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Targeting Bile Acid-Activated Receptors in Bariatric Surgery

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Bile Acids and Their Receptors

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 256))

Abstract

Bariatric surgical procedures, including Roux-en-Y gastric bypass and vertical sleeve gastrectomy, are currently the most effective clinical approaches to achieve a significant and sustainable weight loss. Bariatric surgery also concomitantly improves type 2 diabetes and other metabolic diseases such as nonalcoholic steatohepatitis, cardiovascular diseases, and hyperlipidemia. However, despite the recent exciting progress in the understanding how bariatric surgery works, the underlying molecular mechanisms of bariatric surgery remain largely unknown. Interestingly, bile acids are emerging as potential signaling molecules to mediate the beneficial effects of bariatric surgery. In this review, we summarize the recent findings on bile acids and their activated receptors in mediating the beneficial metabolic effects of bariatric surgery. We also discuss the potential to target bile acid-activated receptors in order to treat obesity and other metabolic diseases.

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Abbreviations

BA:

Bile acid

FXR:

Farnesoid X receptor

NAFLD:

Nonalcoholic fatty liver disease

NASH:

Nonalcoholic steatohepatitis

RYGB:

Roux-en-Y gastric bypass

T2D:

Type 2 diabetes

TGR5:

G protein-coupled bile acid receptor 1 (GPBAR-1, MBAR1, or TGR5)

VSG:

Vertical sleeve gastrectomy

References

  • Abdelaal M, le Roux CW, Docherty NG (2017) Morbidity and mortality associated with obesity. Ann Transl Med 5(7):161

    Article  PubMed  PubMed Central  Google Scholar 

  • Ahmad NN, Pfalzer A, Kaplan LM (2013) Roux-en-Y gastric bypass normalizes the blunted postprandial bile acid excursion associated with obesity. Int J Obes (Lond) 37(12):1553–1559

    Article  CAS  Google Scholar 

  • Akinrotimi O et al (2017) Small heterodimer partner deletion prevents hepatic steatosis and when combined with farnesoid X receptor loss protects against type 2 diabetes in mice. Hepatology 66(6):1854–1865

    Article  CAS  PubMed  Google Scholar 

  • Albaugh VL et al (2015) Early increases in bile acids post Roux-en-Y gastric bypass are driven by insulin-sensitizing, secondary bile acids. J Clin Endocrinol Metabol 100(9):E1225–E1233

    Article  Google Scholar 

  • Albaugh VL et al (2017) Bile acids and bariatric surgery. Mol Aspects Med 56:75–89

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ali AH, Carey EJ, Lindor KD (2015) Recent advances in the development of farnesoid X receptor agonists. Ann Transl Med 3(1):5

    PubMed  PubMed Central  Google Scholar 

  • Anhe FF et al (2017) The gut microbiota as a mediator of metabolic benefits after bariatric surgery. Can J Diabetes 41(4):439–447

    Article  PubMed  Google Scholar 

  • Anker SD, Anker MS, von Haehling S (2016) Weight loss and health status after bariatric surgery in adolescents. N Engl J Med 374(20):1988

    Article  PubMed  Google Scholar 

  • Arble DM, Sandoval DA, Seeley RJ (2015a) Mechanisms underlying weight loss and metabolic improvements in rodent models of bariatric surgery. Diabetologia 58(2):211–220

    Article  CAS  PubMed  Google Scholar 

  • Arble DM et al (2015b) Metabolic effects of bariatric surgery in mouse models of circadian disruption. Int J Obes (Lond) 39(8):1310–1318

    Article  CAS  Google Scholar 

  • Arble DM et al (2018) Metabolic comparison of one-anastomosis gastric bypass, single-anastomosis duodenal-switch, Roux-en-Y gastric bypass, and vertical sleeve gastrectomy in rat. Surg Obes Relat Dis 14(12):1857–1867

    Article  PubMed  PubMed Central  Google Scholar 

  • Arterburn DE, Courcoulas AP (2014) Bariatric surgery for obesity and metabolic conditions in adults. BMJ 349:g3961

