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Roux-en-Y gastric bypass increases systemic but not portal bile acid concentrations by decreasing hepatic bile acid uptake in minipigs

International Journal of Obesity volume 41, pages 664668 (2017) | Download Citation

Abstract

Roux-en-Y gastric bypass (RYGB) surgery is widely used in the management of morbid obesity. RYGB improves metabolism independently of weight loss by still unknown mechanisms. Bile acids (BAs) are good candidates to explain this benefit, since they regulate metabolic homeostasis and their systemic concentrations increase upon RYGB. Here we analyzed the mechanisms underlying the increase in systemic BA concentrations after RYGB and the role of the liver therein. To this aim, we used the Göttingen-like minipig, a human-size mammalian model, which allows continuous sampling and simultaneous analysis of pre-hepatic portal and systemic venous blood. BA concentrations and pool composition were measured in portal blood, containing intestinal reabsorbed BAs and compared to systemic blood during a standardized meal test before and after RYGB. Systemic total BA concentrations increased after RYGB, due to an increase in conjugated BAs. Interestingly, the ratio of portal:systemic conjugated BAs decreased after RYGB, indicating a role for the liver in systemic BA concentrations changes. In line, hepatic expression of BA transporter genes decreased after RYGB. Our results show that the increase in systemic BAs after surgery is due to decreased selective hepatic recapture. Thus, alterations in hepatic function contribute to the increase in systemic BAs after RYGB.

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Acknowledgements

We thank Audray Quenon, Amandine Descat, Bruno Derudas, Arnold Dive, Michel Pottier and Mathieu Fourdrinier for excellent technical assistance. VS was supported by a grant from the Fondation pour la Recherche Médicale (FRM) Grant FDT20140930804. This work was supported by Grants from Région Nord-Pas de Calais, FEDER, INSERM, ANR (FXREn), Société Francophone du Diabète (SFD), Institut Universitaire de France and European Genomic Institute for Diabetes (EGID, ANR-10-LABX-46), and European Commission.

Author information

Author notes

    • O Chávez-Talavera
    • , G Baud
    •  & V Spinelli

    Co-first authors.

    • A Tailleux
    • , B Staels
    •  & F Pattou

    Co-last authors.

Affiliations

  1. Université de Lille, U1011 - EGID, Lille, France

    • O Chávez-Talavera
    • , V Spinelli
    • , E Vallez
    • , S Lestavel
    • , A Tailleux
    •  & B Staels
  2. Inserm, U1011, Lille, France

    • O Chávez-Talavera
    • , V Spinelli
    • , E Vallez
    • , S Lestavel
    • , A Tailleux
    •  & B Staels
  3. CHU Lille, Lille, France

    • O Chávez-Talavera
    • , G Baud
    • , V Spinelli
    • , M Daoudi
    • , E Vallez
    • , R Caiazzo
    • , M Ghunaim
    • , T Hubert
    • , S Lestavel
    • , A Tailleux
    • , B Staels
    •  & F Pattou
  4. Institut Pasteur de Lille, Lille, France

    • O Chávez-Talavera
    • , V Spinelli
    • , E Vallez
    • , S Lestavel
    • , A Tailleux
    •  & B Staels
  5. PECEM, Faculty of Medicine, UNAM, Mexico City, Mexico

    • O Chávez-Talavera
  6. Université de Lille, U1190-EGID, Lille, France

    • G Baud
    • , M Daoudi
    • , R Caiazzo
    • , M Ghunaim
    • , T Hubert
    •  & F Pattou
  7. Inserm, U1190, Lille, France

    • G Baud
    • , M Daoudi
    • , R Caiazzo
    • , M Ghunaim
    • , T Hubert
    •  & F Pattou
  8. Centre Universitaire de Mesures et d’Analyses, Université de Lille, Lille France

    • M Kouach
    •  & J-F Goossens

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Competing interests

The authors declare no conflict of interest.

Corresponding author

Correspondence to B Staels.

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DOI

https://doi.org/10.1038/ijo.2017.7

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