Top

Published in:

20-06-2022 | Obesity | Pathogenesis of Type 2 Diabetes and Insulin Resistance (M-E Patti, Section Editor)

Gut Factors Mediating the Physiological Impact of Bariatric Surgery

Authors: Maigen Bethea, Darleen A. Sandoval

Published in: Current Diabetes Reports | Issue 8/2022

Abstract

Despite decades of obesity research and various public health initiatives, obesity remains a major public health concern. Our most drastic but most effective treatment of obesity is bariatric surgery with weight loss and improvements in co-morbidities, including resolution of type 2 diabetes (T2D). However, the mechanisms by which surgery elicits metabolic benefits are still not well understood. One proposed mechanism is through signals generated by the intestine (nutrients, neuronal, and/or endocrine) that communicate nutrient status to the brain. In this review, we discuss the contributions of gut-brain communication to the physiological regulation of body weight and its impact on the success of bariatric surgery. Advancing our understanding of the mechanisms that drive bariatric surgery-induced metabolic benefits will ultimately lead to the identification of novel, less invasive strategies to treat obesity.

Buchwald H, Estok R, Fahrbach K, Banel D, Jensen MD, Pories WJ, et al. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med. 2009; 122:248–256 e5. https://doi.org/10.1016/j.amjmed.2008.09.041

Schauer PR, Kashyap SR, Wolski K, Brethauer SA, Kirwan JP, Pothier CE, et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med 2012;366:1567–76. https://doi.org/10.1056/NEJMoa1200225

Welbourn R, Hollyman M, Kinsman R, Dixon J, Liem R, Ottosson J, et al. Bariatric surgery worldwide: baseline demographic description and one-year outcomes from the Fourth IFSO Global Registry Report 2018. Obes Surg Obes Surg. 2019;29:782–95. https://doi.org/10.1007/S11695-018-3593-1.CrossRefPubMed

Sandoval DA. Mechanisms for the metabolic success of bariatric surgery. J Neuroendocr. 2019; 31:e12708. https://doi.org/10.1111/jne.12708

Li J, Lai D, Wu D. Laparoscopic Roux-en-Y gastric bypass versus laparoscopic sleeve gastrectomy to treat morbid obesity-related comorbidities: a systematic review and meta-analysis. Obes Surg Springer; 2016. p. 429–42. Doi: https://doi.org/10.1007/s11695-015-1996-9

Shoar S, Saber AA. Long-term and midterm outcomes of laparoscopic sleeve gastrectomy versus Roux-en-Y gastric bypass: a systematic review and meta-analysis of comparative studies. Surg Obes Relat Dis Elsevier. 2017;13:170–80. https://doi.org/10.1016/j.soard.2016.08.011.CrossRef

Peterli R, Wolnerhanssen BK, Peters T, Vetter D, Kroll D, Borbely Y, et al. Effect of laparoscopic sleeve gastrectomy vs laparoscopic roux-en-y gastric bypass onweight loss in patients with morbid obesity the sm-boss randomized clinical trial. JAMA - J Am Med Assoc. 2018;319:255–65. https://doi.org/10.1001/jama.2017.20897

Mahawar KK, Sharples AJ. Contribution of malabsorption to weight loss after Roux-en-Y Gastric Bypass: a systematic review. Obes. Surg. Springer New York LLC; 2017. p. 2194–206. https://doi.org/10.1007/s11695-017-2762-y

Evers SS, Sandoval DA, Seeley RJ. The physiology and molecular underpinnings of the effects of bariatric surgery on obesity and diabetes. Annu Rev Physiol Annu Rev Physiol. 2017;79:313–34. https://doi.org/10.1146/annurev-physiol-022516-034423.CrossRefPubMed

10.

Stefater MA, Perez-Tilve D, Chambers AP, Wilson-Perez HE, Sandoval DA, Berger J, et al. Sleeve gastrectomy induces loss of weight and fat mass in obese rats, but does not affect leptin sensitivity. Gastroenterology. 2010;138:2426–36, 2436 e1–3. https://doi.org/10.1053/j.gastro.2010.02.059

11.

Wilson-Perez HE, Chambers AP, Sandoval DA, Stefater MA, Woods SC, Benoit SC, et al. The effect of vertical sleeve gastrectomy on food choice in rats. Int J Obes. 2013; 37:288–95. https://doi.org/10.1038/ijo.2012.18

12.

Grayson BE, Schneider KM, Woods SC, Seeley RJ. Improved rodent maternal metabolism but reduced intrauterine growth after vertical sleeve gastrectomy. Sci Transl Med. 2013;5. https://doi.org/10.1126/scitranslmed.3006505

13.

Ahlman H, Nilsson O. The gut as the largest endocrine organ in the body. Ann Oncol. Elsevier; 2001;12.

14.

Sjölund K, Sandén G, Håkanson R, Sundler F. Endocrine cells in human intestine: an immunocytochemical study. Gastroenterology. 1983;85:1120–30.CrossRef

15.

