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Clinical Research

Weight loss normalizes enhanced expression of the oncogene survivin in visceral adipose tissue and blood leukocytes from individuals with obesity

International Journal of Obesity volume 45, pages 206–216 (2021)Cite this article

Subjects

Abstract

Background/objectives

Survivin is an oncogene associated with a decrease in apoptosis, an increase in tumor growth, and poor clinical outcome of diverse malignancies. A correlation between obesity, cancer, and survivin is reported in the literature. To date, the impact of weight loss on change in survivin levels is understudied. This study was aimed at: (1) comparing survivin levels in adipose tissue (AT) from lean and obese animal models and evaluating changes after weight loss induced by energy restriction and/or exercise; (2) comparing survivin levels in normal weighted and obese humans and evaluating changes in survivin levels after weight loss induced by a very-low-calorie ketogenic diet (VLCKD) or bariatric surgery in AT and/or blood leukocytes (PBL/PBMCs).

Subjects/methods

Survivin expression was evaluated in subcutaneous (SAT) and visceral (VAT) AT derived from animal models of monogenic (Zucker rats) and diet-induced obesity (Sprague Dawley rats and C57BL/6J mice) and after a 4-week weight-loss protocol of energy restriction and/or exercise. Plasma was used to measure the inflammatory status. Survivin expression was also evaluated in PBMCs from patients with obesity and compared with normal weight, in PBLs after VLCKD, and in SAT and/or PBLs after bariatric surgery.

Results

Survivin expression was specifically higher in VAT from obese that lean animals, without differences in SAT. It decreased after weight loss induced by energy restriction and correlated with adiposity and inflammatory markers. In humans, the correlation between being obese and higher levels of survivin was confirmed. In obese subjects, survivin levels were reduced following weight loss after either VLCKD or bariatric surgery. Particularly, a decrease in PBMCs expression (not in SAT one) was found after surgery.

Conclusions

Weight loss is effective in decreasing survivin levels. Also, PBL/PBMC should be regarded as appropriate mirror of survivin levels in VAT for the identification of an obesity-related protumoral microenvironment.

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Fig. 1: Survivin expression (gene and protein) in AT from obese Zucker rats after weight-loss intervention.
Fig. 2: Survivin gene expression in humans related with adiposity grade.

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Acknowledgements

The authors thank Maribel Rendo and Maria Amil from the Department of Molecular and Cellular Endocrinology of the Instituto de Investigacion Sanitaria de Santiago (IDIS) for their support with research data management. This study was supported by the Centro de Investigacion Biomedica en Red de Fisiopatologia de la Obesidad y Nutricion (CIBERobn) and grants from the Instituto de Salud Carlos III-ISCIII (PI17/01287), and it was cofinanced by the European Regional Development Fund (FEDER). ABC is funded by a research contract “Miguel Servet” (CP17/00088) from the ISCIII and cofinanced by the European Regional Development Fund (FEDER).

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Author notes

  1. These authors contributed equally: Andrea G. Izquierdo, Marcos C. Carreira

Authors and Affiliations

  1. Epigenomics in Endocrinology and Nutrition Group, Instituto de Investigacion Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, Spain

    Andrea G. Izquierdo, Gemma Rodriguez-Carnero, Miguel A. Martinez-Olmos & Ana B. Crujeiras

  2. CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Madrid, Spain

    Andrea G. Izquierdo, Marcos C. Carreira, Alfredo Fernandez-Quintela, Miguel A. Martinez-Olmos, Francisco J. Ortega, Maria P. Portillo, Jose M. Fernandez-Real, Felipe F. Casanueva & Ana B. Crujeiras

  3. Molecular Endocrinology Group, Instituto de Investigacion Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain

    Marcos C. Carreira, Aurelio M. Sueiro & Felipe F. Casanueva

  4. Nutrition and Obesity Group, Department of Nutrition and Food Science, University of the Basque Country (UPV/EHU) and Lucio Lascaray Research Institute, Vitoria, Spain

    Alfredo Fernandez-Quintela & Maria P. Portillo

  5. Medical Department Pronokal, Pronokal Group, Barcelona, Spain

    German Guzman

  6. Endocrinology and Nutrition Research Center, School of Medicine, Department of Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid, Spain

    Daniel De Luis

  7. Department of Internal Medicine, Laboratory of Nutrigenomic Studies, Ribeirao Preto Medical School, FMRP, University of Sao Paulo, USP, Sao Paulo, Brazil

    Marcela A. S. Pinhel, Carolina F. Nicoletti & Carla B. Nonino

  8. Department of Diabetes, Endocrinology, and Nutrition (UDEN), Institut d’Investigació Biomèdica de Girona (IdIBGi), Girona, Spain

    Francisco J. Ortega & Jose M. Fernandez-Real

Authors
  1. Andrea G. Izquierdo
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  2. Marcos C. Carreira
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  3. Gemma Rodriguez-Carnero
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  4. Alfredo Fernandez-Quintela
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  6. Miguel A. Martinez-Olmos
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  15. Felipe F. Casanueva
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  16. Ana B. Crujeiras
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Contributions

AGI and ABC designed the study. AGI, MCC, AFQ, and MPP contributed to the acquisition of the data and samples from the animal models. GRC, MAMO, and AMS contributed to the acquisition of the data and samples from human. GG and DDL performed the nutrition intervention to lose weight. FJO, JMFR, CFN, CBN, and MASP contributed to the acquisition of the data and samples from the bariatric surgery cohort. AGI and ABC performed the statistical analysis. AGI, MCC, and ABC wrote the first draft of the paper, and FFC contributed to the interpretation of data and critical revision of the paper. All authors were involved in the writing of the paper and approved the final version of this article.

Corresponding author

Correspondence to Ana B. Crujeiras.

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Conflict of interest

ABC, FFC, and DDL received research grants and conference fees from Pronokal Spain. GG is medical director of Pronokal Group. The other authors declare no conflict of interest regarding the results of this study.

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Izquierdo, A.G., Carreira, M.C., Rodriguez-Carnero, G. et al. Weight loss normalizes enhanced expression of the oncogene survivin in visceral adipose tissue and blood leukocytes from individuals with obesity. Int J Obes 45, 206–216 (2021). https://doi.org/10.1038/s41366-020-0630-7

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