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B cell translocation gene 2 (Btg2) is regulated by Stat3 signaling and inhibits adipocyte differentiation
Suji Kim1, Joung-Woo Hong2, Kye Won Park3
1Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon, 16419, Korea.
Abstract:
Btg2, a member of a family of antiproliferative proteins, is involved in downregulation of the JAK2-Stat3 signaling pathway. Here, we present evidence that the inhibitory effect of Btg2 on adipogenesis is suppressed by the proadipogenic activity of the Stat3 signaling pathway. Btg2 expression fluctuates during adipogenic differentiation of preadipocytes. Btg2 is also expressed at different levels in fat tissues from lean and obese mice. Furthermore, knockdown of Btg2 expression enhanced lipid accumulation and upregulated the expression of adipogenic marker genes. To gain insights into the molecular mechanisms of Btg2 action in adipocytes, adipocytes were treated with previously identified bioactive compounds and the expression of Btg2 was assessed. This effort identified the small molecule WP1066, a known Stat3 inhibitor, as an inducer of Btg2 expression. In line with this observation, siRNA-mediated silencing of Stat3 resulted in upregulated Btg2 expression and decreased lipid accumulation. Furthermore, siRNA-mediated silencing of Btg2 attenuated WP1066-mediated inhibition of adipocyte differentiation. We discuss a model for the role of Btg2 in adipogenesis and propose that Btg2 and Stat3 act in a functional hierarchy.
Insights
Btg2 protein inhibits fat cell formation (adipogenesis), but this effect is blocked by the Stat3 pathway. Stat3 inhibition increases Btg2, revealing a key regulatory relationship in fat tissue.
Area of Science:
- Biochemistry
- Molecular Biology
- Cellular Biology
Background:
- Btg2 is an antiproliferative protein that downregulates the JAK2-Stat3 signaling pathway.
- The Stat3 pathway promotes fat cell formation (adipogenesis).
Purpose of the Study:
- To investigate the role of Btg2 in adipogenesis and its relationship with the Stat3 signaling pathway.
- To elucidate the molecular mechanisms by which Btg2 influences adipocyte differentiation.
Main Methods:
- Assessing Btg2 expression during adipogenic differentiation.
- Analyzing Btg2 levels in fat tissues from lean and obese mice.
- Investigating the effect of Btg2 knockdown on lipid accumulation and adipogenic gene expression.
- Treating adipocytes with compounds to assess Btg2 expression changes.
- Utilizing Stat3 inhibitors (WP1066) and siRNA-mediated gene silencing.
Main Results:
- Btg2 expression varies during adipocyte differentiation and differs between lean and obese mice.
- Btg2 knockdown enhances lipid accumulation and upregulates adipogenic markers.
- The Stat3 inhibitor WP1066 induces Btg2 expression.
- Stat3 silencing increases Btg2 expression and reduces lipid accumulation.
- Btg2 silencing counteracts WP1066's inhibition of adipogenesis.
Conclusions:
- Btg2's inhibitory effect on adipogenesis is suppressed by Stat3 signaling.
- Btg2 and Stat3 are proposed to function in a hierarchical manner in adipogenesis.
- Btg2 acts as a negative regulator of adipogenesis, with its function modulated by Stat3 activity.
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