Egerod KL, Engelstoft MS, Grunddal KV, Nøhr MK, Secher A, Sakata I, et al. A major lineage of enteroendocrine cells coexpress CCK, secretin, GIP, GLP-1, PYY, and neurotensin but not somatostatin. Endocrinology. 2012;153:5782–95. https://doi.org/10.1210/en.2012-1595.CrossRefPubMedPubMedCentral

16.

Grunddal KV, Ratner CF, Svendsen B, Sommer F, Engelstoft MS, Madsen AN, et al. Neurotensin is coexpressed, coreleased, and acts together with GLP-1 and PYY in enteroendocrine control of metabolism. Endocrinology. 2016;157:176–94. https://doi.org/10.1210/en.2015-1600.CrossRefPubMed

17.

Sykaras AG, Demenis C, Cheng L, Pisitkun T, McLaughlin JT, Fenton RA, et al. Duodenal CCK cells from male mice express multiple hormones including ghrelin. Endocrinol (United States). 2014;155:3339–51. https://doi.org/10.1210/en.2013-2165.CrossRef

18.

Fothergill LJ, Callaghan B, Hunne B, Bravo DM, Furness JB. Costorage of enteroendocrine hormones evaluated at the cell and subcellular levels in male mice. Endocrinology Oxford Academic. 2017;158:2113–23. https://doi.org/10.1210/en.2017-00243.CrossRef

19.

Duca FA, Waise TMZ, Peppler WT, Lam TKT. The metabolic impact of small intestinal nutrient sensing. Nat Commun Nature Publishing Group; 2021. p. 1–12. https://doi.org/10.1038/s41467-021-21235-y

20.

Furness JB. The enteric nervous system and neurogastroenterology. Nat. Rev. Gastroenterol. Hepatol. 2012. p. 286–94. https://doi.org/10.1038/nrgastro.2012.32

21.

Yoo BB, Mazmanian SK. The Enteric Network: Interactions between the Immune and Nervous Systems of the Gut. Immunity. 2017. p. 910–26. https://doi.org/10.1016/j.immuni.2017.05.011

22.

Furness JB. Types of neurons in the enteric nervous system. J Auton Nerv Syst. 2000;81:87–96. https://doi.org/10.1016/S0165-1838(00)00127-2.CrossRefPubMed

23.

Powley TL. Vagal input to the enteric nervous system. Gut Gut; 2000. https://doi.org/10.1136/gut.47.suppl_4.iv30

24.

Drokhlyansky E, Smillie CS, Van Wittenberghe N, Ericsson M, Griffin GK, Eraslan G, et al. The human and mouse enteric nervous system at single-cell resolution cell. Cell Press; 2020;182:1606–1622.e23. https://doi.org/10.1016/J.CELL.2020.08.003

25.

Zeisel A, Hochgerner H, Lönnerberg P, Johnsson A, Memic F, van der Zwan J, et al. Molecular architecture of the mouse nervous system. Cell Cell. 2018;174:999-1014.e22. https://doi.org/10.1016/j.cell.2018.06.021.CrossRefPubMed

26.

Wang YB, de Lartigue G, Page AJ. Dissecting the role of subtypes of gastrointestinal vagal afferents. Front Physiol Front; 2020. p. 643. https://doi.org/10.3389/fphys.2020.00643

27.

Berthoud HR, Neuhuber WL. Functional and chemical anatomy of the afferent vagal system. Aut Neurosci. 2000;85:1–17. https://doi.org/10.1016/S1566-0702(00)00215-0

28.

Berthoud HR, Blackshaw LA, Brookes SJH, Grundy D. Neuroanatomy of extrinsic afferents supplying the gastrointestinal tract. Neurogastroenterol Motil. John Wiley & Sons, Ltd; 2004. p. 28–33. https://doi.org/10.1111/j.1743-3150.2004.00471.x

29.

Peris-Sampedro F, Le May M V., Stoltenborg I, Schéle E, Dickson SL. A skeleton in the cupboard in ghrelin research: Where are the skinny dwarfs? J Neuroendocrinol J Neuroendocrinol; 2021. https://doi.org/10.1111/jne.13025

30.

Ayala JE, Bracy DP, James FD, Burmeister MA, Wasserman DH, Drucker DJ. Glucagon-like peptide-1 receptor knockout mice are protected from high-fat diet-induced insulin resistance. Endocrinology The Endocrine Society. 2010;151:4678–87. https://doi.org/10.1210/en.2010-0289.CrossRef

31.

Boey D, Lin S, Karl T, Baldock P, Lee N, Enriquez R, et al. Peptide YY ablation in mice leads to the development of hyperinsulinaemia and obesity. Diabetologia Diabetologia. 2006;49:1360–70. https://doi.org/10.1007/s00125-006-0237-0.CrossRefPubMed

32.

Moran TH, Katz LF, Plata-Salaman CR, Schwartz GJ. Disordered food intake and obesity in rats lacking cholecystokinin A receptors. Am J Physiol - Regul Integr Comp Physiol Am J Physiol; 1998;274. https://doi.org/10.1152/ajpregu.1998.274.3.r618

33.