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bauer PV et al (2018) Metformin alters upper small intestinal microbiota that impact a glucose-SGLT1-sensing glucoregulatory pathway. Cell Metab 27(1):101–117

    Article  CAS  PubMed  Google Scholar 

  • Bayham BE et al (2012) Early resolution of type 2 diabetes seen after Roux-en-Y gastric bypass and vertical sleeve gastrectomy. Diabetes Technol Ther 14(1):30–34

    Article  PubMed  Google Scholar 

  • Bechmann LP et al (2013) 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(4):1394–1406

    Article  CAS  PubMed  Google Scholar 

  • Belgaumkar AP et al (2016) Changes in bile acid profile after laparoscopic sleeve gastrectomy are associated with improvements in metabolic profile and fatty liver disease. Obes Surg 26(6):1195–1202

    Article  PubMed  Google Scholar 

  • Benaiges D et al (2011) Laparoscopic sleeve gastrectomy and laparoscopic gastric bypass are equally effective for reduction of cardiovascular risk in severely obese patients at one year of follow-up. Surg Obes Relat Dis 7(5):575–580

    Article  PubMed  Google Scholar 

  • Benaiges D et al (2012) Impact of restrictive (sleeve gastrectomy) vs hybrid bariatric surgery (Roux-en-Y gastric bypass) on lipid profile. Obes Surg 22(8):1268–1275

    Article  CAS  PubMed  Google Scholar 

  • Benotti P et al (2014) Risk factors associated with mortality after Roux-en-Y gastric bypass surgery. Ann Surg 259(1):123–130

    Article  PubMed  Google Scholar 

  • Bhutta HY et al (2015) Effect of Roux-en-Y gastric bypass surgery on bile acid metabolism in normal and obese diabetic rats. PLoS One 10(3):e0122273

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Blanchard C et al (2018) Roux-en-Y gastric bypass reduces plasma cholesterol in diet-induced obese mice by affecting trans-intestinal cholesterol excretion and intestinal cholesterol absorption. Int J Obes (Lond) 42(3):552–560

    Article  CAS  Google Scholar 

  • Breen DM et al (2013) Nutrient-sensing mechanisms in the gut as therapeutic targets for diabetes. Diabetes 62(9):3005–3013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brighton CA et al (2015) Bile acids trigger GLP-1 release predominantly by accessing basolaterally located G protein-coupled bile acid receptors. Endocrinology 156(11):3961–3970

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brolin RE et al (1994) Weight loss and dietary intake after vertical banded gastroplasty and Roux-en-Y gastric bypass. Ann Surg 220(6):782–790

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Buffie CG et al (2015) Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature 517(7533):205–208

    Article  CAS  PubMed  Google Scholar 

  • Cazzo E et al (2014) Impact of Roux-en-Y gastric bypass on metabolic syndrome and insulin resistance parameters. Diabetes Technol Ther 16(4):262–265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chambers AP et al (2011) Weight-independent changes in blood glucose homeostasis after gastric bypass or vertical sleeve gastrectomy in rats. Gastroenterology 141(3):950–958

    Article  CAS  PubMed  Google Scholar 

  • Chambers AP et al (2012) Effect of vertical sleeve gastrectomy on food selection and satiation in rats. Am J Physiol Endocrinol Metab 303(8):E1076–E1084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chiang JY (1998) Regulation of bile acid synthesis. Front Biosci 3:d176–d193

    Article  CAS  PubMed  Google Scholar 

  • Cummings DE, Overduin J, Foster-Schubert KE (2004) Gastric bypass for obesity: mechanisms of weight loss and diabetes resolution. J Clin Endocrinol Metab 89(6):2608–2615

    Article  CAS  PubMed  Google Scholar 

  • Cummings BP et al (2012) Vertical sleeve gastrectomy improves glucose and lipid metabolism and delays diabetes onset in UCD-T2DM rats. Endocrinology 153(8):3620–3632

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Davidson WS et al (2017) Weight loss surgery in adolescents corrects high-density lipoprotein subspecies and their function. Int J Obes (Lond) 41(1):83–89

