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Bariatric Surgery

Body weight-dependent and independent improvement in lipid metabolism after Roux-en-Y gastric bypass in ApoE*3Leiden.CETP mice

International Journal of Obesity volume 43, pages 2394–2406 (2019)Cite this article

Subjects

Abstract

Background/Objectives

The incidence of obesity and metabolic syndrome (MetS) has rapidly increased worldwide. Roux-en-Y gastric bypass (RYGB) achieves long-term weight loss and improves MetS-associated comorbidities. Using a mouse model with a humanized lipoprotein metabolism, we elucidated whether improvements in lipid and glucose metabolism after RYGB surgery are body weight loss-dependent or not.

Subjects/Methods

Male ApoE*3Leiden.CETP (ApoE3L.CETP) mice fed Western type diet for 6 weeks underwent RYGB or Sham surgery. Sham groups were either fed ad libitum or were body weight-matched (BWm) to the RYGB mice to discriminate surgical effects from body weight loss-associated effects. Before and after surgery, plasma was collected to assess the metabolic profile, and glucose tolerance and insulin sensitivity were tested. Twenty days after surgery, mice were sacrificed, and liver was collected to assess metabolic, histological and global gene expression changes after surgery.

Results

RYGB induced a marked reduction in body weight, which was also achieved by severe food restriction in BWm mice, and total fat mass compared to Sham ad libitum mice (Sham AL). Total cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C) and ceramide were strongly reduced 20 days after surgery in RYGB compared to BWm mice. Glucose tolerance and insulin sensitivity improved 13 days after surgery similarly in RYGB and BWm mice. Liver histology confirmed lipid reduction in RYGB and BWm mice while the transcriptomics data indicated altered genes expression in lipid metabolism.

Conclusions

RYGB surgery improves glucose metabolism and greatly ameliorates lipid metabolism in part in a body weight-dependent manner. Given that ApoE3L.CETP mice were extensively studied to describe the MetS, and given that RYGB improved ceramide after surgery, our data confirmed the usefulness of ApoE3L.CETP mice after RYGB in deciphering the metabolic improvements to treat the MetS.

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Acknowledgements

We are grateful to Prof. Arnold von Eckardstein from the Institute of Clinical Chemistry of the University of Zurich for his fruitful and expert discussions. We also thank RESOLVE EU-FP7 for generous funding and the Center for Clinical Studies (Vetsuisse Faculty) for kindly letting us use their equipment. We also thank Christelle le Foll for a critical revision of the manuscript.

Funding

This work was supported in part by the European Union (RESOLVE, FP7-HEALTH 305707; TAL and TH) and by the University of Zurich Forschungskredit (FK-17-061; ET).

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Author notes

  1. Giovanni Pellegrini

    Present address: Drug Safety and Metabolism, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden

Authors and Affiliations

  1. Institute of Veterinary Physiology, Vetsuisse Faculty University of Zurich, Zurich, Switzerland

    Erika Tarasco, Christina N. Boyle & Thomas A. Lutz

  2. Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland

    Erika Tarasco, Thorsten Hornemann & Thomas A. Lutz

  3. Laboratory for Animal Model Pathology (LAMP), Institute of Veterinary Pathology, Vetsuisse Faculty University of Zurich, Zurich, Switzerland

    Giovanni Pellegrini

  4. Physiology and Behaviour Laboratory, ETH Zurich, Schwerzenbach, Switzerland

    Myrtha Arnold

  5. Institute of Clinical Chemistry, University and University Hospital of Zurich, Zurich, Switzerland

    Regula Steiner & Thorsten Hornemann

  6. Department of Basic Medical Sciences, University of Crete Medical School and Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology of Hellas, Crete, Greece

    Dimitris Nasias & Dimitris Kardassis

  7. Institute of “Drug and Discovery Biology”, University of Monash, VIC, Australia

    Lynda Whiting

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Tarasco, E., Boyle, C.N., Pellegrini, G. et al. Body weight-dependent and independent improvement in lipid metabolism after Roux-en-Y gastric bypass in ApoE*3Leiden.CETP mice. Int J Obes 43, 2394–2406 (2019). https://doi.org/10.1038/s41366-019-0408-y

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