Donovan MJ, Paulino G, Raybould HE. CCK(1) receptor is essential for normal meal patterning in mice fed high fat diet. Physiol Behav Physiol Behav. 2007;92:969–74. https://doi.org/10.1016/J.PHYSBEH.2007.07.003.CrossRefPubMed

34.

Guida C, Stephen SD, Watson M, Dempster N, Larraufie P, Marjot T, et al. PYY plays a key role in the resolution of diabetes following bariatric surgery in humans. EBioMedicine. Elsevier; 2019;40. https://doi.org/10.1016/J.EBIOM.2018.12.040

35.

Le Roux CW, Batterham RL, Aylwin SJB, Patterson M, Borg CM, Wynne KJ, et al. Attenuated peptide YY release in obese subjects is associated with reduced satiety. Endocrinology Endocrinology. 2006;147:3–8. https://doi.org/10.1210/en.2005-0972.CrossRefPubMed

36.

Verdich C, Toubro S, Buemann B, Lysgård Madsen J, Juul Holst J, Astrup A. The role of postprandial releases of insulin and incretin hormones in meal-induced satiety - Effect of obesity and weight reduction. Int J Obes Nature Publishing Group. 2001;25:1206–14. https://doi.org/10.1038/sj.ijo.0801655.CrossRef

37.

Knop FK, Aaboe K, Vilsbøll T, Vølund A, Holst JJ, Krarup T, et al. Impaired incretin effect and fasting hyperglucagonaemia characterizing type 2 diabetic subjects are early signs of dysmetabolism in obesity. Diabetes, Obes Metab. Diabetes Obes Metab; 2012;14:500–10. https://doi.org/10.1111/j.1463-1326.2011.01549.x

38.

Vilsbøll T, Krarup T, Sonne J, Madsbad S, Vølund A, Juul AG, et al. Incretin secretion in relation to meal size and body weight in healthy subjects and people with type 1 and type 2 diabetes mellitus. J Clin Endocrinol Metab. J Clin Endocrinol Metab; 2003;88:2706–13. https://doi.org/10.1210/jc.2002-021873

39.

Covasa M, Grahn J, Ritter RC. High fat maintenance diet attenuates hindbrain neuronal response to CCK. Regul Pept. 2000;86:83–8. https://doi.org/10.1016/s0167-0115(99)00084-1

40.

Page AJ, Kentish SJ. Plasticity of gastrointestinal vagal afferent satiety signals. Neurogastroenterol. Motil. Neurogastroenterol Motil; 2017. https://doi.org/10.1111/nmo.12973

41.

Sewaybricker LE, Schur EA. Is Bariatric Surgery Brain Surgery? Diabetes American Diabetes Association. 2021;70:1244–6. https://doi.org/10.2337/DBI21-0022.CrossRef

42.

Almby KE, Lundqvist MH, Abrahamsson N, Kvernby S, Fahlström M, Pereira MJ, et al. Effects of gastric bypass surgery on the brain: simultaneous assessment of glucose uptake, blood flow, neural activity, and cognitive function during normo- and hypoglycemia. Diabetes American Diabetes Association. 2021;70:1265–77. https://doi.org/10.2337/DB20-1172.CrossRef

43.

Zimmerman CA, Knight ZA. Layers of signals that regulate appetite. Curr Opin Neurobiol Curr Opin Neurobiol. 2020;64:79–88. https://doi.org/10.1016/j.conb.2020.03.007.CrossRefPubMed

44.

Moura-Assis A, Friedman JM, Velloso LA. Gut-to-brain signals in feeding control. Am J Physiol - Endocrinol Metab, 2021 p. E326–32. https://doi.org/10.1152/AJPENDO.00388.2020

45.

Kim KS, Seeley RJ, Sandoval DA. Signalling from the periphery to the brain that regulates energy homeostasis. Nat Rev Neurosci Nat Rev Neurosci; 2018. p. 185–96. https://doi.org/10.1038/nrn.2018.8

46.

Bobbioni-Harsch E, Huber O, Morel P, Chassot G, Lehmann T, Volery M, et al. Factors influencing energy intake and body weight loss after gastric bypass. Eur J Clin Nutr. 2002;56:551–6. https://doi.org/10.1038/sj.ejcn.1601357

47.

Dias MC, Ribeiro AG, Scabim VM, Faintuch J, Zilberstein B, Gama-Rodrigues JJ. Dietary intake of female bariatric patients after anti-obesity gastroplasty. Clin (Sao Paulo). 2006;61:93–8. https://doi.org/10.1590/s1807-59322006000200002

48.

Warde-Kamar J, Rogers M, Flancbaum L, Laferrere B. Calorie intake and meal patterns up to 4 years after Roux-en-Y gastric bypass surgery. Obes Surg. 2004;14:1070–9. https://doi.org/10.1381/0960892041975668

49.

Moize V, Geliebter A, Gluck ME, Yahav E, Lorence M, Colarusso T, et al. Obese patients have inadequate protein intake related to protein intolerance up to 1 year following Roux-en-Y gastric bypass. Obes Surg. 2003;13:23–8. Doi: https://doi.org/10.1381/096089203321136548

50.

