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

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

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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. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution


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DISEASES Article Open access 09 June 2020 IN SEVERE OBESITY, SUBCUTANEOUS ADIPOSE TISSUE CELL-DERIVED CYTOKINES ARE EARLY MARKERS OF IMPAIRED GLUCOSE TOLERANCE AND ARE MODULATED BY QUERCETIN


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to the travelers. Cytokine Growth Factor Rev. 2014;25:83–89. Article  CAS  Google Scholar  Download references 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). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * 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 * 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 * Universidad de Málaga, Málaga, Spain Ailec Ho-Plagaro * Unidad de Gestión


Clínica de Endocrinología y Nutrición, Hospital Regional Universitario de Málaga, Málaga, Spain Sara García-Serrano & Montserrat Gonzalo * CIBER de Diabetes y Enfermedades Metabólicas


Asociadas-CIBERDEM, Málaga, Spain Sara García-Serrano * Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Málaga, Spain Lourdes


Garrido-Sanchez * CIBER Fisiología de la Obesidad y Nutrición-CIBEROBN, Málaga, Spain Lourdes Garrido-Sanchez & Eduardo Garcia-Fuentes * Unidad de Gestión Clínica de Cirugía General,


Digestiva y Trasplantes, Hospital Regional Universitario de Málaga, Málaga, Spain Custodia Montiel-Casado * Unidad de Gestión Clínica de Aparato Digestivo, Hospital Regional Universitario de


Málaga, Málaga, Spain Luis Vázquez-Pedreño Authors * Ailec Ho-Plagaro View author publications You can also search for this author inPubMed Google Scholar * Concepción Santiago-Fernandez


View author publications You can also search for this author inPubMed Google Scholar * Sara García-Serrano View author publications You can also search for this author inPubMed Google


Scholar * Cristina Rodriguez View author publications You can also search for this author inPubMed Google Scholar * Lourdes Garrido-Sanchez View author publications You can also search for


this author inPubMed Google Scholar * Alejandro Escamilla View author publications You can also search for this author inPubMed Google Scholar * Montserrat Gonzalo View author publications


You can also search for this author inPubMed Google Scholar * Custodia Montiel-Casado View author publications You can also search for this author inPubMed Google Scholar * Guillermo


Alcaín-Martínez View author publications You can also search for this author inPubMed Google Scholar * Beatriz Garcia-Muñoz View author publications You can also search for this author


inPubMed Google Scholar * Natalia Ruiz-Santana View author publications You can also search for this author inPubMed Google Scholar * Luis Vázquez-Pedreño View author publications You can


also search for this author inPubMed Google Scholar * Eduardo Garcia-Fuentes View author publications You can also search for this author inPubMed Google Scholar 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.


CORRESPONDING AUTHORS Correspondence to Lourdes Garrido-Sanchez or Eduardo Garcia-Fuentes. ETHICS DECLARATIONS CONFLICT OF INTEREST The authors declare that they have no conflict of


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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 Download citation * Received: 18 December 2018 * Revised: 19 July 2019 * Accepted: 28 July 2019 * Published: 25


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