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A Pilot Study of Serum Sphingomyelin Dynamics in Subjects with Severe Obesity and Non-alcoholic Steatohepatitis after Sleeve Gastrectomy

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Abstract

Background

Non-alcoholic steatohepatitis (NASH) is present in a high percentage of obese patients undergoing bariatric surgery. A significant proportion of patients still present NASH even after considerable weight loss and metabolic improvements after surgery.

Objective

To determine whether the changes in the serum lipidome after sleeve gastrectomy could be used to discriminate obese patients with NASH patients to those with non-alcoholic fatty liver (NAFL).

Methods

This study involved 24 patients with grade 3 obesity diagnosed with either NAFL (n = 8) or NASH (n = 16) using the non-invasive OWLiver assay. All patients suffering from NASH were re-evaluated 6 months after bariatric surgery using the OWLiver test to confirm NASH resolution. Serum lipid extracts were assessed at baseline and 6 months post surgery and were analyzed in an ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC-TOF-MS)-based platform.

Results

Lipidomic analysis revealed a differential sphingomyelin profile in patients with NASH resolution after sleeve gastrectomy. Certain serum sphingomyelin species were significantly higher at baseline in NASH patients in comparison to those with NAFL. Sphingomyelin profile of subjects with NASH resolution was similar to that for obese subjects with NAFL before bariatric surgery.

Conclusion

Our study indicates that the serum sphingomyelin levels could be related to the status of non-alcoholic fatty liver disease and that certain sphingomyelin species may be used for the follow-up of obese patients with NASH after sleeve gastrectomy.

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References

  1. Younossi ZM, Koenig AB, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64:73–84.

    Article  PubMed  Google Scholar 

  2. Younossi Z, Anstee QM, Marietti M, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2018;15:11–20.

    Article  PubMed  Google Scholar 

  3. Machado M, Marques-Vidal P, Cortez-Pinto H. Hepatic histology in obese patients undergoing bariatric surgery. J Hepatol. 2006;45:600–6.

    Article  PubMed  Google Scholar 

  4. Alqahtani A, Elahmedi M, Alswat K, et al. Features of nonalcoholic steatohepatitis in severely obese children and adolescents undergoing sleeve gastrectomy. Surg Obes Relat Dis. 2017;13:1599–609.

    Article  PubMed  Google Scholar 

  5. Lassailly G, Caiazzo R, Buob D, et al. Bariatric surgery reduces features of nonalcoholic steatohepatitis in morbidly obese patients. Gastroenterology. 2015;149:379–88. quiz e15–6

    Article  PubMed  Google Scholar 

  6. Klebanoff MJ, Corey KE, Chhatwal J, et al. Bariatric surgery for nonalcoholic steatohepatitis: a clinical and cost-effectiveness analysis. Hepatology. 2017;65:1156–64.

    Article  PubMed  Google Scholar 

  7. Caravatto PP, Cohen R. The role of metabolic surgery in non-alcoholic steatohepatitis improvement. Curr Atheroscler Rep. 2017;19:45.

    Article  PubMed  Google Scholar 

  8. Puri P, Baillie RA, Wiest MM, et al. A lipidomic analysis of nonalcoholic fatty liver disease. Hepatology. 2007;46:1081–90.

    Article  CAS  PubMed  Google Scholar 

  9. Puri P, Wiest MM, Cheung O, et al. The plasma lipidomic signature of nonalcoholic steatohepatitis. Hepatology. 2009;50:1827–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Anjani K, Lhomme M, Sokolovska N, et al. Circulating phospholipid profiling identifies portal contribution to NASH signature in obesity. J Hepatol. 2015;62:905–12.

    Article  CAS  PubMed  Google Scholar 

  11. Chiappini F, Coilly A, Kadar H, et al. Metabolism dysregulation induces a specific lipid signature of nonalcoholic steatohepatitis in patients. Sci Rep. 2017;7:46658.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Barr J, Caballeria J, Martinez-Arranz I, et al. Obesity-dependent metabolic signatures associated with nonalcoholic fatty liver disease progression. J Proteome Res. 2012;11:2521–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Mayo R, Crespo J, Martínez-Arranz I, et al. Metabolomic-based noninvasive serum test to diagnose nonalcoholic steatohepatitis: results from discovery and validation cohorts. Hepatol Commun. 2018;2:807–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Barr J, Vazquez-Chantada M, Alonso C, et al. Liquid chromatography-mass spectrometry-based parallel metabolic profiling of human and mouse model serum reveals putative biomarkers associated with the progression of nonalcoholic fatty liver disease. J Proteome Res. 2010;9:4501–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Alonso C, Fernandez-Ramos D, Varela-Rey M, et al. Metabolomic identification of subtypes of nonalcoholic steatohepatitis. Gastroenterology. 2017;152:1449–61 e7.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Cano A, Marino Z, Millet O, et al. A metabolomics signature linked to liver fibrosis in the serum of transplanted hepatitis C patients. Sci Rep. 2017;7:10497.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Liebisch G, Vizcaino JA, Kofeler H, et al. Shorthand notation for lipid structures derived from mass spectrometry. J Lipid Res. 2013;54:1523–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Martinez-Arranz I, Mayo R, Perez-Cormenzana M, et al. Enhancing metabolomics research through data mining. J Proteome. 2015;127:275–88.

    Article  CAS  Google Scholar 

  19. Babicki S, Arndt D, Marcu A, et al. Heatmapper: web-enabled heat mapping for all. Nucleic Acids Res. 2016;44:W147–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kotronen A, Seppanen-Laakso T, Westerbacka J, et al. Comparison of lipid and fatty acid composition of the liver, subcutaneous and intra-abdominal adipose tissue, and serum. Obesity (Silver Spring). 2010;18:937–44.

