism. Front Physiol. 2018;9:631.PubMedCentralGoogle Scholar
  31. 31.
    Hylemon PB, Harris SC, Ridlon JM. Metabolism of hydrogen gases and bile acids in the gut microbiome. FEBS Lett. 2018;592(12):2070–82.Google Scholar
  32. 32.
    Liu J, Lu H, Lu YF, Lei X, Cui JY, Ellis E, et al. Potency of individual bile acids to regulate bile acid synthesis and transport genes in primary human hepatocyte cultures. Toxicol Sci. 2014;141(2):538–46.PubMedCentralGoogle Scholar
  33. 33.
    Zhang JH, Nolan JD, Kennie SL, Johnston IM, Dew T, Dixon PH, et al. Potent stimulation of fibroblast growth factor 19 expression in the human ileum by bile acids. Am J Physiol Gastrointest Liver Physiol. 2013;304(10):G940–8.PubMedCentralGoogle Scholar
  34. 34.
    Slijepcevic D, et al. Hepatic uptake of conjugated bile acids is mediated by both sodium taurocholate cotransporting polypeptide and organic anion transporting polypeptides and modulated by intestinal sensing of plasma bile acid levels in mice. Hepatology. 2017;66(5):1631–43.PubMedCentralGoogle Scholar
  35. 35.
    Suga T, et al. Preference of conjugated bile acids over unconjugated bile acids as substrates for OATP1B1 and OATP1B3. PLoS One. 2017;12(1):e0169719.Google Scholar
  36. 36.
    Dawson PA, Lan T, Rao A. Bile acid transporters. J Lipid Res. 2009;50(12):2340–57.PubMedCentralGoogle Scholar
  37. 37.
    van Berge-Henegouwen GP, Hofmann AF. Systemic spill-over of bile acids. Eur J Clin Investig. 1983;13(6):433–7.Google Scholar
  38. 38.
    de Aguiar Vallim TQ, Tarling EJ, Edwards PA. Pleiotropic roles of bile acids in metabolism. Cell Metab. 2013;17(5):657–69.PubMedCentralGoogle Scholar
  39. 39.
    • Haeusler RA, et al. Increased bile acid synthesis and impaired bile acid transport in human obesity. J Clin Endocrinol Metab. 2016;101(5):1935–44. This paper highlights a number of differences in bile acid metabolism, conjugation, and transport between subjects with severe obesity and insulin resistance compared to insulin-sensitive subjects with normal body weight. Google Scholar
  40. 40.
    Jiang C, et al. Intestine-selective farnesoid X receptor inhibition improves obesity-related metabolic dysfunction. Nat Commun. 2015;6:10166.PubMedCentralGoogle Scholar
  41. 41.
    Min HK, Kapoor A, Fuchs M, Mirshahi F, Zhou H, Maher J, et al. Increased hepatic synthesis and dysregulation of cholesterol metabolism is associated with the severity of nonalcoholic fatty liver disease. Cell Metab. 2012;15(5):665–74.PubMedCentralGoogle Scholar
  42. 42.
    Haeusler RA, Astiarraga B, Camastra S, Accili D, Ferrannini E. Human insulin resistance is associated with increased plasma levels of 12α-hydroxylated bile acids. Diabetes. 2013;62(12):4184–91.PubMedCentralGoogle Scholar
  43. 43.
    Patankar JV, Wong CK, Morampudi V, Gibson WT, Vallance B, Ioannou GN, et al. Genetic ablation of Cyp8b1 preserves host metabolic function by repressing steatohepatitis and altering gut microbiota composition. Am J Physiol Endocrinol Metab. 2018;314(5):E418–e432.Google Scholar
  44. 44.
    Bertaggia E, Jensen KK, Castro-Perez J, Xu Y, di Paolo G, Chan RB, et al. Cyp8b1 ablation prevents Western diet-induced weight gain and hepatic steatosis because of impaired fat absorption. Am J Physiol Endocrinol Metab. 2017;313(2):E121–e133.PubMedCentralGoogle Scholar
  45. 45.
    Flynn CR, Albaugh VL, Cai S, Cheung-Flynn J, Williams PE, Brucker RM, et al. Bile diversion to the distal small intestine has comparable metabolic benefits to bariatric surgery. Nat Commun. 2015;6:7715.PubMedCentralGoogle Scholar
  46. 46.
    Verbeek J, Lannoo M, Pirinen E, Ryu D, Spincemaille P, Vander Elst I, et al. Roux-en-Y gastric bypass attenuates hepatic mitochondrial dysfunction in mice with non-alcoholic steatohepatitis. Gut. 2015;64(4):673–83.Google Scholar
  47. 47.
