State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P.R. China.
National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P.R. China.
Cell Biol Int. 2018 Jan;42(1):63-74. doi: 10.1002/cbin.10862. Epub 2017 Oct 16.
The early stage of obesity is an important stage in the development of obesity. However, there are few studies which explored the property or changes in obesity at early stage especially involving Wnt5a. The associated gene expression of Wnt5a on cell regeneration and the effect of Wnt5a on rat adipose-derived stem cell (rASC) proliferation and adipogenesis need additional study. Here, we investigated the changes in obesity at early stage and how Wnt5a regulates rASC regeneration, proliferation, and adipogenesis. Our data revealed that obesity at early stage measured by Lee index presented a state with impaired adipogenesis and more infiltrated inflammatory cells but without significant changes in adipocyte sizes and inflammatory factors. The process might be associated with anti-canonical Wnt pathway and a reciprocal Wnt5a/JNK pathway. Besides the gene expression of Wnt5a decreased from cell passage 1 to passage 3. The cell proliferation was regulated by increasing dose of Wnt5a with the maximal effect at 50 ng/mL and 50 ng/mL Wnt5a suppressed adipogenic differentiation at middle-late stage of adipogenesis via anti-β-catenin and a mitogen-activated protein kinase (MAPK) signaling-independent manner. Accordingly, the research helps to gain further insights into the early stage of obesity and its associated changes on a cellular and molecular level.
肥胖的早期阶段是肥胖发展的重要阶段。然而，很少有研究探讨肥胖早期阶段的特征或变化，特别是涉及 Wnt5a 的研究。Wnt5a 对细胞再生的相关基因表达以及 Wnt5a 对大鼠脂肪源性干细胞（rASC）增殖和脂肪生成的影响需要进一步研究。在这里，我们研究了肥胖早期阶段的变化，以及 Wnt5a 如何调节 rASC 的再生、增殖和脂肪生成。我们的数据表明，Lee 指数衡量的肥胖早期阶段表现为脂肪生成受损和更多浸润的炎症细胞，但脂肪细胞大小和炎症因子没有明显变化。这个过程可能与非经典 Wnt 途径和相互的 Wnt5a/JNK 途径有关。此外，Wnt5a 的基因表达从细胞传代 1 到传代 3 降低。细胞增殖受 Wnt5a 浓度增加的调节，在 50ng/ml 时达到最大效应，而 50ng/ml 的 Wnt5a 通过抗 β-catenin 和非丝裂原活化蛋白激酶（MAPK）信号通路独立的方式抑制脂肪生成的中晚期分化。因此，这项研究有助于深入了解肥胖的早期阶段及其在细胞和分子水平上的相关变化。
