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Bariatric Surgery

The anorexigenic peptide neurotensin relates to insulin sensitivity in obese patients after BPD or RYGB metabolic surgery

International Journal of Obesity volume 42, pages 2057–2061 (2018)Cite this article

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Abstract

Neurotensin is a peptide with effects on appetite and intestinal lipid absorption. Experimental data suggest a role in glucose homeostasis, while human data is missing. Here, 20 morbidly obese subjects either underwent biliopancreatic diversion with duodenal switch (BPD), or Roux-en-Y gastric bypass (RYGB) in a randomized fashion. Before and 1 year after surgery, anthropometric data, body composition, clinical biochemistry, insulin sensitivity by means of euglycemic hyperinsulinemic clamps (HEC) and fasting plasma proneurotensin 1–117 were analyzed. Plasma proneurotensin increased significantly more 1 year after BDP than RYGB (P = 0.028), while weight loss was comparable. After metabolic surgery, proneurotensin correlated positively with insulin sensitivity (M-value) (r = 0.55, P < 0.001), while an inverse relationship with fasting glucose, HOMA-IR and HbA1c was observed (P < 0.05 for all components). After adjustment for age and gender, proneurotensin and BMI remained independently related with delta of M-value (β = 0.46 and β = 0.51, P < 0.05, resp.). From these data we conclude that proneurotensin positively correlates with insulin sensitivity uniquely after weight loss induced by metabolic surgery in humans. BDP leads to a stronger increase in the anorexigenic peptide compared to RYGB.

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References

  1. Mingrone G, Panunzi S, De Gaetano A, Guidone C, Iaconelli A, Nanni G, et al. Bariatric-metabolic surgery versus conventional medical treatment in obese patients with type 2 diabetes: 5 year follow-up of an open-label, single-centre, randomised controlled trial. Lancet. 2015;386:964–73.

    Article  Google Scholar 

  2. Raffaelli M, Iaconelli A, Nanni G, Guidone C, Callari C, Fernandez Real JM, et al. Effects of biliopancreatic diversion on diurnal leptin, insulin and free fatty acid levels. Br J Surg. 2015;102:682–90.

    Article  CAS  Google Scholar 

  3. Armstrong MJ, Parker MC, Ferris CF, Leeman SE. Neurotensin stimulates [3H]oleic acid translocation across rat small intestine. Am J Physiol. 1986;251(6 Pt 1):G823–29.

    CAS  PubMed  Google Scholar 

  4. Li J, Song J, Zaytseva YY, Liu Y, Rychahou P, Jiang K, et al. An obligatory role for neurotensin in high-fat-diet-induced obesity. Nature. 2016;533:411–5.

    Article  CAS  Google Scholar 

  5. Melander O, Maisel AS, Almgren P, Manjer J, Belting M, Hedblad B, et al. Plasma proneurotensin and incidence of diabetes, cardiovascular disease, breast cancer, and mortality. JAMA. 2012;308:1469–75.

    Article  CAS  Google Scholar 

  6. Ratner C, Skov LJ, Raida Z, Bächler T, Bellmann-Sickert K, Le Foll C, et al. Effects of Peripheral Neurotensin on Appetite Regulation and Its Role in Gastric Bypass Surgery. Endocrinology. 2016;157:3482–92.

    Article  CAS  Google Scholar 

  7. Holdstock C, Zethelius B, Sundbom M, Karlsson FA, Edén Engström B. Postprandial changes in gut regulatory peptides in gastric bypass patients. Int J Obes (Lond). 2008;32:1640–6.

    Article  CAS  Google Scholar 

  8. Christ-Crain M, Stoeckli R, Ernst A, Morgenthaler NG, Bilz S, Korbonits M, Struck J, Bergmann A, Müller B, Keller U. Effect of gastric bypass and gastric banding on proneurotensin levels in morbidly obese patients. J Clin Endocrinol Metab. 2006;91:3544–7.

    Article  CAS  Google Scholar 

  9. Ernst A, Hellmich S, Bergmann A. Proneurotensin 1-117, a stable neurotensin precursor fragment identified in human circulation. Peptides. 2006;27:1787–93.