    Pineda Torra I, Claudel T, Duval C, Kosykh V, Fruchart JC, Staels B. Bile acids induce the expression of the human peroxisome proliferator-activated receptor alpha gene via activation of the farnesoid X receptor. Mol Endocrinol. 2003;17(2):259–72.Google Scholar
  48. 48.
    Shen LL, Liu H, peng J, Gan L, Lu L, Zhang Q, et al. Effects of farnesoid X receptor on the expression of the fatty acid synthetase and hepatic lipase. Mol Biol Rep. 2011;38(1):553–9.Google Scholar
  49. 49.
    Savkur RS, Bramlett KS, Michael LF, Burris TP. Regulation of pyruvate dehydrogenase kinase expression by the farnesoid X receptor. Biochem Biophys Res Commun. 2005;329(1):391–6.Google Scholar
  50. 50.
    Cai K, Sewer MB. Diacylglycerol kinase theta couples farnesoid X receptor-dependent bile acid signalling to Akt activation and glucose homoeostasis in hepatocytes. Biochem J. 2013;454(2):267–74.PubMedCentralGoogle Scholar
  51. 51.
    Bhatnagar S, Damron HA, Hillgartner FB. Fibroblast growth factor-19, a novel factor that inhibits hepatic fatty acid synthesis. J Biol Chem. 2009;284(15):10023–33.PubMedCentralGoogle Scholar
  52. 52.
    Escalona A, et al. Bile acids synthesis decreases after laparoscopic sleeve gastrectomy. Surg Obes Relat Dis. 2016;12(4):763–769.Google Scholar
  53. 53.
    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):183–8.PubMedCentralGoogle Scholar
  54. 54.
    Cavin JB, et al. Differences in alimentary glucose absorption and intestinal disposal of blood glucose after Roux-en-Y gastric bypass vs sleeve gastrectomy. Gastroenterology. 2016;150(2):454–64.e9.Google Scholar
  55. 55.
    Magkos F, Bradley D, Eagon JC, Patterson BW, Klein S. Effect of Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding on gastrointestinal metabolism of ingested glucose. Am J Clin Nutr. 2016;103(1):61–5.Google Scholar
  56. 56.
    Deal RA, Tang Y, Fletcher R, Torquati A, Omotosho P. Understanding intestinal glucose transporter expression in obese compared to non-obese subjects. Surg Endosc. 2018;32(4):1755–61.Google Scholar
  57. 57.
    Zhai H, Li Z, Peng M, Huang Z, Qin T, Chen L, et al. Takeda G protein-coupled receptor 5-mechanistic target of rapamycin complex 1 signaling contributes to the increment of glucagon-like peptide-1 production after Roux-en-Y gastric bypass. EBioMedicine. 2018;32:201–14.PubMedCentralGoogle Scholar
  58. 58.
    Harris LLS, et al. Roux-en-Y gastric bypass surgery has unique effects on postprandial FGF21 but not FGF19 secretion. J Clin Endocrinol Metab. 2017;102(10):3858–64.PubMedCentralGoogle Scholar
  59. 59.
    Jorgensen NB, et al. Improvements in glucose metabolism early after gastric bypass surgery are not explained by increases in total bile acids and fibroblast growth factor 19 concentrations. J Clin Endocrinol Metab. 2015;100(3):E396–406.Google Scholar
  60. 60.
    Li P, Zhu L, Yang X, Li W, Sun X, Yi B, et al. Farnesoid X receptor interacts with cAMP response element binding protein to modulate glucagon-like peptide-1 (7-36) amide secretion by intestinal L cell. J Cell Physiol. 2018.Google Scholar
  61. 61.
    Trabelsi MS, Daoudi M, Prawitt J, Ducastel S, Touche V, Sayin SI, et al. Farnesoid X receptor inhibits glucagon-like peptide-1 production by enteroendocrine L cells. Nat Commun. 2015;6:7629.PubMedCentralGoogle Scholar
  62. 62.
    Bernsmeier C, Meyer-Gerspach AC, Blaser LS, Jeker L, Steinert RE, Heim MH, et al. Glucose-induced glucagon-like peptide 1 secretion is deficient in patients with non-alcoholic fatty liver disease. PLoS One. 2014;9(1):e87488.PubMedCentralGoogle Scholar
  63. 63.
    Vilsboll T, Krarup T, Deacon CF, Madsbad S, Holst JJ. Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes. 2001;50(3):609–13.Google Scholar
  64. 64.
    Xu B, Yan X, Shao Y, Shen Q, Hua R, Ding R, et al. A comparative study of the effect of gastric bypass, sleeve gastrectomy, and duodenal-jejunal bypass on type-2 diabetes in non-obese rats. Obes Surg. 2015;25(10):1966–75.Google Scholar
  65. 65.
