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A lower duodenal immune response is associated with an increase of insulin resistance in patients with morbid obesity

International Journal of Obesity volume 44, pages 340–352 (2020)Cite this article

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Abstract

Objective

The intestinal immune response could play an important role in obesity-related comorbidities. We aim to study the profile of duodenal cytokines and chemokines in patients with morbid obesity (MO), its relation with insulin resistance (IR) and the intake of metformin, and with the evolution of MO after sleeve gastrectomy (SG).

Research design and methods

Duodenal levels of 24 cytokines and 9 chemokines were analyzed in 14 nonobese and in 54 MO who underwent SG: with lower IR (MO-lower-IR), with higher IR (MO-higher-IR), and with type 2 diabetes treated with metformin (MO-metf-T2DM).

Results

MO-lower-IR had higher levels of cytokines related to Th1, Th2, Th9, Th17, Th22, M1 macrophages, and chemokines involved in the recruitment of macrophages and T-lymphocytes (p < 0.05), and total (CD68 expression) and M1 macrophages (ITGAX expression) (p < 0.05) when compared with nonobese patients, but with a decrease in M2 macrophages (MRC1 expression) (p < 0.05). In MO-higher-IR, these chemokines and cytokines decreased and were similar to those found in nonobese patients. In MO-metf-T2DM, only IL-4 (Th2) and IL-22 (Th22) increased their levels with regard to MO-higher-IR (p < 0.05). In MO-higher-IR and MO-metf-T2DM, there was a decrease of CD68 expression (p < 0.05) while ITGAX and MRC1 were similar with regard to MO-lower-IR. We found an association between CXCL8, TNFβ and IL-2 with the evolution of body mass index (BMI) after SG (p < 0.05).

Conclusions

There is an association between a higher IR and a lower duodenal immune response in MO, with a slight increase in those patients with metformin treatment. Intestinal immune response could be involved in the evolution of BMI after SG.

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Acknowledgements

CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and CIBER de Diabetes y Enfermedades Metabólicas (CIBERDEM) are initiatives of ISCIII (Spain). We gratefully acknowledge the Imaging platform of the Institute of Biomedical Research in Malaga (IBIMA) (Spain). This work was supported in part by a grant from the Instituto de Salud Carlos III, Spain (PI12/00338) (“Una manera de hacer Europa”). This study has been co-funded by FEDER funds. AHP is supported by a grant from the Ministerio de Educación y Formación Professional (Spain) (FPU14/01972). CSF is supported by a grant from the ISCIII (Spain) (FI16/00241). LGS is supported by the Miguel Servet program from the ISCIII (Spain) (MS13/00188). CR is supported by a grant from BEIPD-COFUND-OPD, (Belgium) (R.EURO.0992-J-F-B-32). EGF is supported by the Nicolas Monardes program from the Consejería de Salud de Andalucía (Spain) (C-0031-2016).

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Authors and Affiliations

  1. Instituto de Investigación Biomédica de Málaga-IBIMA, Málaga, Spain

    Ailec Ho-Plagaro, Concepción Santiago-Fernandez, Sara García-Serrano, Cristina Rodriguez, Lourdes Garrido-Sanchez, Alejandro Escamilla, Guillermo Alcaín-Martínez & Eduardo Garcia-Fuentes

  2. Unidad de Gesti ón Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Málaga, Spain

    Ailec Ho-Plagaro, Concepción Santiago-Fernandez, Cristina Rodriguez, Guillermo Alcaín-Martínez, Beatriz Garcia-Muñoz, Natalia Ruiz-Santana & Eduardo Garcia-Fuentes

  3. Universidad de Málaga, Málaga, Spain

    Ailec Ho-Plagaro

  4. Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Regional Universitario de Málaga, Málaga, Spain

    Sara García-Serrano & Montserrat Gonzalo

  5. CIBER de Diabetes y Enfermedades Metabólicas Asociadas-CIBERDEM, Málaga, Spain

    Sara García-Serrano

  6. Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Málaga, Spain

    Lourdes Garrido-Sanchez

  7. CIBER Fisiología de la Obesidad y Nutrición-CIBEROBN, Málaga, Spain

    Lourdes Garrido-Sanchez & Eduardo Garcia-Fuentes

  8. Unidad de Gestión Clínica de Cirugía General, Digestiva y Trasplantes, Hospital Regional Universitario de Málaga, Málaga, Spain

    Custodia Montiel-Casado

  9. Unidad de Gestión Clínica de Aparato Digestivo, Hospital Regional Universitario de Málaga, Málaga, Spain

    Luis Vázquez-Pedreño

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  1. Ailec Ho-Plagaro
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Contributions

Conceived and designed the study: EGF. Participated in the selection of patients and samples: EGF, AHP, SGS, MG , CMC, LGS, GAM, BGM, NRS, and LVP. Performed the experiments: AHP, SGS, CSF, AE, and CR. Analyzed the data: AHP, CR, AE, and EGF. Wrote the paper: AHP and EGF. All authors helped to revise the paper and read and approved the final paper. EGF is the guarantor of this paper.

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Correspondence to Lourdes Garrido-Sanchez or Eduardo Garcia-Fuentes.

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Ho-Plagaro, A., Santiago-Fernandez, C., García-Serrano, S. et al. A lower duodenal immune response is associated with an increase of insulin resistance in patients with morbid obesity. Int J Obes 44, 340–352 (2020). https://doi.org/10.1038/s41366-019-0458-1

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