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Secreted frizzled-related protein 1 regulates adipose tissue expansion and is dysregulated in severe obesity

International Journal of Obesity volume 34, pages 1695–1705 (2010)Cite this article

Subjects

Abstract

Aim:

The Wnt/β-catenin signaling network offers potential targets to diagnose and uncouple obesity from its metabolic complications. In this study, we investigate the role of the Wnt antagonist, secreted frizzled-related protein 1 (SFRP1), in promoting adipogenesis in vitro and adipose tissue expansion in vivo.

Methods:

We use a combination of human and murine, in vivo and in vitro models of adipogenesis, adipose tissue expansion and obesity-related metabolic syndrome to profile the involvement of SFRP1.

Results:

SFRP1 is expressed in both murine and human mature adipocytes. The expression of SFRP1 is induced during in vitro adipogenesis, and SFRP1 is preferentially expressed in mature adipocytes in human adipose tissue. Constitutive ectopic expression of SFRP1 is proadipogenic and inhibits the Wnt/β-catenin signaling pathway. In vivo endogenous levels of adipose SFRP1 are regulated in line with proadipogenic states. However, in longitudinal studies of high-fat-diet-fed mice, we observed a dynamic temporal but biphasic regulation of endogenous SFRP1. In agreement with this profile, we observed that SFRP1 expression in human tissues peaks in patients with mild obesity and gradually falls in morbidly obese subjects.

Conclusions:

Our results suggest that SFRP1 is an endogenous modulator of Wnt/β-catenin signaling and participates in the paracrine regulation of human adipogenesis. The reduced adipose expression of SFRP1 in morbid obesity and its knock-on effect to prevent further adipose tissue expansion may contribute to the development of metabolic complications in these individuals.

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Acknowledgements

We thank the Addenbrooke's hospital surgeons for performing the adipose tissue biopsies. This research is funded by the Biotechnology and Biological Science Research Council (BBSRC), the Medical Research Council (MRC) and the European Union Sixth Framework Programme on Hepatic and Adipose tissue functions in the metabolic syndrome (EU-FP6 HEPADIP) (AV-P and JKS). We also acknowledge the support received from ALFEDIAM and Marie Curie Postdoctoral fellowship (CL), MRC Doctoral Studentships (CC and SV), MRC Career Establishment Award (AV-P) and BBSRC David Phillips Fellowship (JKS).

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Institute of Metabolic Science—Metabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK

    C Lagathu, C Y Tan, S Virtue, M Laudes, M Campbell, K Ishikawa, J K Sethi & A Vidal-Puig

  2. Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK

    C Christodoulides

  3. Department of Diabetes, Endocrinology and Nutrition, Hospital of Girona Dr Josep Trueta, Biomedical Research Institute and CIBEROBN Fisiopatología de la Obesidad y Nutrición CB06/03/010, Girona, Spain

    F Ortega & J-M Fernández-Real

  4. Service of Endocrinology and Nutrition, Hospital Clinico Universitario Virgen de Victoria de Malaga, Malaga, Spain

    F J Tinahones

  5. VTT Technical Research Centre of Finland, Espoo, Finland

    M Orešič

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  1. C Lagathu
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Corresponding authors

Correspondence to J K Sethi or A Vidal-Puig.

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Supplementary Information accompanies the paper on International Journal of Obesity website

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Lagathu, C., Christodoulides, C., Tan, C. et al. Secreted frizzled-related protein 1 regulates adipose tissue expansion and is dysregulated in severe obesity. Int J Obes 34, 1695–1705 (2010). https://doi.org/10.1038/ijo.2010.107

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