Trostler N, Mann A, Zilberbush N, Charuzi II, Avinoach E. Nutrient intake following vertical banded gastroplasty or gastric bypass. Obes Surg. 1995; 5:403–10. https://doi.org/10.1381/096089295765557502

51.

Naslund I, Jarnmark I, Andersson H. Dietary intake before and after gastric bypass and gastroplasty for morbid obesity in women. Int J Obes. 1988;12:503–13.

52.

Brolin RE, Robertson LB, Kenler HA, Cody RP. Weight loss and dietary intake after vertical banded gastroplasty and Roux-en-Y gastric bypass. Ann Surg. 1994;220:782–90. https://doi.org/10.1097/00000658-199412000-00012

53.

Zheng H, Shin AC, Lenard NR, Townsend RL, Patterson LM, Sigalet DL, et al. Meal patterns, satiety, and food choice in a rat model of Roux-en-Y gastric bypass surgery. Am J Physiol Regul Integr Comp Physiol. 2009; 297:R1273–82. https://doi.org/10.1152/ajpregu.00343.2009

54.

Ullrich J, Ernst B, Wilms B, Thurnheer M, Schultes B. Roux-en y gastric bypass surgery reduces hedonic hunger and improves dietary habits in severely obese subjects. Obes Surg Obes Surg. 2013;23:50–5. https://doi.org/10.1007/s11695-012-0754-5.CrossRefPubMed

55.

Sista F, Abruzzese V, Clementi M, Guadagni S, Montana L, Carandina S. Resolution of type 2 diabetes after sleeve gastrectomy: a 2-step hypothesis. Surg Obes Relat Dis. Surg Obes Relat Dis; 2018;14:284–90. https://doi.org/10.1016/j.soard.2017.12.009

56.

Braghetto I, Lanzarini E, Korn O, Valladares H, Molina JC, Henriquez A. Manometric changes of the lower esophageal sphincter after sleeve gastrectomy in obese patients. Obes Surg Obes Surg. 2010;20:357–62. https://doi.org/10.1007/s11695-009-0040-3.CrossRefPubMed

57.

Chambers AP, Smith EP, Begg DP, Grayson BE, Sisley S, Greer T, et al. Regulation of gastric emptying rate and its role in nutrient-induced GLP-1 secretion in rats after vertical sleeve gastrectomy. Am J Physiol Endocrinol Metab. 2014; 306:E424–32. https://doi.org/10.1152/ajpendo.00469.2013

58.

Chambers AP, Sorrell JE, Haller A, Roelofs K, Hutch CR, Kim KS, et al. The role of pancreatic preproglucagon in glucose homeostasis in mice. Cell Metab. Cell Press; 2017;25:927–934 e3. https://doi.org/10.1016/j.cmet.2017.02.008

59.

Svane MS, Bojsen-Møller KN, Martinussen C, Dirksen C, Madsen JL, Reitelseder S, et al. Postprandial nutrient handling and gastrointestinal hormone secretion after roux-en-y gastric bypass vs sleeve gastrectomy. Gastroenterology. Elsevier; 2019;156.

60.

Dirksen C, Bojsen-Møller KN, Jørgensen NB, Jacobsen SH, Kristiansen VB, Naver LS, et al. Exaggerated release and preserved insulinotropic action of glucagon-like peptide-1 underlie insulin hypersecretion in glucose-tolerant individuals after Roux-en-Y gastric bypass. Diabetologia Diabetologia. 2013;56:2679–87. https://doi.org/10.1007/s00125-013-3055-1.CrossRefPubMed

61.

Le Roux CW, Borg C, Wallis K, Vincent RP, Bueter M, Goodlad R, et al. Gut hypertrophy after gastric bypass is associated with increased glucagon-like peptide 2 and intestinal crypt cell proliferation. Ann Surg. 2010;252:50–6. https://doi.org/10.1097/SLA.0b013e3181d3d21f.CrossRefPubMed

62.

Kulkarni B V., Lasance K, Sorrell JE, Lemen L, Woods SC, Seeley RJ, et al. The role of proximal versus distal stomach resection in the weight loss seen after vertical sleeve gastrectomy. Am J Physiol - Regul Integr Comp Physiol. Am J Physiol Regul Integr Comp Physiol; 2016;311:R979–87. https://doi.org/10.1152/ajpregu.00125.2016

63.

Tessier R, Ribeiro-Parenti L, Bruneau O, Khodorova N, Cavin J-B, Bado A, et al. Effect of different bariatric surgeries on dietary protein bioavailability in rats. American Physiological Society Bethesda, MD ; 2019;317:G592–601. https://doi.org/10.1152/AJPGI.00142.2019

64.

Stefater MA, Sandoval DA, Chambers AP, Wilsonpérez HE, Hofmann SM, Jandacek R, et al. Sleeve gastrectomy in rats improves postprandial lipid clearance by reducing intestinal triglyceride secretion. Gastroenterology. W.B. Saunders; 2011;141:939–949.e4. https://doi.org/10.1053/J.GASTRO.2011.05.008

65.

