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Adipocyte and Cell Biology

Oxidative and endoplasmic reticulum stress is impaired in leukocytes from metabolically unhealthy vs healthy obese individuals

International Journal of Obesity volume 41, pages 1556–1563 (2017)Cite this article

Subjects

Abstract

Background:

Oxidative stress and inflammation are related to obesity, but the influence of metabolic disturbances on these parameters and their relationship with endoplasmic reticulum (ER) stress is unknown. Therefore, this study was performed to evaluate whether metabolic profile influences ER and oxidative stress in an obese population with/without comorbidities.

Subjects and methods:

A total of 113 obese patients were enrolled in the study; 29 were metabolically healthy (MHO), 53 were metabolically abnormal (MAO) and 31 had type 2 diabetes (MADO). We assessed metabolic parameters, proinflammatory cytokines (TNFα and IL-6), mitochondrial and total reactive oxygen species (ROS) production, glutathione levels, antioxidant enzymes activity, total antioxidant status, mitochondrial membrane potential and ER stress marker expression levels (glucose-regulated protein (GRP78), spliced X-box binding protein 1 (XBP1), P-subunit 1 alpha (P-eIF2α) and activating transcription factor 6 (ATF6).

Results:

The MAO and MADO groups showed higher blood pressure, atherogenic dyslipidemia, insulin resistance and inflammatory profile than that of MHO subjects. Total and mitochondrial ROS production was enhanced in MAO and MADO patients, and mitochondrial membrane potential and catalase activity differed significantly between the MADO and MHO groups. In addition, decreases in glutathione levels and superoxide dismutase activity were observed in the MADO vs MAO and MHO groups. GRP78 and CHOP protein and gene expression were higher in the MAO and MADO groups with respect to MHO subjects, and sXBP1 gene expression was associated with the presence of diabetes. Furthermore, MAO patients exhibited higher levels of ATF6 than their MHO counterparts. Waist circumference was positively correlated with ATF6 and GRP78, and A1c was positively correlated with P-Eif2α. Interestingly, CHOP was positively correlated with TNFα and total ROS production and GRP78 was negatively correlated with glutathione levels.

Conclusions:

Our findings support the hypothesis that both inflammation and oxidative stress are involved in the induction of ER stress signaling pathways in the leukocytes of metabolically unhealthy obese vs healthy obese subjects.

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Acknowledgements

We thank Brian Normanly (University of Valencia/CIBERehd) for his editorial assistance, and Rosa Falcon and Carmen Ramírez (FISABIO) for their technical assistance. This study was financed by grants UGP-15-220 and UGP-15-193 from FISABIO, GV/2016/169 and PROMETEOII2014/035 from the Valencian Regional Ministry of Education and PI16/00301, PI16/01083, PI15/1424 and CIBERehd CB06/04/0071 from Fund for Health Research (FIS) and co-funded by the European Regional Development Fund of the European Union (ERDF A way to build Europe'). SL-D, ND-M are recipients of a predoctoral fellowship and CB is recipient of a Sara Borrell contract (FI14/00350, FI14/00125 and CD14/00043, respectively) from Carlos III Health Institute. S.R-LL. is recipient of a Juan de la Cierva contract from the Spanish Ministry of Economy and Competitiveness (FJCI-2015-25040).VMV and MR are recipients of contracts from the Ministry of Health of the Valencian Regional Government and Carlos III Health Institute (CES10/030 and CPII16/00037, respectively).

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Authors and Affiliations

  1. Service of Endocrinology. University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain

    C Bañuls, S Rovira-Llopis, S Lopez-Domenech, N Diaz-Morales, S Veses, C Morillas, V M Victor, M Rocha & A Hernandez-Mijares

  2. Institute of Health Research INCLIVA, University of Valencia, Valencia, Spain

    C Bañuls, S Rovira-Llopis, S Veses, C Morillas & A Hernandez-Mijares

  3. CIBERehd—Department of Pharmacology and Physiology, University of Valencia, Valencia, Spain

    C Bañuls, A Blas-Garcia, V M Victor & M Rocha

  4. Department of Physiology, University of Valencia, Valencia, Spain

    V M Victor

  5. Department of Medicine, University of Valencia, Valencia, Spain

    A Hernandez-Mijares

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  1. C Bañuls
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Correspondence to C Bañuls, M Rocha or A Hernandez-Mijares.

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Bañuls, C., Rovira-Llopis, S., Lopez-Domenech, S. et al. Oxidative and endoplasmic reticulum stress is impaired in leukocytes from metabolically unhealthy vs healthy obese individuals. Int J Obes 41, 1556–1563 (2017). https://doi.org/10.1038/ijo.2017.147

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