    Peterli R, Wölnerhanssen B, Peters T, Devaux N, Kern B, Christoffel-Courtin C, et al. Improvement in glucose metabolism after bariatric surgery: comparison of laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy: a prospective randomized trial. Ann Surg. 2009;250(2):234–41.Google Scholar
  66. 66.
    Mokadem M, Zechner JF, Margolskee RF, Drucker DJ, Aguirre V. 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.Google Scholar
  67. 67.
    Pardina E, Ferrer R, Rossell J, Baena-Fustegueras JA, Lecube A, Fort JM, et al. Diabetic and dyslipidaemic morbidly obese exhibit more liver alterations compared with healthy morbidly obese. BBA Clin. 2016;5:54–65.PubMedCentralGoogle Scholar
  68. 68.
    Simonen M, Dali-Youcef N, Kaminska D, Venesmaa S, Käkelä P, Pääkkönen M, 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.PubMedCentralGoogle Scholar
  69. 69.
    Myronovych A, Kirby M, Ryan KK, Zhang W, Jha P, Setchell KDR, et al. Vertical sleeve gastrectomy reduces hepatic steatosis while increasing serum bile acids in a weight-loss-independent manner. Obesity (Silver Spring). 2014;22(2):390–400.Google Scholar
  70. 70.
    Wu Q, Zhang X, Zhong M, Han H, Liu S, Liu T, et al. Effects of bariatric surgery on serum bile acid composition and conjugation in a diabetic rat model. Obes Surg. 2016;26(10):2384–92.Google Scholar
  71. 71.
    Ferrannini E, Camastra S, Astiarraga B, Nannipieri M, Castro-Perez J, Xie D, et al. Increased bile acid synthesis and deconjugation after biliopancreatic diversion. Diabetes. 2015;64(10):3377–85.PubMedCentralGoogle Scholar
  72. 72.
    de Siqueira Cardinelli C, et al. Fecal bile acid profile after Roux-en-Y gastric bypass and its association with the remission of type 2 diabetes in obese women: a preliminary study. Clin Nutr. 2019; [in press].Google Scholar
  73. 73.
    Duran-Sandoval D, Mautino G, Martin G, Percevault F, Barbier O, Fruchart JC, et al. Glucose regulates the expression of the farnesoid X receptor in liver. Diabetes. 2004;53(4):890–8.Google Scholar
  74. 74.
    Berrabah W, Aumercier P, Gheeraert C, Dehondt H, Bouchaert E, Alexandre J, et al. Glucose sensing O-GlcNAcylation pathway regulates the nuclear bile acid receptor farnesoid X receptor (FXR). Hepatology. 2014;59(5):2022–33.Google Scholar
  75. 75.
    Yang ZX, Shen W, Sun H. Effects of nuclear receptor FXR on the regulation of liver lipid metabolism in patients with non-alcoholic fatty liver disease. Hepatol Int. 2010;4(4):741–8.PubMedCentralGoogle Scholar
  76. 76.
    Yao J, Zhou CS, Ma X, Fu BQ, Tao LS, Chen M, et al. FXR agonist GW4064 alleviates endotoxin-induced hepatic inflammation by repressing macrophage activation. World J Gastroenterol. 2014;20(39):14430–41.PubMedCentralGoogle Scholar
  77. 77.
    Gerhard GS, Styer AM, Wood GC, Roesch SL, Petrick AT, Gabrielsen J, 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.PubMedCentralGoogle Scholar
  78. 78.
    • Roesch SL, et al. Perturbations of fibroblast growth factors 19 and 21 in type 2 diabetes. PLoS One. 2015;10(2):e0116928. This paper details associations between bile acid synthesis and signaling with type 2 diabetes remission after gastric bypass surgery. PubMedCentralGoogle Scholar
  79. 79.
    Jahansouz C, Xu H, Hertzel AV, Serrot FJ, Kvalheim N, Cole A, et al. Bile acids increase independently from hypocaloric restriction after bariatric surgery. Ann Surg. 2016;264(6):1022–8.Google Scholar
  80. 80.
    Ullmer C, Alvarez Sanchez R, Sprecher U, Raab S, Mattei P, Dehmlow H, et al. Systemic bile acid sensing by G protein-coupled bile acid receptor 1 (GPBAR1) promotes PYY and GLP-1 release. Br J Pharmacol. 2013;169(3):671–84.PubMedCentralGoogle Scholar
  81. 81.
