Secreted frizzled-related protein 1 regulates adipose tissue expansion and is dysregulated in severe obesity
Autor: | Jaswinder K. Sethi, Ko Ishikawa, Matej Orešič, Antonio Vidal-Puig, Matthias Laudes, Francisco Ortega, Mark Campbell, Francisco J. Tinahones, Constantinos Christodoulides, José Manuel Fernández-Real, Sam Virtue, Chong Yew Tan, C Lagathu |
---|---|
Rok vydání: | 2010 |
Předmět: |
Male
medicine.medical_specialty Adipose Tissue White Endocrinology Diabetes and Metabolism Cellular differentiation Adipose tissue macrophages Adipocytes White Adipose tissue Gene Expression Medicine (miscellaneous) Biology Wnt Signalling metabolic syndrome Article adipogenesis Mice Paracrine signalling SDG 3 - Good Health and Well-being Secreted frizzled-related protein 1 Internal medicine medicine Animals Humans Obesity beta Catenin Aged Adipogenesis Nutrition and Dietetics Intracellular Signaling Peptides and Proteins Wnt signaling pathway Proteins Cell Differentiation Wnt signaling Metabolic syndrome adipose tissue Obesity Morbid Wnt Proteins Endocrinology Female Ectopic expression Signal Transduction |
Zdroj: | International journal of obesity (2005) 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, M, Sethi, J K & 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 |
ISSN: | 1476-5497 0307-0565 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |