Skip to main content
SpringerLink
Log in

Gastric Bypass with Different Biliopancreatic Limb Lengths Results in Similar Post-absorptive Metabolomics Profiles

  • Original Contributions
  • Published:
Obesity Surgery Aims and scope Submit manuscript

Abstract

Background/Aim

Roux-en-Y gastric bypass (RYGB) with a long biliopancreatic limb (BPL) was demonstrated to further improve type 2 diabetes (T2D) outcomes. Whether benefits occur at the cost of a negative impact on nutrient absorption is a matter of debate. Our aim was to evaluate the impact of RYGB BPL length on short-term nutrient absorption.

Methods

Subjects (N = 20) submitted to RYGB with a 2 m BPL (n = 11) or standard BPL (60–100 cm) (n = 9) 4.2 ± 0.4 years earlier underwent a mixed meal tolerance test. Plasma metabolites were analyzed at baseline and after meal by nuclear magnetic resonance (NMR) spectroscopy. Spectra were subject to multivariate analysis (MVA). Partial least square discriminant analysis (PLS-DA) was used to identify metabolites responsible for group discrimination.

Results

Principal component analysis and PLS-DA showed a clear separation between plasma metabolites before and 30 min after meal intake in both groups. The metabolites responsible for differences between time points were glucose and branched-chain amino acids. A complete overlap in metabolite species and concentrations was observed at 0 and 30 min time points for both groups, while acetate levels 120 min after the meal intake were significantly higher in subjects submitted to RYGB with a 2-m-long BPL as compared to the group submitted to the standard RYGB procedure.

Conclusions

Post-prandial plasma metabolomics profiles suggest that a 2-m-long BLP RYGB does not have a negative impact on acute metabolite absorption. RYGB BPL length seems to influence post-prandial acetate levels, which could contribute to the additional positive metabolic outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Kizy S, Jahansouz C, Wirth K, et al. Bariatric surgery: a perspective for primary care. Diabetes Spectr. 2017;30(4):265–76.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Angrisani L, Santonicola A, Iovino P, et al. Bariatric surgery and endoluminal procedures: IFSO Worldwide Survey 2014. Obes Surg. 2017;27(9):2279–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Nudel J, Sanchez VM. Surgical management of obesity. Metab Clin Exp. 2019;92:206–16.

    Article  CAS  PubMed  Google Scholar 

  4. Nora M, Guimaraes M, Almeida R, et al. Metabolic laparoscopic gastric bypass for obese patients with type 2 diabetes. Obes Surg. 2011;21(11):1643–9.

    Article  PubMed  Google Scholar 

  5. Koliaki C, Liatis S, le Roux CW, et al. The role of bariatric surgery to treat diabetes: current challenges and perspectives. BMC Endocr Disord. 2017;17(1):50.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Goldfine AB, Patti ME. Diabetes improvement following Roux-en-Y gastric bypass: understanding dynamic changes in insulin secretion and action. Diabetes. 2014;63(5):1454–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Maciejewski ML, Arterburn DE, Van Scoyoc L, et al. Bariatric surgery and long-term durability of weight loss. JAMA Surg. 2016;151(11):1046–55.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Noria SF, Grantcharov T. Biological effects of bariatric surgery on obesity-related comorbidities. Can J Surg. 2013;56(1):47–57.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Jakobsen GS, Smastuen MC, Sandbu R, et al. Association of bariatric surgery vs medical obesity treatment with long-term medical complications and obesity-related comorbidities. Jama. 2018 Jan 16;319(3):291–301.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Ionut V, Bergman RN. Mechanisms responsible for excess weight loss after bariatric surgery. J Diabetes Sci Technol. 2011;5(5):1263–82.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Rubino F, Forgione A, Cummings DE, et al. The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes. Ann Surg. 2006;244(5):741–9.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Mingrone G, Castagneto-Gissey L. Mechanisms of early improvement/resolution of type 2 diabetes after bariatric surgery. Diabetes Metab. 2009;35(6 Pt 2):518–23.

