Mai Yin, Zhang Zhenyu, Yang Hao, Dong Peiyue, Chu Guiyan, Yang Gongshe, Sun Shiduo
Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, 22 Xinong Road, Yangling, Shaanxi 712100, China.
Biochem Cell Biol. 2014 Jun;92(3):172-82. doi: 10.1139/bcb-2014-0011. Epub 2014 May 6.
The process of differentiation from preadipocytes to adipocytes contributes to adipose tissue expansion in obesity. Blocking adipogenesis may be conducive to the etiology of obesity-related diseases. BMP and activin membrane-bound inhibitor (BAMBI) is a transmembrane protein, which was identified as a target of β-catenin in colorectal and hepatocellular tumor cells. However, whether BAMBI affects adipogenesis by Wnt/β-catenin signaling remains to be explored. In this study, we distinguish BAMBI as an inhibitor of preadipocytes differentiation. We found that BAMBI was downregulated during preadipocytes differentiation. Knockdown of BAMBI increased adipogenesis and blocked Wnt/β-catenin signaling by repressing β-catenin accumulation. In BAMBI overexpression cells, lipid accumulation was reduced by promoting nuclear translocation of β-catenin. Lithium chloride (LiCl) is an activator of Wnt/β-catenin signaling, which is an inhibitor of glycogen synthetase kinase-3 (GSK-3), maintaining the stability of β-catenin in cytosolic. We showed BAMBI strengthened the anti-adipogenic effects of LiCl. In addition, the results indicated that BAMBI was upregulated by β-catenin. These observations illuminated that BAMBI inhibits adipogenesis by a feedback loop (BAMBI→β-catenin nuclear translocation→BAMBI), which forms with Wnt/β-catenin signaling.
从前脂肪细胞到脂肪细胞的分化过程促使肥胖状态下脂肪组织的扩张。阻断脂肪生成可能有助于肥胖相关疾病的病因研究。骨形态发生蛋白和激活素膜结合抑制剂（BAMBI）是一种跨膜蛋白，在结肠直肠癌和肝细胞肿瘤细胞中被确定为β-连环蛋白的靶点。然而，BAMBI是否通过Wnt/β-连环蛋白信号通路影响脂肪生成仍有待探索。在本研究中，我们将BAMBI鉴定为前脂肪细胞分化的抑制剂。我们发现，在前脂肪细胞分化过程中BAMBI表达下调。敲低BAMBI可增加脂肪生成，并通过抑制β-连环蛋白的积累来阻断Wnt/β-连环蛋白信号通路。在BAMBI过表达细胞中，通过促进β-连环蛋白的核转位减少了脂质积累。氯化锂（LiCl）是Wnt/β-连环蛋白信号通路的激活剂，它是糖原合成酶激酶-3（GSK-3）的抑制剂，可维持β-连环蛋白在细胞质中的稳定性。我们发现BAMBI增强了LiCl的抗脂肪生成作用。此外，结果表明β-连环蛋白可上调BAMBI的表达。这些观察结果表明，BAMBI通过与Wnt/β-连环蛋白信号通路形成的反馈环（BAMBI→β-连环蛋白核转位→BAMBI）抑制脂肪生成。
