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Gremlin 2 inhibits adipocyte differentiation through activation of Wnt/β-catenin signaling
Qing Wu1, Shi-Guo Tang2, Zhong-Ming Yuan3
1Department of Geriatrics Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
Abstract:
The primary function of white adipose tissues is to store excess energy. The current study aimed to investigate the roles of Gremlin 2 (Grem2), a glycoprotein in adipogenesis. Using polymerase chain reaction‑based microarrays, it was determined that Grem2 was markedly downregulated in adipose tissues from obese animals and humans. In addition, 3T3‑L1 cells were used to investigate the details of the mechanisms underlying the anti‑adipogenic effects of Grem2. Grem2 expression was markedly decreased upon the induction of adipocyte differentiation, as demonstrated by reverse transcription‑quantitative polymerase chain reaction and western blot analysis. Notably, Grem2 overexpression inhibited adipogenesis, while knockdown of Grem2 led to an increase in adipogenesis. At the molecular level, Grem2 promotes nuclear translocation of β‑catenin, an integral Wnt signaling component. Consistently, inhibition of Wnt/β‑catenin signaling using a retrovirus targeting the β‑catenin coding region attenuated the anti‑adipogenic effects of Grem2. Therefore, to the best of our knowledge, the current study shows for the first time that Grem2 may be an important regulator of adipocyte differentiation.
Insights
Gremlin 2 (Grem2) is downregulated in obesity and inhibits adipogenesis by promoting Wnt/β-catenin signaling. This study identifies Grem2 as a key regulator of white adipose tissue differentiation.
Area of Science:
- Molecular Biology
- Cell Biology
- Endocrinology
Background:
- White adipose tissue (WAT) stores energy and plays a crucial role in metabolic homeostasis.
- Adipogenesis, the process of fat cell differentiation, is dysregulated in obesity.
- Gremlin 2 (Grem2) is a glycoprotein with largely unknown functions in metabolic tissues.
Purpose of the Study:
- To investigate the role of Gremlin 2 (Grem2) in adipogenesis and its potential involvement in obesity.
- To elucidate the molecular mechanisms by which Grem2 influences adipocyte differentiation.
Main Methods:
- Polymerase chain reaction (PCR)-based microarrays to assess Grem2 expression in obese adipose tissue.
- Reverse transcription-quantitative PCR (RT-qPCR) and Western blot analysis in 3T3-L1 cells.
- Grem2 overexpression and knockdown experiments in 3T3-L1 cells.
- Analysis of Wnt/β-catenin signaling pathway activation.
Main Results:
- Grem2 expression was significantly downregulated in adipose tissues of obese animals and humans.
- Grem2 expression decreased during adipocyte differentiation of 3T3-L1 cells.
- Grem2 overexpression inhibited adipogenesis, while Grem2 knockdown enhanced it.
- Grem2 promoted the nuclear translocation of β-catenin, a key component of the Wnt signaling pathway.
- Inhibition of Wnt/β-catenin signaling abrogated the anti-adipogenic effects of Grem2.
Conclusions:
- Gremlin 2 (Grem2) acts as a novel negative regulator of adipogenesis.
- Grem2 influences adipocyte differentiation through the Wnt/β-catenin signaling pathway.
- Grem2 may represent a potential therapeutic target for obesity and related metabolic disorders.
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