    Article  CAS  Google Scholar 

  21. Quehenberger O, Armando AM, Brown AH, et al. Lipidomics reveals a remarkable diversity of lipids in human plasma. J Lipid Res. 2010;51:3299–305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Rodriguez-Cuenca S, Pellegrinelli V, Campbell M, et al. Sphingolipids and glycerophospholipids - the “ying and yang” of lipotoxicity in metabolic diseases. Prog Lipid Res. 2017;66:14–29.

    Article  CAS  PubMed  Google Scholar 

  23. Pagadala M, Kasumov T, McCullough AJ, et al. Role of ceramides in nonalcoholic fatty liver disease. Trends Endocrinol Metab. 2012;23:365–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Iqbal J, Walsh MT, Hammad SM, et al. Sphingolipids and lipoproteins in health and metabolic disorders. Trends Endocrinol Metab. 2017;28:506–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Saito K, Uebanso T, Maekawa K, et al. Characterization of hepatic lipid profiles in a mouse model with nonalcoholic steatohepatitis and subsequent fibrosis. Sci Rep. 2015;5:12466.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Chiappini F, Desterke C, Bertrand-Michel J, et al. Hepatic and serum lipid signatures specific to nonalcoholic steatohepatitis in murine models. Sci Rep. 2016;6:31587.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Graessler J, Bornstein TD, Goel D, et al. Lipidomic profiling before and after Roux-en-Y gastric bypass in obese patients with diabetes. Pharmacogenomics J. 2014;14:201–7.

    Article  CAS  PubMed  Google Scholar 

  28. 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:e0126401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kayser BD, Lhomme M, Dao MC, et al. Serum lipidomics reveals early differential effects of gastric bypass compared with banding on phospholipids and sphingolipids independent of differences in weight loss. Int J Obes. 2017;41:917–25.

    Article  CAS  Google Scholar 

  30. Ramos-Molina B, Castellano-Castillo D, Alcaide Torres J, Pastor O, de Luna Diaz R, Salas-Salvado J, et al. Differential effects of restrictive and malabsorptive bariatric surgery procedures on the serum lipidome in obese subjects. J Clin Lipidol. 2018;S1933-2874(18)30307-6. https://doi.org/10.1016/j.jacl.2018.07.006.

  31. Davis S, Nehus E, Inge T, et al. Effect of bariatric surgery on urinary sphingolipids in adolescents with severe obesity. Surg Obes Relat Dis. 2018;14:446–51.

    Article  PubMed  Google Scholar 

  32. Kalinowski P, Paluszkiewicz R, Ziarkiewicz-Wroblewska B, et al. Liver function in patients with nonalcoholic fatty liver disease randomized to Roux-en-Y gastric bypass versus sleeve gastrectomy: a secondary analysis of a randomized clinical trial. Ann Surg. 2017;266:738–45.

    Article  PubMed  Google Scholar 

  33. Bril F, Millan L, Kalavalpalli S, et al. Use of a metabolomic approach to non-invasively diagnose nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2018;20:1702–9.

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was supported by the “Centros de Investigación Biomédica en Red” (CIBER) of the “Instituto de Salud Carlos III” (ISCIII) (CB06/03/0018), and research grants from ISCIII (PIE14/00031, PI14/00082, and PI15/01114), and co-financed by the European Regional Development Fund (ERDF). DCC was a recipient of a FPU predoctoral fellowship from Ministry of Education, Spain (13/04211). BRM was a recipient of a Sara Borrell postdoctoral fellowship, ISCIII, Spain (CD16/0003). FC was a recipient of the Nicolas Monardes Programme from SAS (C-0032-2016).

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Authors and Affiliations

  1. Unidad Gestión Clínica Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Campus de Teatinos s/n, 29010, Malaga, Spain

    Bruno Ramos-Molina, Daniel Castellano-Castillo, Fernando Cardona & Francisco J. Tinahones

  2. CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain

    Bruno Ramos-Molina, Daniel Castellano-Castillo, Fernando Cardona & Francisco J. Tinahones

  3. Unidad de Cuantificación y Caracterización Molecular, Servicio de Bioquímica Clínica, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, Madrid, Spain

    Oscar Pastor

  4. Unidad de Cirugía Metabólica, Hospital Universitario Virgen de la Victoria, Málaga, Spain

    Luis Ocaña-Wilhelmi

  5. Unidad Gestión Clínica Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Málaga, Spain

    Diego Fernández-García

  6. Unidad de Gestión Clínica de Aparato Digestivo, CIBERehd, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, Spain

    Manuel Romero-Gómez

Authors
  1. Bruno Ramos-Molina
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  2. Daniel Castellano-Castillo
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  3. Oscar Pastor
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  4. Luis Ocaña-Wilhelmi
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  5. Diego Fernández-García
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  6. Manuel Romero-Gómez
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  7. Fernando Cardona
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  8. Francisco J. Tinahones
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Corresponding author

Correspondence to Fernando Cardona.

Ethics declarations

All participants gave their written informed consent, and the study was reviewed and approved by the local ethics and research committee.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Ramos-Molina, B., Castellano-Castillo, D., Pastor, O. et al. A Pilot Study of Serum Sphingomyelin Dynamics in Subjects with Severe Obesity and Non-alcoholic Steatohepatitis after Sleeve Gastrectomy. OBES SURG 29, 983–989 (2019). https://doi.org/10.1007/s11695-018-3612-2

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  • DOI: https://doi.org/10.1007/s11695-018-3612-2

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