    Article  CAS  PubMed  Google Scholar 

  13. Svanevik M, Risstad H, Hofso D, et al. Perioperative outcomes of proximal and distal gastric bypass in patients with BMI ranged 50-60 kg/m(2)—a double-blind, randomized controlled trial. Obes Surg. 2015;25(10):1788–95.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Nelson WK, Fatima J, Houghton SG, et al. The malabsorptive very, very long limb Roux-en-Y gastric bypass for super obesity: results in 257 patients. Surgery. 2006;140(4):517–22. discussion 22-3

    Article  PubMed  Google Scholar 

  15. Kaska L, Kobiela J, Proczko M, et al. Does the length of the biliary limb influence medium-term laboratory remission of type 2 diabetes mellitus after Roux-en-Y gastric bypass in morbidly obese patients? Wideochirurgia i inne techniki maloinwazyjne = Videosurgery and other miniinvasive techniques. 2014;9(1):31-39.

  16. Leifsson BG, Gislason HG. Laparoscopic Roux-en-Y gastric bypass with 2-metre long biliopancreatic limb for morbid obesity: technique and experience with the first 150 patients. Obes Surg. 2005;15(1):35–42.

    Article  PubMed  Google Scholar 

  17. Nora M, Morais T, Almeida R, et al. Should Roux-en-Y gastric bypass biliopancreatic limb length be tailored to achieve improved diabetes outcomes? Medicine (Baltimore). 2017;96(48):e8859.

    Article  Google Scholar 

  18. Patricio BG, Morais T, Guimaraes M, et al. Gut hormone release after gastric bypass depends on the length of the biliopancreatic limb. Int J Obes. 2019;43(5):1009–18.

    Article  CAS  Google Scholar 

  19. Kiela PR, Ghishan FK. Physiology of intestinal absorption and secretion. Best Pract Res Clin Gastroenterol. 2016;30(2):145–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Goodman BE. Insights into digestion and absorption of major nutrients in humans. Adv Physiol Educ. 2010;34(2):44–53.

    Article  PubMed  Google Scholar 

  21. Wewer Albrechtsen NJ, Junker AE, Christensen M, et al. Hyperglucagonemia correlates with plasma levels of non-branched-chain amino acids in patients with liver disease independent of type 2 diabetes. Am J Physiol Gastrointest Liver Physiol. 2018;314(1):G91–g6.

    Article  PubMed  CAS  Google Scholar 

  22. Wishart DS, Feunang YD, Marcu A, et al. HMDB 4.0: the human metabolome database for 2018. Nucleic Acids Res. 2018;46(D1):D608–d17.

    Article  CAS  PubMed  Google Scholar 

  23. Jarak I, Carrola J, Barros AS, et al. From the cover: metabolism modulation in different organs by silver nanoparticles: an NMR metabolomics study of a mouse model. Toxicol Sci. 2017;159(2):422–35.

    Article  CAS  PubMed  Google Scholar 

  24. Savorani F, Tomasi G, Engelsen SB. icoshift: a versatile tool for the rapid alignment of 1D NMR spectra. J Magn Reson. 2010;202(2):190–202.

    Article  CAS  PubMed  Google Scholar 

  25. Dieterle F, Ross A, Schlotterbeck G, et al. Probabilistic quotient normalization as robust method to account for dilution of complex biological mixtures. Application in 1H NMR metabonomics. Anal Chem. 2006;78(13):4281–90.

    Article  CAS  PubMed  Google Scholar 

  26. Triba MN, Le Moyec L, Amathieu R, et al. PLS/OPLS models in metabolomics: the impact of permutation of dataset rows on the K-fold cross-validation quality parameters. Mol BioSyst. 2015;11(1):13–9.

    Article  CAS  PubMed  Google Scholar 

  27. Čuperlović-Culf M. NMR metabolomics in cancer research: Elsevier; 2012.