Ding L, Zhang E, Yang Q, Jin L, Sousa KM, Dong B, et al. Vertical sleeve gastrectomy confers metabolic improvements by reducing intestinal bile acids and lipid absorption in mice. Proc Natl Acad Sci. National Academy of Sciences; 2021;118:e2019388118. https://doi.org/10.1073/pnas.2019388118

66.

Korner J, Inabnet W, Conwell IM, Taveras C, Daud A, Olivero-Rivera L, et al. Differential effects of gastric bypass and banding on circulating gut hormone and leptin levels. Obesity Obesity (Silver Spring). 2006;14:1553–61. https://doi.org/10.1038/oby.2006.179.CrossRef

67.

Shin AC, Zheng H, Townsend RL, Sigalet DL, Berthoud HR. Meal-induced hormone responses in a rat model of roux-en-Y gastric bypass surgery. Endocrinology Endocrinology. 2010;151:1588–97. https://doi.org/10.1210/en.2009-1332.CrossRefPubMed

68.

Yousseif A, Emmanuel J, Karra E, Millet Q, Elkalaawy M, Jenkinson AD, et al. Differential effects of laparoscopic sleeve gastrectomy and laparoscopic gastric bypass on appetite, circulating acyl-ghrelin, peptide YY3-36 and active GLP-1 levels in non-diabetic humans. Obes Surg Obes Surg. 2014;24:241–52. https://doi.org/10.1007/s11695-013-1066-0.CrossRefPubMed

69.

Nannipieri M, Baldi S, Mari A, Colligiani D, Guarino D, Camastra S, et al. Roux-en-Y gastric bypass and sleeve gastrectomy: mechanisms of diabetes remission and role of gut hormones. J Clin Endocrinol Metab. J Clin Endocrinol Metab; 2013;98:4391–9. https://doi.org/10.1210/jc.2013-2538

70.

Jacobsen SH, Olesen SC, Dirksen C, Jørgensen NB, Bojsen-Møller KN, Kielgast U, et al. Changes in gastrointestinal hormone responses, insulin sensitivity, and beta-cell function within 2 weeks after gastric bypass in non-diabetic subjects. Obes Surg Springer. 2012;22:1084–96. https://doi.org/10.1007/s11695-012-0621-4.CrossRef

71.

Papamargaritis D, Le Roux CW. Do gut hormones contribute to weight loss and glycaemic outcomes after bariatric surgery? Nutrients. Multidisciplinary Digital Publishing Institute; 2020. p. 1–28. https://doi.org/10.3390/nu13030762

72.

Hutch CR, Sandoval DA. Physiological and molecular responses to bariatric surgery: markers or mechanisms underlying T2DM resolution? Ann. N. Y. Acad. Sci. Ann N Y Acad Sci; 2017. p. 5–19. https://doi.org/10.1111/nyas.13194

73.

Kim KS, Sandoval DA. Endocrine function after bariatric surgery. Compr Physiol Compr Physiol. 2017;7:783–98. https://doi.org/10.1002/cphy.c160019.CrossRefPubMed

74.

Pucci A, Cheung WH, Jones J, Manning S, Kingett H, Adamo M, et al. A case of severe anorexia, excessive weight loss and high peptide YY levels after sleeve gastrectomy. Endocrinol Diabetes Metab Case Reports. Endocrinol Diabetes Metab Case Rep; 2015; 2015. https://doi.org/10.1530/edm-15-0020

75.

Cavin JB, Couvelard A, Lebtahi R, Ducroc R, Arapis K, Voitellier E, et al. Differences in alimentary glucose absorption and intestinal disposal of blood glucose after Roux-en-Y gastric bypass vs sleeve gastrectomy. Gastroenterology. 2016;150:454-464.e9. https://doi.org/10.1053/j.gastro.2015.10.009.CrossRefPubMed

76.

Nausheen S, Shah IH, Pezeshki A, Sigalet DL, Chelikani PK. Effects of sleeve gastrectomy and ileal transposition, alone and in combination, on food intake, body weight, gut hormones, and glucose metabolism in rats. Am J Physiol - Endocrinol Metab. 2013;305:507–18. https://doi.org/10.1152/ajpendo.00130.2013.CrossRef

77.

Li F, Peng Y, Zhang M, Yang P, Qu S. Sleeve gastrectomy activates the GLP-1 pathway in pancreatic β cells and promotes GLP-1-expressing cells differentiation in the intestinal tract. Mol Cell Endocrinol. 2016;436:33–40. https://doi.org/10.1016/j.mce.2016.07.019.CrossRefPubMed

78.

Kim K-S, E Peck BC, Hung Y-H, Koch-Laskowski K, Wood L, Spence JR, et al. Vertical sleeve gastrectomy induces enteroendocrine cell differentiation of intestinal stem cells through farnesoid x receptor activation. bioRxiv. Cold Spring Harbor Laboratory; 2021;2021.04.22.440705. https://doi.org/10.1101/2021.04.22.440705

79.

Chambers AP, Jessen L, Ryan KK, Sisley S, Wilson-Pérez HE, Stefater MA, et al. Weight-independent changes in blood glucose homeostasis after gastric bypass or vertical sleeve gastrectomy in rats. Gastroenterology. NIH Public Access; 2011;141:950. https://doi.org/10.1053/J.GASTRO.2011.05.050

80.