    Article  CAS  Google Scholar 

  • de Boer JF et al (2017) Intestinal farnesoid X receptor controls transintestinal cholesterol excretion in mice. Gastroenterology 152(5):1126–1138

    Article  PubMed  CAS  Google Scholar 

  • De Giorgi S et al (2015) Long-term effects of Roux-en-Y gastric bypass on postprandial plasma lipid and bile acids kinetics in female non diabetic subjects: A cross-sectional pilot study. Clin Nutr 34(5):911–917

    Article  PubMed  CAS  Google Scholar 

  • Ding L et al (2016) Vertical sleeve gastrectomy activates GPBAR-1/TGR5 to sustain weight loss, improve fatty liver, and remit insulin resistance in mice. Hepatology 64(3):760–773

    Article  CAS  PubMed  Google Scholar 

  • Dirksen C et al (2013) Fast pouch emptying, delayed small intestinal transit, and exaggerated gut hormone responses after Roux-en-Y gastric bypass. Neurogastroenterol Motil 25(4):346–e255

    Article  CAS  PubMed  Google Scholar 

  • Donepudi AC et al (2017) G-protein-coupled bile acid receptor plays a key role in bile acid metabolism and fasting-induced hepatic steatosis in mice. Hepatology 65(3):813–827

    Article  CAS  PubMed  Google Scholar 

  • Douros JD et al (2018) Enhanced glucose control following vertical sleeve gastrectomy does not require a beta-cell glucagon-like peptide 1 receptor. Diabetes 67(8):1504–1511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Du J et al (2017) Vertical sleeve gastrectomy reverses diet-induced gene-regulatory changes impacting lipid metabolism. Sci Rep 7(1):5274

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Duboc H, Tache Y, Hofmann AF (2014) The bile acid TGR5 membrane receptor: from basic research to clinical application. Dig Liver Dis 46(4):302–312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fan M et al (2015) Bile acid signaling and liver regeneration. Biochim Biophys Acta 1849(2):196–200

    Article  CAS  PubMed  Google Scholar 

  • Finn PD et al (2019) Intestinal TGR5 agonism improves hepatic steatosis and insulin sensitivity in Western diet-fed mice. Am J Physiol Gastrointest Liver Physiol 316(3):G412–G424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fiorucci S et al (2009) Bile-acid-activated receptors: targeting TGR5 and farnesoid-X-receptor in lipid and glucose disorders. Trends Pharmacol Sci 30(11):570–580

    Article  CAS  PubMed  Google Scholar 

  • Flynn CR et al (2015) Bile diversion to the distal small intestine has comparable metabolic benefits to bariatric surgery. Nat Commun 6:7715

    Article  CAS  PubMed  Google Scholar 

  • Friedman SL et al (2018) Mechanisms of NAFLD development and therapeutic strategies. Nat Med 24(7):908–922

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gerhard GS et al (2013) A role for fibroblast growth factor 19 and bile acids in diabetes remission after Roux-en-Y gastric bypass. Diabetes Care 36(7):1859–1864

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gonzalez FJ, Jiang C, Patterson AD (2016) An intestinal microbiota-farnesoid X receptor axis modulates metabolic disease. Gastroenterology 151(5):845–859

    Article  CAS  PubMed  Google Scholar 

  • Grayson BE et al (2014) Improvements in hippocampal-dependent memory and microglial infiltration with calorie restriction and gastric bypass surgery, but not with vertical sleeve gastrectomy. Int J Obes (Lond) 38(3):349–356

    Article  CAS  Google Scholar 

  • Gregg EW, Shaw JE (2017) Global health effects of overweight and obesity. N Engl J Med 377(1):80–81

    Article  PubMed  Google Scholar 

  • Hady HR et al (2012) The influence of laparoscopic adjustable gastric banding and laparoscopic sleeve gastrectomy on weight loss, plasma ghrelin, insulin, glucose and lipids. Folia Histochem Cytobiol 50(2):292–303