    Google Scholar 

  28. Abdul Rahim MBH, Chilloux J, Martinez-Gili L, et al. Diet-induced metabolic changes of the human gut microbiome: importance of short-chain fatty acids, methylamines and indoles. Acta Diabetol. 2019;56(5):493–500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Tebani A, Bekri S. Paving the way to precision nutrition through metabolomics. Front Nutr. 2019;6(41). https://doi.org/10.3389/fnut.2019.00041.

  30. Johnson CH, Ivanisevic J, Siuzdak G. Metabolomics: beyond biomarkers and towards mechanisms. Nat Rev Mol Cell Biol. 2016;17(7):451–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Samczuk P, Ciborowski M, Kretowski A. Application of metabolomics to study effects of bariatric surgery. J Diabetes Res. 2018:6270875.

  32. Arora T, Velagapudi V, Pournaras DJ, et al. Roux-en-Y gastric bypass surgery induces early plasma metabolomic and lipidomic alterations in humans associated with diabetes remission. PLoS One. 2015;10(5):e0126401.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Wijayatunga NN, Sams VG, Dawson JA, et al. Roux-en-Y gastric bypass surgery alters serum metabolites and fatty acids in patients with morbid obesity. Diabetes Metab Res Rev. 2018;34(8):e3045.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Wang Q, Holmes MV, Davey Smith G, et al. Genetic support for a causal role of insulin resistance on circulating branched-chain amino acids and inflammation. Diabetes Care. 2017 Dec;40(12):1779–86.

    Article  CAS  PubMed  Google Scholar 

  35. Wang TJ, Larson MG, Vasan RS, et al. Metabolite profiles and the risk of developing diabetes. Nat Med. 2011 Apr;17(4):448–53.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Nora M, Guimaraes M, Almeida R, et al. Excess body mass index loss predicts metabolic syndrome remission after gastric bypass. Diabetol Metab Syndr. 2014 Jan 2;6(1):1.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Gralka E, Luchinat C, Tenori L, et al. Metabolomic fingerprint of severe obesity is dynamically affected by bariatric surgery in a procedure-dependent manner. Am J Clin Nutr. 2015 Dec;102(6):1313–22.

    Article  CAS  PubMed  Google Scholar 

  38. Canfora EE, Blaak EE. Acetate: a diet-derived key metabolite in energy metabolism: good or bad in context of obesity and glucose homeostasis? Curr Opin Clin Nutr Metab Care. 2017 Nov;20(6):477–83.

    Article  CAS  PubMed  Google Scholar 

  39. Ríos-Covián D, Ruas-Madiedo P, Margolles A, et al. Intestinal short chain fatty acids and their link with diet and human health. Front Microbiol. 2016;7:185.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Perry RJ, Peng L, Barry NA, et al. Acetate mediates a microbiome-brain-beta-cell axis to promote metabolic syndrome. Nature. 2016;534(7606):213–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. den Besten G, van Eunen K, Groen AK, et al. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res. 2013;54(9):2325–40.

    Article  CAS  Google Scholar 

  42. Lim J, Henry CJ, Haldar S. Vinegar as a functional ingredient to improve postprandial glycemic control—human intervention findings and molecular mechanisms. Mol Nutr Food Res. 2016;60(8):1837–49.

    Article  CAS  PubMed  Google Scholar 

  43. Hernandez MAG, Canfora EE, Jocken JWE, et al. The short-chain fatty acid acetate in body weight control and insulin sensitivity. Nutrients. 2019;18:11(8).

    Google Scholar 

  44. Stinkens R, Goossens GH, Jocken JW, et al. Targeting fatty acid metabolism to improve glucose metabolism. Obes Rev. 2015;16(9):715–57.

    Article  CAS  PubMed  Google Scholar 

  45. Fernandes J, Vogt J, Wolever TM. Intravenous acetate elicits a greater free fatty acid rebound in normal than hyperinsulinaemic humans. Eur J Clin Nutr. 2012;66(9):1029–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. van der Beek CM, Canfora EE, Lenaerts K, et al. Distal, not proximal, colonic acetate infusions promote fat oxidation and improve metabolic markers in overweight/obese men. Clin Sci. 2016;130(22):2073–82.

