View in EDS

Siah2 Protein Mediates Early Events in Commitment to an Adipogenic Pathway.

Saved in:
Bibliographic Details
Title: Siah2 Protein Mediates Early Events in Commitment to an Adipogenic Pathway.
Authors: Kilroy, Gail1, Burk, David H.1, Floyd, Z. Elizabeth1 Elizabeth.Floyd@pbrc.edu
Source: Journal of Biological Chemistry. 12/30/2016, Vol. 291 Issue 53, p27289-27297. 10p.
Subjects: Adipose tissue diseases, Tissue expansion, Adipogenesis, Obesity, Hypertrophy
Abstract: Adipose tissue expansion occurs by increasing the size of existing adipocytes or by increasing the number of adipocytes via adipogenesis. Adipose tissue dysfunction in obesity is associated with adipocyte hypertrophy and impaired adipogenesis. We recently demonstrated that deletion of the ubiquitin ligase Siah2 is associated with enlarged adipocytes in lean or obese mice. In this study, we find that adipogenesis is impaired in 3T3-L1 preadipocytes stably transfected with Siah2 shRNA and that overexpression of Siah2 in non-precursor fibroblasts promotes adipogenesis. In the 3T3-L1 model, loss of Siah2 is associated with sustained β-catenin expression post-induction, but depletion of β-catenin only partially restores PPARγ expression and adipocyte formation. Using wild-type and Siah2-/- adipose tissue and adipose stromal vascular cells, we observe that Siah2 influences the expression of several factors that control adipogenesis, including Wnt pathway genes, β-catenin, Zfp432, and Bmp-4. Consistent with increased β-catenin levels in shSiah2 preadipocytes, Wnt10b is elevated in Siah2-/- adipose tissue and remains elevated in Siah2-/- primary stromal cells after addition of the induction mixture. However, addition of BMP-4 to Siah2-/- stromal cells reduces Wnt10b expression, reduces Zfp521 protein levels, and increases expression of Zfp423, a transcriptional regulator of peroxisome proliferator-activated receptor γ expression that controls commitment to adipogenesis and is repressed by Zfp521. These results indicate that Siah2 acts upstream of BMP-4 to regulate factors that control the commitment of adipocyte progenitors to an adipogenic pathway. Our findings reveal an essential role for Siah2 in the early events that signal undifferentiated progenitor cells to become mature adipocytes. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
Description
Abstract:Adipose tissue expansion occurs by increasing the size of existing adipocytes or by increasing the number of adipocytes via adipogenesis. Adipose tissue dysfunction in obesity is associated with adipocyte hypertrophy and impaired adipogenesis. We recently demonstrated that deletion of the ubiquitin ligase Siah2 is associated with enlarged adipocytes in lean or obese mice. In this study, we find that adipogenesis is impaired in 3T3-L1 preadipocytes stably transfected with Siah2 shRNA and that overexpression of Siah2 in non-precursor fibroblasts promotes adipogenesis. In the 3T3-L1 model, loss of Siah2 is associated with sustained β-catenin expression post-induction, but depletion of β-catenin only partially restores PPARγ expression and adipocyte formation. Using wild-type and Siah2-/- adipose tissue and adipose stromal vascular cells, we observe that Siah2 influences the expression of several factors that control adipogenesis, including Wnt pathway genes, β-catenin, Zfp432, and Bmp-4. Consistent with increased β-catenin levels in shSiah2 preadipocytes, Wnt10b is elevated in Siah2-/- adipose tissue and remains elevated in Siah2-/- primary stromal cells after addition of the induction mixture. However, addition of BMP-4 to Siah2-/- stromal cells reduces Wnt10b expression, reduces Zfp521 protein levels, and increases expression of Zfp423, a transcriptional regulator of peroxisome proliferator-activated receptor γ expression that controls commitment to adipogenesis and is repressed by Zfp521. These results indicate that Siah2 acts upstream of BMP-4 to regulate factors that control the commitment of adipocyte progenitors to an adipogenic pathway. Our findings reveal an essential role for Siah2 in the early events that signal undifferentiated progenitor cells to become mature adipocytes. [ABSTRACT FROM AUTHOR]
ISSN:00219258
DOI:10.1074/jbc.M116.744672