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

C. Lagathu, C. Christodoulides, C. Y. Tan, S. Virtue, M. Laudes, M. Campbell, K. Ishikawa, F. Ortega, F. J. Tinahones, J.-M. Fernández-Real, Matej Orešič, J. K. Sethi (Corresponding Author), A. Vidal-Puig (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

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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.

Original languageEnglish
Pages (from-to)1695-1705
JournalInternational Journal of Obesity
Volume34
DOIs
Publication statusPublished - 2010
MoE publication typeA1 Journal article-refereed

Fingerprint

Tissue Expansion
Morbid Obesity
Adipose Tissue
Adipogenesis
Catenins
Obesity
Adipocytes
frizzled related protein-1
Wnt Signaling Pathway
High Fat Diet
Longitudinal Studies

Keywords

  • metabolic syndrome
  • adipose tissue
  • adipogenesis
  • Wnt signaling

Cite this

Lagathu, C., Christodoulides, C., Tan, C. Y., Virtue, S., Laudes, M., Campbell, M., ... Vidal-Puig, A. (2010). Secreted frizzled-related protein 1 regulates adipose tissue expansion and is dysregulated in severe obesity. International Journal of Obesity, 34, 1695-1705. https://doi.org/10.1038/ijo.2010.107
Lagathu, C. ; Christodoulides, C. ; Tan, C. Y. ; Virtue, S. ; Laudes, M. ; Campbell, M. ; Ishikawa, K. ; Ortega, F. ; Tinahones, F. J. ; Fernández-Real, J.-M. ; Orešič, Matej ; Sethi, J. K. ; Vidal-Puig, A. / Secreted frizzled-related protein 1 regulates adipose tissue expansion and is dysregulated in severe obesity. In: International Journal of Obesity. 2010 ; Vol. 34. pp. 1695-1705.
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title = "Secreted frizzled-related protein 1 regulates adipose tissue expansion and is dysregulated in severe obesity",
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.",
keywords = "metabolic syndrome, adipose tissue, adipogenesis, Wnt signaling",
author = "C. Lagathu and C. Christodoulides and Tan, {C. Y.} and S. Virtue and M. Laudes and M. Campbell and K. Ishikawa and F. Ortega and Tinahones, {F. J.} and J.-M. Fern{\'a}ndez-Real and Matej Orešič and Sethi, {J. K.} and A. Vidal-Puig",
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Lagathu, C, Christodoulides, C, Tan, CY, Virtue, S, Laudes, M, Campbell, M, Ishikawa, K, Ortega, F, Tinahones, FJ, Fernández-Real, J-M, Orešič, M, Sethi, JK & Vidal-Puig, A 2010, 'Secreted frizzled-related protein 1 regulates adipose tissue expansion and is dysregulated in severe obesity', International Journal of Obesity, vol. 34, pp. 1695-1705. https://doi.org/10.1038/ijo.2010.107

Secreted frizzled-related protein 1 regulates adipose tissue expansion and is dysregulated in severe obesity. / Lagathu, C.; Christodoulides, C.; Tan, C. Y.; Virtue, S.; Laudes, M.; Campbell, M.; Ishikawa, K.; Ortega, F.; Tinahones, F. J.; Fernández-Real, J.-M.; Orešič, Matej; Sethi, J. K. (Corresponding Author); Vidal-Puig, A. (Corresponding Author).

In: International Journal of Obesity, Vol. 34, 2010, p. 1695-1705.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Secreted frizzled-related protein 1 regulates adipose tissue expansion and is dysregulated in severe obesity

AU - Lagathu, C.

AU - Christodoulides, C.

AU - Tan, C. Y.

AU - Virtue, S.

AU - Laudes, M.

AU - Campbell, M.

AU - Ishikawa, K.

AU - Ortega, F.

AU - Tinahones, F. J.

AU - Fernández-Real, J.-M.

AU - Orešič, Matej

AU - Sethi, J. K.

AU - Vidal-Puig, A.

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

KW - metabolic syndrome

KW - adipose tissue

KW - adipogenesis

KW - Wnt signaling

U2 - 10.1038/ijo.2010.107

DO - 10.1038/ijo.2010.107

M3 - Article

VL - 34

SP - 1695

EP - 1705

JO - International Journal of Obesity

JF - International Journal of Obesity

SN - 0307-0565

ER -