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Six-transmembrane epithelial antigen of prostate 4 and neutrophil gelatinase-associated lipocalin expression in visceral adipose tissue is related to iron status and inflammation in human obesity

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Abstract

Purpose

Six-transmembrane epithelial antigen of prostate (STEAP)-4 and neutrophil gelatinase-associated lipocalin (NGAL) are novel adipokines related to iron homeostasis with potential roles in insulin resistance and inflammation. The aim of the present work was to evaluate the effect of obesity and iron status on gene expression levels of STEAP-4 and NGAL in visceral adipose tissue (VAT) and its implication in inflammation.

Methods

VAT biopsies obtained from 53 subjects were used in the study. Real-time PCR and Western-blot were performed to quantify the levels of STEAP4 and NGAL in VAT as well as the association with other genes implicated in inflammatory pathways. Circulating ferritin and free iron concentrations were also determined.

Results

Obese patients exhibited significantly increased STEAP4 and NGAL mRNA expression levels (P < 0.001) compared to lean subjects. Protein expression levels of NGAL (P < 0.05) and STEAP4 were also higher in the visceral fat depot of obese patients, although protein levels of STEAP4 did not reach statistical significance. A negative correlation (P < 0.05) between free iron concentrations and gene expression levels of both STEAP4 and NGAL was found, while circulating ferritin concentrations were positively correlated (P < 0.05) with NGAL mRNA after body fat (BF) adjustment. Furthermore, a significant positive association between STEAP4 and NGAL gene expression levels with inflammatory markers was also detected (P < 0.01).

Conclusion

These findings represent the first observation that STEAP4 and NGAL mRNA and protein levels in human VAT are related to iron status. Moreover, STEAP4 and NGAL are associated with pro-inflammatory markers suggesting their potential involvement in the low-grade chronic inflammation accompanying obesity.

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Acknowledgments

This work was supported by Fondo de Investigacion Sanitaria (FIS) PI09/02330, PI08/1146, PI11/02681 from the Spanish Instituto de Salud Carlos III, by the Department of Health (48/2011 and 58/2011) of the Gobierno de Navarra of Spain and by Plan de Investigacion de la Universidad de Navarra (PIUNA) (2009–2011).

The authors gratefully acknowledge the valuable collaboration of all the members of the Multidisciplinary Obesity Team, Clínica Universidad de Navarra, Pamplona, Spain. CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN) is an initiative of the Instituto de Salud Carlos III, Spain.

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Authors and Affiliations

  1. Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain

    Victoria Catalán, Javier Gómez-Ambrosi, Amaia Rodríguez, Beatriz Ramírez & Gema Frühbeck

  2. Department of Surgery, Clínica Universidad de Navarra, Pamplona, Spain

    Fernando Rotellar & Victor Valentí

  3. Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, Avda. Pío XII 36, 31008, Pamplona, Spain

    Camilo Silva, Javier Salvador & Gema Frühbeck

  4. Department of Biochemistry, Clínica Universidad de Navarra, Pamplona, Spain

    María J. Gil

  5. CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 31008, Pamplona, Spain

    Victoria Catalán, Javier Gómez-Ambrosi, Amaia Rodríguez, Beatriz Ramírez, Fernando Rotellar, Victor Valentí, Camilo Silva, María J. Gil, Javier Salvador & Gema Frühbeck

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  1. Victoria Catalán
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Correspondence to Victoria Catalán.

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Catalán, V., Gómez-Ambrosi, J., Rodríguez, A. et al. Six-transmembrane epithelial antigen of prostate 4 and neutrophil gelatinase-associated lipocalin expression in visceral adipose tissue is related to iron status and inflammation in human obesity. Eur J Nutr 52, 1587–1595 (2013). https://doi.org/10.1007/s00394-012-0464-8

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