Secreted frizzled-related protein 1 regulates adipose tissue expansion and is dysregulated in severe obesity.
Secreted frizzled-related protein 1 regulates adipose tissue expansion and is dysregulated in severe obesity.
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DOI：
10.1038/ijo.2010.107
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发表时间：
2010-12
影响因子：
4.9
通讯作者：
Vidal-Puig, A.
中科院分区：
文献类型：
--
作者：
Lagathu, C.;Christodoulides, C.;Tan, C. Y.;Virtue, S.;Laudes, M.;Campbell, M.;Ishikawa, K.;Ortega, F.;Tinahones, F. J.;Fernandez-Real, J-M;Oresic, M.;Sethi, J. K.;Vidal-Puig, A.
Wnt/β-catenin信号网络为诊断肥胖及其代谢并发症提供了潜在的靶点。在这里，我们研究的作用Wnt拮抗剂，分泌卷曲相关蛋白1（SFRP 1）在促进体外脂肪形成和体内脂肪组织扩张。我们使用人和鼠的组合，在体内和体外模型的脂肪形成，脂肪组织扩张和肥胖相关的代谢综合征的轮廓SFRP 1的参与。分泌型卷曲相关蛋白1（SFRP 1）在鼠和人成熟脂肪细胞中表达。SFRP 1的表达在体外脂肪形成过程中被诱导，并且SFRP 1优先在人脂肪组织中的成熟脂肪细胞中表达。SFRP 1的组成性异位表达是促脂肪形成的，并抑制Wnt/β-catenin信号通路。体内内源性脂肪SFRP 1水平的调节与前脂肪形成状态一致。然而，在高脂饮食喂养的小鼠的纵向研究中，我们观察到内源性SFRP 1的动态时间但双相调节。与此情况一致，我们观察到SFRP 1在人组织中的表达在轻度肥胖患者中达到峰值，在病态肥胖受试者中逐渐福尔斯下降。我们的研究结果表明，SFRP 1是Wnt/β-catenin信号转导的内源性调节剂，并参与人类脂肪形成的旁分泌调节。在病态肥胖症中，SFRP 1的脂肪表达减少及其防止脂肪组织进一步扩张的连锁效应可能有助于这些个体中代谢并发症的发展。
The Wnt/β-catenin signalling network offers potential targets to diagnose and uncouple obesity from its metabolic complications. Here 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. 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. Secreted Frizzled related protein 1 (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 signalling 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. Our results suggest that SFRP1 is an endogenous modulator of Wnt/β-catenin signalling 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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DOI：
10.1074/jbc.m310240200
发表时间：
2004-03-19
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Laudes M;Christodoulides C;Sewter C;Rochford JJ;Considine RV;Sethi JK;Vidal-Puig A;O'Rahilly S
通讯作者：
O'Rahilly S
影响因子：
10.9
作者：
Christodoulides, Constantinos;Lagathu, Claire;Sethi, Jaswinder K.;Vidal-Puig, Antonio
通讯作者：
Vidal-Puig, Antonio
DOI：
10.1016/j.bbrc.2004.03.152
发表时间：
2004-05-14
影响因子：
3.1
作者：
Yang, XL;Jansson, PA;Smith, U
通讯作者：
Smith, U
影响因子：
7.7
作者：
Lagathu, Claire;Christodoulides, Constantinos;Virtue, Sam;Cawthorn, William P.;Franzin, Chiara;Kimber, Wendy A.;Nora, Edoardo Dalla;Campbell, Mark;Medina-Gomez, Gema;Cheyette, Benjamin N. R.;Vidal-Puig, Antonio J.;Sethi, Jaswinder K.
通讯作者：
Sethi, Jaswinder K.
影响因子：
9.8
作者：
Virtue S;Vidal-Puig A
通讯作者：
Vidal-Puig A