    Article  CAS  PubMed  Google Scholar 

  • Haeusler RA et al (2013) Human insulin resistance is associated with increased plasma levels of 12a-hydroxylated bile acids. Diabetes 62(12):4184–4191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haluzikova D et al (2013) Laparoscopic sleeve gastrectomy differentially affects serum concentrations of FGF-19 and FGF-21 in morbidly obese subjects. Obesity (Silver Spring) 21(7):1335–1342

    Article  CAS  Google Scholar 

  • Hao Z et al (2018) Roux-en-Y gastric bypass surgery-induced weight loss and metabolic improvements are similar in TGR5-deficient and wildtype mice. Obes Surg 28(10):3227–3236

    Article  PubMed  PubMed Central  Google Scholar 

  • Higuchi A, Kami M (2017) Obesity management in primary care. Lancet 389(10079):1606

    Article  PubMed  Google Scholar 

  • Hutch CR, Sandoval D (2017) The role of GLP-1 in the metabolic success of bariatric surgery. Endocrinology 158(12):4139–4151

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jahansouz C et al (2016) Bile acids increase independently from hypocaloric restriction after bariatric surgery. Ann Surg 264(6):1022–1028

    Article  PubMed  Google Scholar 

  • Jahansouz C et al (2018) Antibiotic-induced disruption of intestinal microbiota contributes to failure of vertical sleeve gastrectomy. Ann Surg. https://doi.org/10.1097/SLA.0000000000002729

    Article  PubMed  Google Scholar 

  • Jiang C et al (2015) Intestine-selective farnesoid X receptor inhibition improves obesity-related metabolic dysfunction. Nat Commun 6:10166

    Article  CAS  PubMed  Google Scholar 

  • Jiao N et al (2018) Suppressed hepatic bile acid signalling despite elevated production of primary and secondary bile acids in NAFLD. Gut 67(10):1881–1891

    Article  CAS  PubMed  Google Scholar 

  • Jorgensen NB et al (2012) Acute and long-term effects of Roux-en-Y gastric bypass on glucose metabolism in subjects with type 2 diabetes and normal glucose tolerance. Am J Physiol Endocrinol Metab 303(1):E122–E131

    Article  CAS  PubMed  Google Scholar 

  • Jorgensen NB et al (2015) 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 100(3):E396–E406

    Article  CAS  PubMed  Google Scholar 

  • Kalinowski P et al (2017) Ghrelin, leptin, and glycemic control after sleeve gastrectomy versus Roux-en-Y gastric bypass-results of a randomized clinical trial. Surg Obes Relat Dis 13(2):181–188

    Article  PubMed  Google Scholar 

  • Kaska L et al (2016) Improved glucose metabolism following bariatric surgery is associated with increased circulating bile acid concentrations and remodeling of the gut microbiome. World J Gastroenterol 22(39):8698–8719

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Katsuma S, Hirasawa A, Tsujimoto G (2005) Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1. Biochem Biophys Res Commun 329(1):386–390

    Article  CAS  PubMed  Google Scholar 

  • Keitel V, Haussinger D (2012) Perspective: TGR5 (Gpbar-1) in liver physiology and disease. Clin Res Hepatol Gastroenterol 36(5):412–419

    Article  CAS  PubMed  Google Scholar 

  • Kohli R et al (2013a) Weight loss induced by Roux-en-Y gastric bypass but not laparoscopic adjustable gastric banding increases circulating bile acids. J Clin Endocrinol Metab 98(4):E708–E712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kohli R et al (2013b) A surgical model in male obese rats uncovers protective effects of bile acids post-bariatric surgery. Endocrinology 154(7):2341–2351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kohli R et al (2015) Bile acid signaling: mechanism for bariatric surgery, cure for NASH? Dig Dis 33(3):440–446

    Article  PubMed  Google Scholar 

  • Kuhre RE, Holst JJ, Kappe C (2016) The regulation of function, growth and survival of GLP-1-producing L-cells. Clin Sci (Lond) 130(2):79–91

    Article  CAS  Google Scholar 

  • Kuipers F, Bloks VW, Groen AK (2014) Beyond intestinal soap – bile acids in metabolic control. Nat Rev Endocrinol 10(8):488–498

