Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Centre , Xi'an, Shaanxi, China.
Laboratory Animal Center, Xi'an Jiaotong University Health Science Centre , Xi'an, Shaanxi, China.
Adipocyte. 2020 Dec;9(1):374-383. doi: 10.1080/21623945.2020.1792614.
Secreted frizzled-related protein (SFRP) 4 is an extracellular antagonist of Wnt signalling that regulates adipogenesis, and is highly in the visceral adipose tissue of obese individuals. However, it is still unclear how exactly SFRP4 regulates the secretion of adipokines in the adipose tissue , an event that is closely related to the pathogenesis of obesity and insulin resistance. In this study, we generated transgenic (Tg) mice overexpressing in the liver and investigated SFRP4 role in adipokine secretion in mice on a regular normal diet. In Tg mice, SFRP4 protein was overexpressed in the liver, as compared to wild-type littermates (non-Tg), and released into the blood. Moreover, the size of adipocytes was smaller in the visceral adipose tissue of Tg mice compared to controls. Additionally, overexpression affected the expression of genes related to adipocyte differentiation, causing the upregulation of adiponectin and glucose transporter 4, and the downregulation of CCAAT/enhancer-binding protein-β, in both visceral and subcutaneous adipose tissue. However, there was no difference in body weight or body composition between Tg and non-Tg mice. In summary, our data showed that overexpression altered adipocyte size and adipokine secretion, possibly affecting adipocyte differentiation, obesity, and glucose metabolism.
分泌型卷曲相关蛋白 4(SFRP4)是一种细胞外 Wnt 信号通路拮抗剂,可调节脂肪生成,在肥胖个体的内脏脂肪组织中高度表达。然而,SFRP4 如何确切调节脂肪组织中脂肪因子的分泌,这一事件与肥胖和胰岛素抵抗的发病机制密切相关,目前仍不清楚。在本研究中,我们生成了肝脏过表达 SFRP4 的转基因(Tg)小鼠,并在正常饮食条件下研究了 SFRP4 在小鼠脂肪因子分泌中的作用。在 Tg 小鼠中,SFRP4 蛋白在肝脏中过度表达,与野生型同窝仔鼠(非 Tg)相比,并释放到血液中。此外,与对照组相比,Tg 小鼠的内脏脂肪组织中的脂肪细胞较小。此外,过表达影响与脂肪细胞分化相关的基因的表达,导致脂肪细胞分泌的脂联素和葡萄糖转运蛋白 4 上调,以及 CCAAT/增强子结合蛋白-β 在内脏和皮下脂肪组织中的下调。然而,Tg 和非 Tg 小鼠之间的体重或体成分没有差异。总之,我们的数据表明,SFRP4 过表达改变了脂肪细胞大小和脂肪因子分泌,可能影响脂肪细胞分化、肥胖和葡萄糖代谢。