    Article  Google Scholar 

  47. Freeland KR, Wolever TM. Acute effects of intravenous and rectal acetate on glucagon-like peptide-1, peptide YY, ghrelin, adiponectin and tumour necrosis factor-alpha. Br J Nutr. 2010;103(3):460–6.

    Article  CAS  PubMed  Google Scholar 

  48. Frost G, Sleeth ML, Sahuri-Arisoylu M, et al. The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat Commun. 2014;5:3611.

    Article  CAS  PubMed  Google Scholar 

  49. Smith PM, Howitt MR, Panikov N, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013;341(6145):569–73.

    Article  CAS  PubMed  Google Scholar 

  50. Soliman ML, Combs CK, Rosenberger TA. Modulation of inflammatory cytokines and mitogen-activated protein kinases by acetate in primary astrocytes. J Neuroimmune Pharmacol. 2013;8(1):287–300.

    Article  PubMed  Google Scholar 

  51. Kobayashi M, Mikami D, Kimura H, et al. Short-chain fatty acids, GPR41 and GPR43 ligands, inhibit TNF-alpha-induced MCP-1 expression by modulating p38 and JNK signaling pathways in human renal cortical epithelial cells. Biochem Biophys Res Commun. 2017;486(2):499–505.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Authors would like to thank Sandra Tavares (Centro Hospitalar de Entre o Douro e Vouga, Santa Maria da Feira, Portugal), Bárbara Patrício (UMIB, Porto, Portugal), and Tiago Morais (UMIB, Porto, Portugal), for their assistance during the MMTT.

Funding

The study was funded by grants from Foundation for Science and Technology (FCT) Portugal (UID/Multi/00215/2019). JJH holds an unrestricted grant from the NNF Center for Basic Metabolic Research, Copenhagen, Denmark. The NNF foundation Center for Basic Metabolic Research is an independent research institution at the University of Copenhagen, Denmark.

Author information

Authors and Affiliations

  1. Biology and Genetics of Reproduction, Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Porto, Portugal

    Ivana Jarak, Pedro F. Oliveira & Marco G. Alves

  2. Endocrine, Cardiovascular & Metabolic Research, Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Porto, Portugal

    Sofia S. Pereira, Marta Guimarães & Mariana P. Monteiro

  3. Department of Anatomy, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Jorge Viterbo Ferreira 228, Building 1.3, 4050-313, Porto, Portugal

    Sofia S. Pereira, Marta Guimarães & Mariana P. Monteiro

  4. Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Porto, Portugal

    Sofia S. Pereira & Pedro F. Oliveira

  5. Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal

    Sofia S. Pereira

  6. Department of Life Sciences, Faculty of Science and Technology (FCTUC), University of Coimbra, Coimbra, Portugal

    Rui A. Carvalho

  7. Department of Microscopy, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal

    Pedro F. Oliveira & Marco G. Alves

  8. Department of General Surgery, Centro Hospitalar de Entre o Douro e Vouga, Santa Maria da Feira, Portugal

    Marta Guimarães & Mário Nora

  9. Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Nicolai J. Wewer Albrechtsen & Jens J. Holst

  10. Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2100, Copenhagen, Denmark

    Nicolai J. Wewer Albrechtsen & Jens J. Holst

  11. Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark

    Nicolai J. Wewer Albrechtsen

Authors
  1. Ivana Jarak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sofia S. Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rui A. Carvalho
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pedro F. Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marco G. Alves
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marta Guimarães
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nicolai J. Wewer Albrechtsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jens J. Holst
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Mário Nora
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Mariana P. Monteiro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mariana P. Monteiro.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethics

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jarak, I., Pereira, S.S., Carvalho, R.A. et al. Gastric Bypass with Different Biliopancreatic Limb Lengths Results in Similar Post-absorptive Metabolomics Profiles. OBES SURG 30, 1068–1078 (2020). https://doi.org/10.1007/s11695-019-04294-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11695-019-04294-5

Keywords

Search

Navigation