    Article  CAS  PubMed  Google Scholar 

  • Kumar DP et al (2016) Activation of transmembrane bile acid receptor TGR5 modulates pancreatic islet alpha cells to promote glucose homeostasis. J Biol Chem 291(13):6626–6640

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lamers C, Schubert-Zsilavecz M, Merk D (2014) Medicinal chemistry and pharmacological effects of Farnesoid X Receptor (FXR) antagonists. Curr Top Med Chem 14(19):2188–2205

    Article  CAS  PubMed  Google Scholar 

  • Lassailly G et al (2015) Bariatric surgery reduces features of nonalcoholic steatohepatitis in morbidly obese patients. Gastroenterology 149(2):379–388. quiz e315–376

    Article  PubMed  Google Scholar 

  • le Roux CW et al (2011) Gastric bypass reduces fat intake and preference. Am J Physiol Regul Integr Comp Physiol 301(4):R1057–R1066

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li T, Chiang JY (2014) Bile acid signaling in metabolic disease and drug therapy. Pharmacol Rev 66(4):948–983

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li T, Chiang JY (2015) Bile acids as metabolic regulators. Curr Opin Gastroenterol 31(2):159–165

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li JV et al (2011) Metabolic surgery profoundly influences gut microbial-host metabolic cross-talk. Gut 60(9):1214–1223

    Article  CAS  PubMed  Google Scholar 

  • Li Y, Jadhav K, Zhang Y (2013) Bile acid receptors in non-alcoholic fatty liver disease. Biochem Pharmacol 86(11):1517–1524

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li S et al (2014) Cytoplasmic tyrosine phosphatase Shp2 coordinates hepatic regulation of bile acid and FGF15/19 signaling to repress bile acid synthesis. Cell Metab 20(2):320–332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liou AP et al (2013) Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci Transl Med 5(178):178ra141

    Article  CAS  Google Scholar 

  • Liu W et al (2008) Establishment of duodenojejunal bypass surgery in mice: a model designed for diabetic research. Microsurgery 28(3):197–202

    Article  PubMed  Google Scholar 

  • Liu H et al (2016) Cholesterol 7alpha-hydroxylase protects the liver from inflammation and fibrosis by maintaining cholesterol homeostasis. J Lipid Res 57(10):1831–1844

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu R et al (2017) Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention. Nat Med 23(7):859–868

    Article  CAS  PubMed  Google Scholar 

  • McGavigan AK et al (2017) TGR5 contributes to glucoregulatory improvements after vertical sleeve gastrectomy in mice. Gut 66(2):226–234

    Article  CAS  PubMed  Google Scholar 

  • Mokadem M et al (2015) Leptin is required for glucose homeostasis and weight maintenance after Roux-en-Y gastric bypass in mice. Gastroenterology 148(4):S11

    Article  Google Scholar 

  • Monte MJ et al (2009) Bile acids: chemistry, physiology, and pathophysiology. World J Gastroenterol 15(7):804–816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mueller M et al (2015) Ursodeoxycholic acid exerts farnesoid X receptor-antagonistic effects on bile acid and lipid metabolism in morbid obesity. J Hepatol 62(6):1398–1404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murphy R et al (2018) Increased bile acids and FGF-19 after sleeve gastrectomy and Roux-en-Y gastric bypass correlate with improvement in type 2 diabetes in a randomized trial. Diabetes 67(Suppl 1). https://doi.org/10.2337/db18-2075-P

    Article  Google Scholar 

  • Myronovych A et al (2014a) The role of small heterodimer partner in nonalcoholic fatty liver disease improvement after sleeve gastrectomy in mice. Obesity (Silver Spring) 22(11):2301–2311

    Article  CAS  Google Scholar 

  • Myronovych A et al (2014b) Vertical sleeve gastrectomy reduces hepatic steatosis while increasing serum bile acids in a weight-loss-independent manner. Obesity 22(2):390–400

    Article  CAS  PubMed  Google Scholar 

  • Nakatani H et al (2009) Serum bile acid along with plasma incretins and serum high-molecular weight adiponectin levels are increased after bariatric surgery. Metabolism 58(10):1400–1407

