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Bariatric Surgery

Transcriptional and epigenetic changes after dietary and surgical weight loss interventions in an animal model of obesity

International Journal of Obesity volume 48, pages 103–110 (2024)Cite this article

Subjects

Abstract

Background

Identifying determinants that can predict response to weight loss interventions is imperative for optimizing therapeutic benefit. We aimed to identify changes in DNA methylation and mRNA expression of a subset of target genes following dietary and surgical interventions in high-fat-diet (HFD)-induced obese rats.

Methods

Forty-two adult Wistar Han male rats were divided into two groups: control rats (n = 7) and obese rats (n = 28), fed a HFD for 10 weeks (t10). Obese rats were randomly subdivided into five intervention groups (seven animals per group): (i) HFD; (ii) very-low-calorie diet (VLCD); (iii) sham surgery, and (iv) sleeve gastrectomy (SG). At week sixteen (t16), animals were sacrificed and tissue samples were collected to analyze changes in DNA methylation and mRNA expression of the selected genes.

Results

By type of intervention, the surgical procedures led to the greatest weight loss. Changes in methylation and/or expression of candidate genes occurred proportionally to the effectiveness of the weight loss interventions. Leptin expression, increased sixfold in the visceral fat of the obese rats, was partially normalized after all interventions. The expression of fatty acid synthase (FASN) and monocyte chemoattractant protein 1 (MCP-1) genes, which was reduced 0.5- and 0.15-fold, respectively, in the liver tissue of obese rats, were completely normalized after weight loss interventions, particularly after surgical interventions. The upregulation of FASN and MCP-1 gene expression was accompanied by a significant reduction in promoter methylation, up to 0.5-fold decrease in the case of the FASN (all intervention groups) and a 0.8-fold decrease in the case of the MCP-1 (SG group).

Conclusions

Changes in tissue expression of specific genes involved in the pathophysiological mechanisms of obesity can be significantly attenuated following weight loss interventions, particularly surgery. Some of these genes are regulated by epigenetic mechanisms.

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Fig. 1: Schematic diagram of the experimental design.
Fig. 2: Weight evolution in the experimental groups from week 10 to week 16.

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Data availability

The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors received medical writing support from Luis Francisco García-Fernández, Ph.D. The study was funded by Instituto de Salud Carlos III, Spain (Grant no. PI12/00448).

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Authors and Affiliations

  1. Department of General and Digestive Surgery, Germans Trias i Pujol University Hospital, Badalona, Barcelona, Spain

    Manel Cremades, Jordi Tarascó, Pau Moreno, Albert Caballero & José M. Balibrea

  2. Universitat Autònoma de Barcelona, Barcelona, Spain

    Manel Cremades, Jordi Tarascó, Pau Moreno, Silvia Pellitero & José M. Balibrea

  3. Esophagogastric and Bariatric Surgery Unit, Department of General and Digestive Surgery, Donostia University Hospital, Donostia, Guipuzkoa, Spain

    Eider Talavera-Urquijo

  4. Bariatric and Upper Gastrointestinal Surgery Unit, Department of General and Digestive Surgery, Hospital del Mar, Barcelona, Spain

    Marc Beisani

  5. Universitat Pompeu Fabra, Barcelona, Spain

    Marc Beisani

  6. Germans Trias i Pujol Research Institute (IGTP), Badalona, Barcelona, Spain

    Stella Pappa & Mireia Jordà

  7. Endocrine-Metabolic and Bariatric Surgery Unit, Germans Trias i Pujol University Hospital, Badalona, Barcelona, Spain

    Jordi Tarascó, Pau Moreno, Albert Caballero & José M. Balibrea

  8. Department of Endocrinology, Nutrition and Metabolism, Germans Trias i Pujol University Hospital, Badalona, Barcelona, Spain

    Eva Martínez-López & Silvia Pellitero

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  1. Manel Cremades
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Contributions

Study design: JMB, MC, and ET. Execution of the experimental model and sampling: MC, ET, and MB. Biomolecular studies: MJ. Analysis and interpretation of results: SP, JT, PM, and AC. Writing of the preliminary draft: MC and JMB. Critical revision of the manuscript: JMB, SP, and PM. All authors read and approved the final manuscript.

Corresponding author

Correspondence to José M. Balibrea.

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Cremades, M., Talavera-Urquijo, E., Beisani, M. et al. Transcriptional and epigenetic changes after dietary and surgical weight loss interventions in an animal model of obesity. Int J Obes 48, 103–110 (2024). https://doi.org/10.1038/s41366-023-01395-1

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