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Increased adipose tissue expression of lipocalin-2 in obesity is related to inflammation and matrix metalloproteinase-2 and metalloproteinase-9 activities in humans

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Abstract

Lipocalin-2 (LCN2) is a novel adipokine with potential roles in obesity, insulin resistance, and inflammation. The aim of the present work was to evaluate the effect of obesity on circulating concentrations and gene and protein expression levels of LCN2 in human visceral adipose tissue (VAT) as well as its involvement in inflammation. VAT biopsies from 47 subjects were used in the study. Real-time PCR and Western-blot analyses were performed to quantify levels of LCN2 in VAT as well as the association with other genes implicated in inflammatory pathways. Forty-four serum samples were used to analyze the circulating concentrations of LCN2. Zymography analysis was used to determine the activity of matrix metalloproteinase (MMP) in VAT. Obese patients exhibited increased mRNA (p < 0.0001) and protein (p = 0.017) expression levels of LCN2 compared to lean subjects. Although no differences in plasma LCN2 concentrations were observed, increased circulating LCN2/MMP-9 complex levels were found (p = 0.038) in the obese group. Moreover, obese individuals showed increased (p < 0.01) activity of MMP-2 and MMP-9/LCN2 complex, while a positive correlation (p < 0.01) between MMP-2 and MMP-9 activities and BMI was observed. Gene and protein expression levels of LCN2 in VAT were positively associated with inflammatory markers (p < 0.01). These findings represent the first observation that mRNA and protein levels of LCN2 are increased in human VAT of obese subjects. Furthermore, LCN2 is associated with MMP-2 and MMP-9 activities as well as with pro-inflammatory markers suggesting its potential involvement in the low-grade chronic inflammation accompanying obesity.

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Acknowledgements

The authors have nothing to disclose. This work was supported by FIS, PI061458, PI06/90288, and PI081146 from the Spanish Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, by the Department of Health (20/2005 and 3/2006) and by the Department of Education of the Gobierno de Navarra of Spain. The authors gratefully acknowledge the valuable collaboration of the Department of Surgery and all the members of the Multidisciplinary Obesity Team. We extend a special thanks to Dr. Patricia Fernández-Robredo for her valuable help in determining matrix metalloproteinase activity. 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 Universitaria de Navarra, University of Navarra, Pamplona, Spain

    V. Catalán, J. Gómez-Ambrosi, A. Rodríguez, B. Ramírez & G. Frühbeck

  2. Department of Endocrinology, Clínica Universitaria de Navarra, University of Navarra, Avda. Pío XII, 36, Pamplona, 31008, Spain

    C. Silva, J. Salvador & G. Frühbeck

  3. Department of Surgery, Clínica Universitaria de Navarra, University of Navarra, Pamplona, Spain

    F. Rotellar & J. A. Cienfuegos

  4. Department of Biochemistry, Clínica Universitaria de Navarra, University of Navarra, Pamplona, Spain

    M. J. Gil

  5. CIBER Fisiopatología de la Obesidad y Nutrición http://ww.ciberobn.es/

    V. Catalán, J. Gómez-Ambrosi, A. Rodríguez, B. Ramírez, C. Silva, F. Rotellar, M. J. Gil, J. A. Cienfuegos, J. Salvador & G. Frühbeck

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  1. V. Catalán
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Correspondence to G. Frühbeck.

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Catalán, V., Gómez-Ambrosi, J., Rodríguez, A. et al. Increased adipose tissue expression of lipocalin-2 in obesity is related to inflammation and matrix metalloproteinase-2 and metalloproteinase-9 activities in humans. J Mol Med 87, 803–813 (2009). https://doi.org/10.1007/s00109-009-0486-8

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