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Molecular Biology

Dietary weight loss intervention improves subclinical atherosclerosis and oxidative stress markers in leukocytes of obese humans

International Journal of Obesity (2019) | Download Citation



The relationship between caloric restriction-mediated weight loss and the generation of ROS and its effects on atherosclerotic markers in obesity is not fully understood. Therefore, we set out to investigate whether dietary weight loss intervention improves markers of oxidative stress in leukocytes and subclinical parameters of atherosclerosis.

Subjects and Methods

This was an interventional study of 59 obese subjects (BMI > 35 kg/m2) who underwent 6 months of dietary therapy, including a 6-week very-low-calorie diet (VLCD) followed by an 18-week low-calorie diet (LCD). We determined clinical parameters, inflammatory markers—hsCRP, TNFα and NFκB –, oxidative stress parameters—total superoxide, glutathione, catalase activity and protein carbonyl groups–, soluble cellular adhesion molecules—sICAM, sP-selectin, sPSGL-1 –, myeloperoxidase (MPO), leukocyte-endothelium cell interactions—rolling flux, velocity and adhesion—and LDL subfractions, before and after the dietary intervention.


After losing weight, an improvement was observed in the patients’ anthropometric, blood pressure and metabolic parameters, and was associated with reduced inflammatory response (hsCRP, TNFα and NFκB). Oxidative stress parameters improved, since superoxide production and protein carbonyl content were reduced and antioxidant systems were enhanced. In addition, a significant reduction of subclinical markers of atherosclerosis—small and dense LDL particles, MPO, sP-selectin and leukocyte adhesion—and an increase in soluble PSGL-1 were reported.


Our findings reveal that the improvement of subclinical atherosclerotic markers after dietary weight loss intervention is associated with a reduction of oxidative stress in leukocytes and inflammatory pathways, suggesting that these are the underlying mechanisms responsible for the reduced risk of cardiovascular disease in obese subjects after losing weight.

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We acknowledge the editorial assistance of Brian Normanly (CIBERehd). This study was supported by grant PI16/00301 and PI16/01083 from Carlos III Health Institute and has been co-funded by the European Regional Development Fund (ERDF “A way to build Europe”) and UGP-15–220 from FISABIO. Unrestricted grant from Menarini S.A. MM-H is a predoctoral fellowship from Valencian Regional Ministry of Education (ACIF/2015/226), SL-D, ND-M and ZA-J are recipients of a predoctoral fellowship and from Carlos III Health Institute (FI14/00350, FI14/00125 and FI17/00144, respectively). IE-L has a predoctoral fellowship from FISABIO (UGP-15–144). MR is recipient of Miguel Servet (CPII16/0037) contract from Carlos III Health Institute.

Author contribution

The authors’ responsibilities were as follows. MR and VM-V contributed to the conception and design of the study. CB assisted in the design of the experiments and provided support throughout the course of the study. CM, SL-D and MM-H carried out the recruitment, diagnosis and follow-up of the patients in the study. SL-D, MM-H, ZA-J, IE-L and ND-M performed the laboratory analyses and collected data. SL-D, MM-H and MR analyzed the data, performed the statistical analysis and drafted the manuscript. MR, and VM-V critically revised the manuscript and were responsible for its final content. All authors read and approved the final version of the manuscript.

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Author notes

  1. These authors contributed equally: Sandra López-Domènech, Mayte Martínez-Herrera


  1. Service of Endocrinology and Nutrition, University Hospital Doctor Peset-FISABIO, Av. Gaspar Aguilar 90, 46017, Valencia, Spain

    • Sandra López-Domènech
    • , Zaida Abad-Jiménez
    • , Carlos Morillas
    • , Irene Escribano-López
    • , Noelia Díaz-Morales
    • , Celia Bañuls
    • , Víctor M. Víctor
    •  & Milagros Rocha
  2. Service of Stomatology, University Hospital Doctor Peset-FISABIO, Av. Gaspar Aguilar 90, 46017, Valencia, Spain

    • Mayte Martínez-Herrera
  3. CIBER CB06/04/0071 Research Group. CIBER Hepatic and Digestive Diseases, University of Valencia, Av Blasco Ibáñez 13, 46010, Valencia, Spain

    • Víctor M. Víctor
    •  & Milagros Rocha
  4. Department of Physiology, University of Valencia, Av. Blasco Ibáñez 13, 46010, Valencia, Spain

    • Víctor M. Víctor


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The authors declare that they have no conflict of interest.

Corresponding authors

Correspondence to Víctor M. Víctor or Milagros Rocha.

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