    • Chavez-Talavera O, et al. Roux-en-Y gastric bypass increases systemic but not portal bile acid concentrations by decreasing hepatic bile acid uptake in minipigs. Int J Obes (Lond). 2017;41(4):664–8. This paper discusses possible mechanisms behind elevated systemic bile acid concentrations after gastric bypass surgery. Google Scholar
  82. 82.
    Laferrere B, Pattou F. Weight-independent mechanisms of glucose control after Roux-en-Y gastric bypass. Front Endocrinol (Lausanne). 2018;9:530.Google Scholar
  83. 83.
    Mahawar KK, Sharples AJ. Contribution of malabsorption to weight loss after Roux-en-Y gastric bypass: a systematic review. Obes Surg. 2017;27(8):2194–206.Google Scholar
  84. 84.
    Watanabe M, Houten SM, Mataki C, Christoffolete MA, Kim BW, Sato H, et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature. 2006;439(7075):484–9.Google Scholar
  85. 85.
    Broeders EP, et al. The bile acid chenodeoxycholic acid increases human brown adipose tissue activity. Cell Metab. 2015;22(3):418–26.Google Scholar
  86. 86.
    Kars M, Yang L, Gregor MF, Mohammed BS, Pietka TA, Finck BN, et al. Tauroursodeoxycholic acid may improve liver and muscle but not adipose tissue insulin sensitivity in obese men and women. Diabetes. 2010;59(8):1899–905.PubMedCentralGoogle Scholar
  87. 87.
    Worthmann A, John C, Ruhlemann MC. Cold-induced conversion of cholesterol to bile acids in mice shapes the gut microbiome and promotes adaptive thermogenesis. Nat Med. 2017;23(7):839–49.Google Scholar
  88. 88.
    Rachid B, et al. Distinct regulation of hypothalamic and brown/beige adipose tissue activities in human obesity. Int J Obes (Lond). 2015;39(10):1515–22.Google Scholar
  89. 89.
    Vijgen GH, et al. Increase in brown adipose tissue activity after weight loss in morbidly obese subjects. J Clin Endocrinol Metab. 2012;97(7):E1229–33.Google Scholar
  90. 90.
    Svensson PA, Olsson M, Andersson-Assarsson JC, Taube M, Pereira MJ, Froguel P, et al. The TGR5 gene is expressed in human subcutaneous adipose tissue and is associated with obesity, weight loss and resting metabolic rate. Biochem Biophys Res Commun. 2013;433(4):563–6.PubMedCentralGoogle Scholar
  91. 91.
    La Frano MR, et al. Diet-induced obesity and weight loss alter bile acid concentrations and bile acid-sensitive gene expression in insulin target tissues of C57BL/6J mice. Nutr Res. 2017;46:11–21.Google Scholar
  92. 92.
    Teodoro JS, Rolo AP, Jarak I, Palmeira CM, Carvalho RA. The bile acid chenodeoxycholic acid directly modulates metabolic pathways in white adipose tissue in vitro: insight into how bile acids decrease obesity. NMR Biomed. 2016;29(10):1391–402.Google Scholar
  93. 93.
    Pourhassan M, Glüer CC, Pick P, Tigges W, Müller MJ. Impact of weight loss-associated changes in detailed body composition as assessed by whole-body MRI on plasma insulin levels and homeostatis model assessment index. Eur J Clin Nutr. 2017;71(2):212–8.Google Scholar
  94. 94.
    Fothergill E, et al. Persistent metabolic adaptation 6 years after “The Biggest Loser” competition. Obesity (Silver Spring). 2016;24(8):1612–9.Google Scholar
  95. 95.
    Schauer PR, Bhatt DL, Kirwan JP, Wolski K, Aminian A, Brethauer SA, et al. Bariatric surgery versus intensive medical therapy for diabetes—5-year outcomes. N Engl J Med. 2017;376(7):641–51.PubMedCentralGoogle Scholar
  96. 96.
    Shouhed D, Steggerda J, Burch M, Noureddin M. The role of bariatric surgery in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Expert Rev Gastroenterol Hepatol. 2017;11(9):797–811.Google Scholar
  97. 97.
    Thoni V, et al. Dynamics of bile acid profiles, GLP-1, and FGF19 after laparoscopic gastric banding. J Clin Endocrinol Metab. 2017;102(8):2974–84.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Matthew G. Browning
    • 1
  • Bernardo M. Pessoa
    • 1
  • Jad Khoraki
    • 1
  • Guilherme M. Campos
    • 1
    Email author
  1. 1.Division of Bariatric and Gastrointestinal Surgery, Department of Surgery, Medical College of VirginiaVirginia Commonwealth University School of MedicineRichmondUSA

Personalised recommendations