    Article  CAS  Google Scholar 

  10. Januzzi JL Jr, Lyass A, Liu Y, Gaggin H, Trebnick A, Maisel AS, et al. Circulating proneurotensin concentrations and cardiovascular disease events in the community: the Framingham Heart Study. Arterioscler Thromb Vasc Biol. 2016;36:1692–7.

    Article  CAS  Google Scholar 

  11. Tewari N, Awad S, Macdonald IA, Lobo DN. Obesity-related insulin resistance: implications for the surgical patient. Int J Obes (Lond). 2015;39:1575–88.

    Article  CAS  Google Scholar 

  12. Basso N, Soricelli E, Castagneto-Gissey L, Casella G, Albanese D, Fava F, et al. Insulin resistance, microbiota and fat distribution changes by a new model of vertical sleeve gastrectomy in obese rats. Diabetes. 2016;65:2990–3001.

    Article  CAS  Google Scholar 

  13. Hanefeld M, Pistrosch F, Bornstein SR, Birkenfeld AL. The metabolic vascular syndrome - guide to an individualized treatment. Rev Endocr Metab Disord. 2016;17:5–17.

    Article  CAS  Google Scholar 

  14. Kumashiro N, Erion DM, Zhang D, Kahn M, Beddow SA, Chu X, et al. Cellular mechanism of insulin resistance in nonalcoholic fatty liver disease. Proc Natl Acad Sci U S A. 2016;108:16381–5.

    Article  Google Scholar 

  15. Shigiyama F, Kumashiro N, Furukawa Y, Funayama T, Takeno K, Wakui N, et al. Characteristics of hepatic insulin-sensitive nonalcoholic fatty liver disease. Hepatol Commun. 2017;1:634–47.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Julia Paditz and Stephan Friebe for excellent technical assistance. This work was funded by grant from the German Research Foundation (DFG) to ALB, GM, AK, SRB (IRTG 2251).

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    Authors and Affiliations

    1. Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany

      Christian von Loeffelholz

    2. Department of Anaesthesiology and Intensive Care, Jena University Hospital, Jena, Germany

      Christian von Loeffelholz

    3. Department of Surgery, Sapienza University of Rome, Rome, Italy

      Lidia Castagneto Gissey & Giovanni Casella

    4. Section of Metabolic and Vascular Medicine, Medical Clinic III, University Hospital Carl Gustav Carus, Dresden, Germany

      Tina Schumann, Christine Henke, Anica Kurzbach, Markolf Hanefeld, Ulrike Schatz, Stefan R. Bornstein & Andreas L. Birkenfeld

    5. Sphingotec GmbH, Hennigsdorf, Germany

      Joachim Struck & Andreas Bergmann

    6. Study Center for Metabolic Vascular Medicine, GWT-TU Dresden GmbH, Dresden, Germany

      Markolf Hanefeld & Andreas L. Birkenfeld

    7. Department of Internal Medicine, Catholic University of the Sacred Heart, Rome, Italy

      Stefan R. Bornstein & Geltrude Mingrone

    8. Diabetes and Nutritional Sciences, King’s College London, London, UK

      Stefan R. Bornstein, Geltrude Mingrone & Andreas L. Birkenfeld

    9. Paul Langerhans Institute Dresden of the Helmholtz Center Munich at University Hospital and Faculty of Medicine, TU Dresden, Dresden, Germany

      Stefan R. Bornstein & Andreas L. Birkenfeld

    10. German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany

      Stefan R. Bornstein & Andreas L. Birkenfeld

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    1. Christian von Loeffelholz
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    Corresponding authors

    Correspondence to Christian von Loeffelholz or Andreas L. Birkenfeld.

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    Conflict of interest

    JS is employed by sphingotec GmbH, a company having patent rights in the proneurotensin assay and commercializing it. AB is CEO of sphingotec GmbH and holds shares in this company. The remaining authors declare that they have no conflict of interest.

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    These authors contributed equally: Christian von Loeffelholz, Lidia Castagneto Gissey.

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    von Loeffelholz, C., Gissey, L.C., Schumann, T. et al. The anorexigenic peptide neurotensin relates to insulin sensitivity in obese patients after BPD or RYGB metabolic surgery. Int J Obes 42, 2057–2061 (2018). https://doi.org/10.1038/s41366-018-0084-3

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    • DOI: https://doi.org/10.1038/s41366-018-0084-3

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