School of Agricultural Engineering and Food Science, Shandong University of Technology, Zibo 255049, China.
Anti-Aging & Regenerative Medicine Research Institution, School of Life Sciences, Shandong University of Technology, Zibo 255049, China.
Cells. 2019 Aug 30;8(9):1011. doi: 10.3390/cells8091011.
There are 19 Wnt genes in mammals that belong to 12 subfamilies. Wnt signaling pathways participate in regulating numerous homeostatic and developmental processes in animals. However, the function of Wnt10b in fatty acid synthesis remains unclear in fish species. In the present study, we uncovered the role of the Wnt10b signaling pathway in the regulation of fatty acid synthesis in the muscle of zebrafish. The gene of Wnt10b was overexpressed in the muscle of zebrafish using pEGFP-N1-Wnt10b vector injection, which significantly decreased the expression of glycogen synthase kinase 3β (GSK-3β), but increased the expression of β-catenin, peroxisome proliferators-activated receptor γ (PPARγ), and CCAAT/enhancer binding protein α (C/EBPα). Moreover, the activity and mRNA expression of key lipogenic enzymes ATP-citrate lyase (ACL), acetyl-CoA carboxylase (ACC) and fatty acid synthetase (FAS), and the content of non-esterified fatty acids (NEFA), total cholesterol (TC), and triglyceride (TG) were also significantly decreased. Furthermore, interference of the Wnt10b gene significantly inhibited the expression of β-catenin, PPARγ, and C/EBPα, but significantly induced the expression of GSK-3β, FAS, ACC, and ACL. The content of NEFA, TC, and TG as well as the activity of FAS, ACC, and ACL significantly increased. Thus, our results showed that Wnt10b participates in regulating fatty acid synthesis via β-catenin, C/EBPα and PPARγ in the muscle of zebrafish.
哺乳动物中有 19 种 Wnt 基因,属于 12 个亚家族。Wnt 信号通路参与调节动物体内的许多动态平衡和发育过程。然而,Wnt10b 在鱼类脂肪酸合成中的功能尚不清楚。在本研究中,我们揭示了 Wnt10b 信号通路在调控斑马鱼肌肉中脂肪酸合成中的作用。通过 pEGFP-N1-Wnt10b 载体注射在斑马鱼肌肉中过表达 Wnt10b 基因,显著降低了糖原合酶激酶 3β(GSK-3β)的表达,但增加了β-catenin、过氧化物酶体增殖物激活受体 γ(PPARγ)和 CCAAT/增强子结合蛋白α(C/EBPα)的表达。此外,关键的脂肪生成酶 ATP-柠檬酸裂解酶(ACL)、乙酰辅酶 A 羧化酶(ACC)和脂肪酸合成酶(FAS)的活性和 mRNA 表达,以及非酯化脂肪酸(NEFA)、总胆固醇(TC)和甘油三酯(TG)的含量也显著降低。此外,Wnt10b 基因的干扰显著抑制了β-catenin、PPARγ 和 C/EBPα 的表达,但显著诱导了 GSK-3β、FAS、ACC 和 ACL 的表达。NEFA、TC 和 TG 的含量以及 FAS、ACC 和 ACL 的活性显著增加。因此,我们的结果表明,Wnt10b 通过β-catenin、C/EBPα 和 PPARγ 参与调节斑马鱼肌肉中的脂肪酸合成。