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Integrative Biology

Influence of Roux-en-Y gastric bypass on plasma bile acid profiles: a comparative study between rats, pigs and humans

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Abstract

Background:

Roux-en-Y gastric bypass (RYGBP) is the most widely used bariatric surgery procedure, which induces profound metabolic and physiological effects, such as substantial improvements in obesity, type 2 diabetes and their comorbidities. Increasing evidence identifies bile acids (BAs) as signaling molecules that contribute to the metabolic improvement after RYGBP. However, how and to what extent BAs mediate the metabolic effects of RYGBP still remains unclear and requires mechanism of action studies using preclinical models. In this study, we compared plasma BA profiles before and after RYGBP in two animal models, rats and pigs, with humans to evaluate their translational potential.

Methods:

Plasma BAs were profiled in rats, pigs and humans by liquid chromatography coupled with tandem mass spectrometry before and after RYGBP.

Results:

RYGBP increased baseline plasma total BA concentrations in humans and in the two animal models to a similar extent (∼3-fold increase), despite differences in presurgery BA levels and profiles between the models. However, qualitatively, RYGBP differently affected individual plasma BA species, with similar increases in some free species (cholic acid (CA), chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA)), different increases in glyco-conjugated species depending on the model and globally no increase in tauro-conjugated species whatever the model.

Conclusions:

The tested animal models share similar quantitative RYGBP-induced increases in peripheral blood BAs as humans, which render them useful for mechanistic studies. However, they also present qualitative differences in BA profiles, which may result in different signaling responses. Such differences need to be taken into account when translating results to humans.

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Acknowledgements

We thank C Corteville for technical support in rat surgery. VS was supported by a grant from the Fondation pour la Recherche Médicale (FRM) Grant FDT20140930804. This work was supported by grants from ‘European Genomic Institute for Diabetes’ (EGID, ANR-10-LABX-46), European Commission, Région Nord-Pas de Calais, FEDER, INSERM, A.N.R. (FXREn), Université Lille and Université Lille Nord de France. BS is a member of the Institut Universitaire de France.

Note added in proof

Since submission, it was observed that the free and conjugated UDCA peaks in the LC-MS/MS measurement contain UDCA plus HDCA. The analyzed human and rat samples contain solely HDCA, whereas in pigs HDCA is the major BA in this peak. These findings do not impact the conclusions of the study.

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Author notes

  1. V Spinelli and F Lalloyer: Co-first authors.

  2. B Staels, F Pattou and A Tailleux: Co-last authors.

Authors and Affiliations

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

    V Spinelli, F Lalloyer, E Vallez, S Lestavel, B Staels & A Tailleux

  2. Inserm, U1011, Lille, France

    V Spinelli, F Lalloyer, E Vallez, S Lestavel, B Staels & A Tailleux

  3. CHU Lille, Lille, France

    V Spinelli, F Lalloyer, E Vallez, V Raverdy, S Lestavel, B Staels, F Pattou & A Tailleux

  4. Institut Pasteur de Lille, U1011, Lille, France

    V Spinelli, F Lalloyer, E Vallez, S Lestavel, B Staels & A Tailleux

  5. Université Lille, Inserm, UMR1190, EGID, Lille, France

    G Baud, M Daoudi, V Raverdy, T Hubert & F Pattou

  6. Swiss Federal Institute of Technology, ETH Zürich, Institute of Food Nutrition and Health, Zurich, Switzerland

    E Osto

  7. Department of Cardiology, Center for Molecular Cardiology, University of Zurich and University Heart Center, University Hospital Zurich, Zurich, Switzerland

    E Osto & P Doytcheva

  8. Centre Universitaire de Mesures et d’Analyses, Université Lille, Lille, France

    M Kouach, J-F Goossens & A Descat

  9. Institute of Veterinary Physiology, Vetsuisse Faculty, Center of Integrative Human Physiology, University of Zurich, Zurich, Switzerland

    P Doytcheva & T A Lutz

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  1. V Spinelli
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Correspondence to B Staels.

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Spinelli, V., Lalloyer, F., Baud, G. et al. Influence of Roux-en-Y gastric bypass on plasma bile acid profiles: a comparative study between rats, pigs and humans. Int J Obes 40, 1260–1267 (2016). https://doi.org/10.1038/ijo.2016.46

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