    Article  CAS  PubMed  Google Scholar 

  • Nannipieri M et al (2013) Roux-en-Y gastric bypass and sleeve gastrectomy: mechanisms of diabetes remission and role of gut hormones. J Clin Endocrinol Metab 98(11):4391–4399

    Article  CAS  PubMed  Google Scholar 

  • Nemati R et al (2018) Increased bile acids and FGF19 after sleeve gastrectomy and Roux-en-Y gastric bypass correlate with improvement in type 2 diabetes in a randomized trial. Obes Surg 28(9):2672–2686

    Article  PubMed  Google Scholar 

  • Noel OF et al (2016) Bile acids, FXR, and metabolic effects of bariatric surgery. J Obes 2016:4390254

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nosso G et al (2016) Comparative effects of Roux-en-Y gastric bypass and sleeve gastrectomy on glucose homeostasis and incretin hormones in obese type 2 diabetic patients: a one-year prospective study. Horm Metab Res 48(5):312–317

    Article  CAS  PubMed  Google Scholar 

  • Nuche-Berenguer B et al (2010) Presence of a functional receptor for GLP-1 in osteoblastic cells, independent of the cAMP-linked GLP-1 receptor. J Cell Physiol 225(2):585–592

    Article  CAS  PubMed  Google Scholar 

  • Parks DJ et al (1999) Bile acids: natural ligands for an orphan nuclear receptor. Science 284(5418):1365–1368

    Article  CAS  PubMed  Google Scholar 

  • Patel A et al (2018) GLP-2 receptor signaling controls circulating bile acid levels but not glucose homeostasis in Gcgr(-/-) mice and is dispensable for the metabolic benefits ensuing after vertical sleeve gastrectomy. Mol Metab 16:45–54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patti ME et al (2009) Serum bile acids are higher in humans with prior gastric bypass: potential contribution to improved glucose and lipid metabolism. Obesity (Silver Spring) 17(9):1671–1677

    Article  CAS  Google Scholar 

  • Perkins WJ et al (2014) Differential effects of laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass on dietary fatty acid absorption, bile acid absorption, and post-prandial gut hormone secretion. Gastroenterology 146(5):S726–S727

    Article  Google Scholar 

  • Puzziferri N et al (2014) Long-term follow-up after bariatric surgery: a systematic review. JAMA 312(9):934–942

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rhee NA et al (2015) Effect of Roux-en-Y gastric bypass on the distribution and hormone expression of small-intestinal enteroendocrine cells in obese patients with type 2 diabetes. Diabetologia 58(10):2254–2258

    Article  CAS  PubMed  Google Scholar 

  • Romero F et al (2012) Comparable early changes in gastrointestinal hormones after sleeve gastrectomy and Roux-En-Y gastric bypass surgery for morbidly obese type 2 diabetic subjects. Surg Endosc 26(8):2231–2239

    Article  PubMed  Google Scholar 

  • Roslin MS et al (2012) Comparison between RYGB, DS, and VSG effect on glucose homeostasis. Obes Surg 22(8):1281–1286

    Article  PubMed  Google Scholar 

  • Rubino F et al (2010) Metabolic surgery to treat type 2 diabetes: clinical outcomes and mechanisms of action. Annu Rev Med 61:393–411

    Article  CAS  PubMed  Google Scholar 

  • Rubino F et al (2016) Metabolic surgery in the treatment algorithm for type 2 diabetes: a joint statement by international diabetes organizations. Diabetes Care 39(6):861–877

    Article  CAS  PubMed  Google Scholar 

  • Ryan KK et al (2014) FXR is a molecular target for the effects of vertical sleeve gastrectomy. Nature 509(7499):183–188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sachdev S et al (2016) 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 26(5):957–965

    Article  PubMed  PubMed Central  Google Scholar 

  • Salinari S et al (2013) Insulin sensitivity and secretion changes after gastric bypass in normotolerant and diabetic obese subjects. Ann Surg 257(3):462–468