Hindsø M, MS S, N H, JJ H, S M, KN B-M, et al. The role of GLP-1 in postprandial glucose metabolism after bariatric surgery: a narrative review of human GLP-1 receptor antagonist studies. Surg Obes Relat Dis. Surg Obes Relat Dis; 2021;17:1383–91. https://doi.org/10.1016/J.SOARD.2021.01.041

81.

Wilson-Pérez HE, Chambers AP, Ryan KK, Li B, Sandoval DA, Stoffers D, et al. Vertical sleeve gastrectomy is effective in two genetic mouse models of glucagon-like Peptide 1 receptor deficiency. Diabetes. Diabetes; 2013;62:2380–5. https://doi.org/10.2337/db12-1498

82.

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; 3:191–201. https://doi.org/10.1016/j.molmet.2013.11.010

83.

Kim K-S, Hutch CR, Wood L, Magrisso IJ, Seeley RJ, Sandoval DA. Glycemic effect of pancreatic preproglucagon in mouse sleeve gastrectomy.https://doi.org/10.1172/jci.insight.129452

84.

Hajnal A, Kovacs P, Ahmed T, Meirelles K, Lynch CJ, Cooney RN. Gastric bypass surgery alters behavioral and neural taste functions for sweet taste in obese rats. Am J Physiol - Gastrointest Liver Physiol. American Physiological Society; 2010;299:G967. https://doi.org/10.1152/ajpgi.00070.2010

85.

CHAMBERS AP, KIRCHNER H, WILSON–PEREZ HE, WILLENCY JA, HALE JE, GAYLINN BD, et al. The effects of vertical sleeve gastrectomy in rodents are ghrelin independent. Gastroenterology. NIH Public Access; 2013;144:50. https://doi.org/10.1053/J.GASTRO.2012.09.009

86.

Chandarana K, Gelegen C, Karra E, Choudhury AI, Drew ME, Fauveau V, et al. Diet and gastrointestinal bypass-induced weight loss: the roles of ghrelin and peptide YY. Diabetes Diabetes. 2011;60:810–8. https://doi.org/10.2337/DB10-0566.CrossRefPubMed

87.

Finan B, Yang B, Ottaway N, Smiley DL, Ma T, Clemmensen C, et al. A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents. Nat Med Nature Publishing Group. 2015;21:27–36. https://doi.org/10.1038/nm.3761.CrossRef

88.

Jones B, Sands C, Alexiadou K, Minnion J, Tharakan G, Behary P, et al. The metabolomic effects of tripeptide gut hormone infusion compared to Roux-en-Y gastric bypass and caloric restriction. J Clin Endocrinol Metab. 2021;XX:1–16. https://doi.org/10.1210/clinem/dgab608

89.

Gimeno RE, Briere DA, Seeley RJ. Leveraging the gut to treat metabolic disease. Cell Metab. 2020. p. 679–98. https://doi.org/10.1016/j.cmet.2020.02.014

90.

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 Springer. 2016;26:957–65. https://doi.org/10.1007/s11695-015-1834-0.CrossRef

91.

Patti ME, Houten SM, Bianco AC, Bernier R, Larsen PR, Holst JJ, et al. Serum bile acids are higher in humans with prior gastric bypass: potential contribution to improved glucose and lipid metabolism. Obesity. John Wiley & Sons, Ltd; 2009;17:1671–7. https://doi.org/10.1038/oby.2009.102

92.

Myronovych A, Kirby M, Ryan KK, Zhang W, Jha P, Setchell KD, et al. Vertical sleeve gastrectomy reduces hepatic steatosis while increasing serum bile acids in a weight-loss-independent manner. Obesity. John Wiley & Sons, Ltd; 2014;22:390–400. https://doi.org/10.1002/oby.20548

93.

Stofan M, Guo GL. Bile Acids and FXR: Novel Targets for Liver Diseases. Front. Med. Frontiers; 2020. p. 544. https://doi.org/10.3389/fmed.2020.00544

94.

Duboc H, Taché Y, Hofmann AF. The bile acid TGR5 membrane receptor: From basic research to clinical application. Dig. Liver Dis. Elsevier; 2014. p. 302–12. https://doi.org/10.1016/j.dld.2013.10.021

95.

Castellanos-Jankiewicz A, Guzmán-Quevedo O, Fénelon VS, Zizzari P, Quarta C, Bellocchio L, et al. Hypothalamic bile acid-TGR5 signaling protects from obesity. Cell Metab Elsevier. 2021;33:1483-1492.e10. https://doi.org/10.1016/j.cmet.2021.04.009.CrossRef

96.

Ding L, Sousa KM, Jin L, Dong B, Kim B-WW, Ramirez R, et al. Vertical sleeve gastrectomy activates GPBAR-1/TGR5 to sustain weight loss, improve fatty liver, and remit insulin resistance in mice. Hepatology. Hepatology; 2016;64:760–73. https://doi.org/10.1002/HEP.28689

97.

