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

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

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 peroxiso

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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