    Article  PubMed  Google Scholar 

  • Santiago-Fernandez C et al (2017) Ghrelin levels could be involved in the improvement of insulin resistance after bariatric surgery. Endocrinol Diabetes Nutr 64(7):355–362

    Article  PubMed  Google Scholar 

  • Sayin SI et al (2013) Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab 17(2):225–235

    Article  CAS  PubMed  Google Scholar 

  • Schaap FG, Trauner M, Jansen PL (2014) Bile acid receptors as targets for drug development. Nat Rev Gastroenterol Hepatol 11(1):55–67

    Article  CAS  PubMed  Google Scholar 

  • Schauer PR et al (2017) Bariatric surgery versus intensive medical therapy for diabetes – 5-year outcomes. N Engl J Med 376(7):641–651

    Article  PubMed  PubMed Central  Google Scholar 

  • Simonen M et al (2012) Conjugated bile acids associate with altered rates of glucose and lipid oxidation after Roux-en-Y gastric bypass. Obes Surg 22(9):1473–1480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Spinelli V et al (2016) Influence of Roux-en-Y gastric bypass on plasma bile acid profiles: a comparative study between rats, pigs and humans. Int J Obes (Lond) 40(8):1260–1267

    Article  CAS  Google Scholar 

  • Staels B, Fonseca VA (2009) Bile acids and metabolic regulation: mechanisms and clinical responses to bile acid sequestration. Diabetes Care 32(Suppl 2):S237–S245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stefater MA et al (2010) Sleeve gastrectomy induces loss of weight and fat mass in obese rats, but does not affect leptin sensitivity. Gastroenterology 138(7):2426–2436. 2436.e1-3

    Article  CAS  PubMed  Google Scholar 

  • Stefater MA et al (2011) Sleeve gastrectomy in rats improves postprandial lipid clearance by reducing intestinal triglyceride secretion. Gastroenterology 141(3):939–U675

    Article  CAS  PubMed  Google Scholar 

  • Stefater MA et al (2012) All bariatric surgeries are not created equal: insights from mechanistic comparisons. Endocr Rev 33(4):595–622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stylopoulos N, Hoppin AG, Kaplan LM (2009) Roux-en-Y gastric bypass enhances energy expenditure and extends lifespan in diet-induced obese rats. Obesity 17(10):1839–1847

    Article  PubMed  Google Scholar 

  • Sun L et al (2018) Gut microbiota and intestinal FXR mediate the clinical benefits of metformin. Nat Med 24(12):1919–1929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sweeney TE, Morton JM (2013) The human gut microbiome: a review of the effect of obesity and surgically induced weight loss. JAMA Surg 148(6):563–569

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takahashi S et al (2016) Cyp2c70 is responsible for the species difference in bile acid metabolism between mice and humans. J Lipid Res 57(12):2130–2137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thomas C et al (2009) TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab 10(3):167–177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tomas E, Habener JF (2010) Insulin-like actions of glucagon-like peptide-1: a dual receptor hypothesis. Trends Endocrinol Metab 21(2):59–67

    Article  CAS  PubMed  Google Scholar 

  • Tremaroli V et al (2015) 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(2):228–238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Urizar NL et al (2002) A natural product that lowers cholesterol as an antagonist ligand for FXR. Science 296(5573):1703–1706

    Article  CAS  PubMed  Google Scholar 

  • van Berge-Henegouwen GP, Hofmann AF (1983) Systemic spill-over of bile acids. Eur J Clin Invest 13(6):433–437

    Article  PubMed  Google Scholar 

  • Velazquez-Villegas LA et al (2018) TGR5 signalling promotes mitochondrial fission and beige remodelling of white adipose tissue. Nat Commun 9(1):245

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wahlstrom A et al (2017) Crosstalk between bile acids and gut microbiota and its impact on farnesoid X receptor signalling. Dig Dis 35(3):246–250

    Article  PubMed  Google Scholar 

  • Wang H et al (1999) Endogenous bile acids are ligands for the nuclear receptor FXR/BAR. Mol Cell 3(5):543–553