McGavigan AK, Garibay D, Henseler ZM, Chen J, Bettaieb A, Haj FG, et al. TGR5 contributes to glucoregulatory improvements after vertical sleeve gastrectomy in mice. Gut Gut. 2017;66:226–34. https://doi.org/10.1136/GUTJNL-2015-309871.CrossRefPubMed

98.

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 NIH Public Access. 2014;509:183–8. https://doi.org/10.1038/nature13135.CrossRef

99.

Clifford BL, Sedgeman LR, Williams KJ, Morand P, Cheng A, Jarrett KE, et al. FXR activation protects against NAFLD via bile-acid-dependent reductions in lipid absorption. Cell Metab Cell Metab. 2021;33:1671-1684.e4. https://doi.org/10.1016/J.CMET.2021.06.012.CrossRefPubMed

100.

Myronovych A, Salazar-Gonzalez R-MM, Ryan KK, Miles L, Zhang W, Jha P, et al. The role of small heterodimer partner in nonalcoholic fatty liver disease improvement after sleeve gastrectomy in mice. Obesity. Obesity (Silver Spring); 2014;22:2301–11. https://doi.org/10.1002/OBY.20890

101.

Inagaki T, Choi M, Moschetta A, Peng L, Cummins CL, McDonald JG, et al. Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. Cell Metab Elsevier. 2005;2:217–25. https://doi.org/10.1016/j.cmet.2005.09.001.CrossRef

102.

DePaoli AM, Zhou M, Kaplan DD, Hunt SC, Adams TD, Marc Learned R, et al. FGF19 analog as a surgical factor mimetic that contributes to metabolic effects beyond glucose homeostasis. Diabetes American Diabetes Association. 2019;68:1315–28. https://doi.org/10.2337/db18-1305.CrossRef

103.

Gómez-Ambrosi J, Gallego-Escuredo JM, Catalán V, Rodríguez A, Domingo P, Moncada R, et al. FGF19 and FGF21 serum concentrations in human obesity and type 2 diabetes behave differently after diet- or surgically-induced weight loss. Clin Nutr Elsevier. 2017;36:861–8. https://doi.org/10.1016/j.clnu.2016.04.027.CrossRef

104.

Haluzíková D, Lacinová Z, Kaválková P, Drápalová J, Křížová J, Bártlová M, et al. Laparoscopic sleeve gastrectomy differentially affects serum concentrations of FGF-19 and FGF-21 in morbidly obese subjects. Obesity. John Wiley & Sons, Ltd; 2013;21:1335–42. https://doi.org/10.1002/oby.20208

105.

Lan T, Morgan DA, Rahmouni K, Sonoda J, Fu X, Burgess SC, et al. FGF19, FGF21, and an FGFR1/β-klotho-activating antibody act on the nervous system to regulate body weight and glycemia. Cell Metab Cell Metab. 2017;26:709-718.e3. https://doi.org/10.1016/j.cmet.2017.09.005.CrossRefPubMed

106.

Kir S, Beddow SA, Samuel VT, Miller P, Previs SF, Suino-Powell K, et al. FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis. Science (80- ). Science; 2011;331:1621–4. https://doi.org/10.1126/science.1198363

107.

Potthoff MJ, Boney-Montoya J, Choi M, He T, Sunny NE, Satapati S, et al. FGF15/19 regulates hepatic glucose metabolism by inhibiting the CREB-PGC-1α pathway. Cell Metab Cell Metab. 2011;13:729–38. https://doi.org/10.1016/j.cmet.2011.03.019.CrossRefPubMed

108.

Bozadjieva-Kramer N, Shin JH, Shao Y, Gutierrez-Aguilar R, Li Z, Heppner KM, et al. Intestinal-derived FGF15 protects against deleterious effects of vertical sleeve gastrectomy in mice. Nat Commun Nature Publishing Group. 2021;12:1–19. https://doi.org/10.1038/s41467-021-24914-y.CrossRef

109.

Myronovych A, Bhattacharjee J, Salazar-Gonzalez RM, Tan B, Mowery S, Ferguson D, et al. Assessment of the role of FGF15 in mediating the metabolic outcomes of murine vertical sleeve gastrectomy. Am J Physiol - Gastrointest Liver Physiol. 2020;319:G669–84. https://doi.org/10.1152/AJPGI.00175.2020.CrossRefPubMedCentral

110.

Mulla C, Goldfine M, Dreyfuss J, Houten S, Pan H, Pober, et al. Plasma FGF-19 levels are increased in patients with post-bariatric hypoglycemia. 2019;29:2092–9. https://doi.org/10.1007/S11695-019-03845-0

111.

Lundqvist MH, Almby K, Abrahamsson N, Eriksson JW. Is the brain a key player in glucose regulation and development of type 2 diabetes? Front. Physiol. Frontiers; 2019. p. 457. https://doi.org/10.3389/fphys.2019.00457

112.

Nogueiras R. The gut-brain axis: regulating energy balance independent of food intake. Eur. J. Endocrinol. Bioscientifica Ltd; 2021. p. R75–91. https://doi.org/10.1530/EJE-21-0277

113.