    Article  CAS  PubMed  Google Scholar 

  • Wang YD et al (2008) FXR: a metabolic regulator and cell protector. Cell Res 18(11):1087–1095

    Article  CAS  PubMed  Google Scholar 

  • Watanabe M et al (2006) Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 439(7075):484–489

    Article  CAS  PubMed  Google Scholar 

  • Werling M et al (2015) Roux-en-Y gastric bypass surgery increases respiratory quotient and energy expenditure during food intake. PLoS One 10(6):e0129784

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wilson-Perez HE et al (2013a) Vertical sleeve gastrectomy is effective in two genetic mouse models of glucagon-like peptide 1 receptor deficiency. Diabetes 62(7):2380–2385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilson-Perez HE et al (2013b) The effect of vertical sleeve gastrectomy on food choice in rats. Int J Obes (Lond) 37(2):288–295

    Article  CAS  Google Scholar 

  • Wu Q et al (2013) Changes of blood glucose and gastrointestinal hormones 4 months after Roux-en-Y gastric bypass surgery in Chinese obese type 2 diabetes patients with lower body mass index. J Diabetes Investig 4(2):214–221

    Article  CAS  PubMed  Google Scholar 

  • Xanthakos SA (2009) Nutritional deficiencies in obesity and after bariatric surgery. Pediatr Clin North Am 56(5):1105–1121

    Article  PubMed  PubMed Central  Google Scholar 

  • Yusta B et al (2017) Glucagon-like peptide-2 promotes gallbladder refilling via a TGR5-independent, GLP-2R-dependent pathway. Mol Metab 6(6):503–511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zaccardi F, Pitocco D, Ghirlanda G (2012) Bariatric surgery and prevention of type 2 diabetes. N Engl J Med 367(19):1863–1864. Author reply 1864

    PubMed  Google Scholar 

  • Zhai H et al (2018) 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 32:201–214

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang H et al (2009) Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci U S A 106(7):2365–2370

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang L et al (2012) Promotion of liver regeneration/repair by farnesoid X receptor in both liver and intestine in mice. Hepatology 56(6):2336–2343

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

We would like to apologize that we could not include all relevant publications in this review due to the space limitation. This work is supported by National Cancer Institute 2R01CA139158 and John Hench Foundation (W.H.), Shanghai Pujiang Program 17PJ1408800, and the National Natural Science Foundation of China 81773961 (L.D.).

Author Contributions

LD, ZF, and WH wrote the manuscript. YL and TH prepared the figures and table. EZ, LY, and ZW reviewed and revised the manuscript.

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Authors and Affiliations

  1. Department of Diabetes Complications and Metabolism, Diabetes & Metabolism Research Institute of City of Hope, Beckman Research Institute of City of Hope, Duarte, CA, USA

    Lili Ding, Zhipeng Fang, Yanjun Liu, Eryun Zhang & Wendong Huang

  2. Shanghai Key Laboratory of Compound Chinese Medicines and The Ministry of Education (MOE) Key Laboratory of Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China

    Lili Ding, Eryun Zhang, Li Yang & Zhengtao Wang

  3. Eugene and Roth Roberts Summer Student Academy, City of Hope, Duarte, CA, USA

    Tracy Huang

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  1. Lili Ding
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  2. Zhipeng Fang
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  4. Eryun Zhang
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  5. Tracy Huang
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  6. Li Yang
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  7. Zhengtao Wang
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  8. Wendong Huang
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Correspondence to Wendong Huang .

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Editors and Affiliations

  1. University of Perugia, School of Medicine, Perugia, Italy

    Stefano Fiorucci

  2. S.C. Gastroenterologia, Azienda Ospedaliera di Perugia, Perugia, Italy

    Eleonora Distrutti

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Ding, L. et al. (2019). Targeting Bile Acid-Activated Receptors in Bariatric Surgery. In: Fiorucci, S., Distrutti, E. (eds) Bile Acids and Their Receptors. Handbook of Experimental Pharmacology, vol 256. Springer, Cham. https://doi.org/10.1007/164_2019_229

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