Chambers AP, Wilson-Perez HE, McGrath S, Grayson BE, Ryan KK, D’Alessio DA, et al. Effect of vertical sleeve gastrectomy on food selection and satiation in rats. Am J Physiol Endocrinol Metab. 2012/08/31. 2012;303:E1076–84. https://doi.org/10.1152/ajpendo.00211.2012

114.

Beutler LR, Chen Y, Ahn JS, Lin YC, Essner RA, Knight ZA. Dynamics of gut-brain communication underlying hunger. Neuron Cell Press. 2017;96:461-475.e5. https://doi.org/10.1016/j.neuron.2017.09.043.CrossRef

115.

Su Z, Alhadeff AL, Betley JN. Nutritive, post-ingestive signals are the primary regulators of AgRP neuron activity. Cell Rep Cell Press. 2017;21:2724–36. https://doi.org/10.1016/j.celrep.2017.11.036.CrossRef

116.

Goldstein N, McKnight AD, Carty JRE, Arnold M, Betley JN, Alhadeff AL. Hypothalamic detection of macronutrients via multiple gut-brain pathways. Cell Metab. 2021;33:676-687.e5.CrossRef

117.

Hankir MK, Seyfried F, Hintschich CA, Diep T-A, Kleberg K, Kranz M, et al. Gastric bypass surgery recruits a Gut PPAR-α-Striatal D1R Pathway to reduce fat appetite in obese rats. 2017; 25:335–44. https://doi.org/10.1016/J.CMET.2016.12.006

118.

Shin AC, Zheng H, Berthoud HR. Vagal innervation of the hepatic portal vein and liver is not necessary for Roux-en-Y gastric bypass surgery-induced hypophagia, weight loss, and hypermetabolism. Ann Surg. 2012;255:294–301.CrossRef

119.

Okafor PN, Lien C, Bairdain S, Simonson DC, Halperin F, Vernon AH, et al. Effect of vagotomy during Roux-en-Y gastric bypass surgery on weight loss outcomes. Obes Res Clin Pract. 2015;9:274–80. https://doi.org/10.1016/j.orcp.2014.09.005.CrossRefPubMed

120.

Hao Z, Townsend RL, Mumphrey MB, Patterson LM, Ye J, Berthoud HR. Vagal innervation of intestine contributes to weight loss After Roux-en-Y gastric bypass surgery in rats. Obes Surg. 2014;24:2145–51. https://doi.org/10.1007/s11695-014-1338-3

121.

Bai L, Mesgarzadeh S, Ramesh KS, Huey EL, Liu Y, Gray LA, et al. Genetic identification of vagal sensory neurons that control feeding. Cell. 2019;179:1129–1143 e23. https://doi.org/10.1016/j.cell.2019.10.031

122.

Kupari J, Haring M, Agirre E, Castelo-Branco G, Ernfors P. An atlas of vagal sensory neurons and their molecular specialization. Cell Rep. 2019; 27:2508–2523 e4. https://doi.org/10.1016/j.celrep.2019.04.096

123.

Brierley DI, Holt MK, Singh A, de Araujo A, McDougle M, Vergara M, et al. Central and peripheral GLP-1 systems independently suppress eating. Nat Metab 2021 32. Nature Publishing Group; 2021;3:258–73. https://doi.org/10.1038/s42255-021-00344-4

124.

Sisley S, Gutierrez-Aguilar R, Scott M, D’Alessio DA, Sandoval DA, Seeley RJ, et al. Neuronal GLP1R mediates liraglutide’s anorectic but not glucose-lowering effect. J Clin Invest. American Society for Clinical Investigation; 2014;124:2456–63. https://doi.org/10.1172/JCI72434

125.

Borgmann D, Ciglieri E, Biglari N, Brandt C, Cremer AL, Backes H, et al. Gut-brain communication by distinct sensory neurons differently controls feeding and glucose metabolism. Cell Metab. 2021;1466–1482.e7. https://doi.org/10.1016/j.cmet.2021.05.002

Title: Gut Factors Mediating the Physiological Impact of Bariatric Surgery
Authors: Maigen Bethea
Darleen A. Sandoval
Publication date: 20-06-2022
Publisher: Springer US
Keywords: Obesity
Obesity
Bariatric Surgery
Bariatric Surgery
Published in: Current Diabetes Reports / Issue 8/2022
Print ISSN: 1534-4827
Electronic ISSN: 1539-0829
DOI: https://doi.org/10.1007/s11892-022-01478-9

ACC 2024 Congress Coverage

Cardiology Video

Highlights from the ACC 2024 Congress

Watch now

Watch official videos from the ACC congress summarizing key highlights from the last year in heart failure, cardiomyopathies, valvular disease, pulmonary vascular disease, and pediatric cardiology.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

ACC 2024 Congress

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 8/2022

Psychosocial Needs for Newly Diagnosed Youth with Type 1 Diabetes and Their Families

Shift Work and Obesity Risk—Are There Sex Differences?

Evaluating Natural Experiments that Impact the Diabetes Epidemic: an Introduction to the NEXT-D3 Network

Metabolic Syndrome and Vascular-Associated Cognitive Impairment: a Focus on Preclinical Investigations