College of Human Development and Health, National Taipei University of Nursing and Health Sciences, Taipei 112303, Taiwan.
Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan.
Int J Mol Sci. 2022 May 14;23(10):5488. doi: 10.3390/ijms23105488.
Plasma and tissue zinc ion levels are associated with the development of obesity. Previous studies have suggested that zinc ions may regulate adipocyte metabolism and that nitric oxide (NO) plays a pivotal role in the regulation of adipocyte physiology. Our previous study showed that chronic NO deficiency causes a significant decrease in adipose tissue mass in rats. Studies also suggested that zinc ions play an important modulatory role in regulating NO function. This study aims to explore the role of zinc ions in NO-regulated adipocyte differentiation. We hypothesized that NO could increase intracellular Zn level and then stimulate adipocyte differentiation. ZnCl and the NO donor, NONOate, were used to explore the effects of Zn and NO on adipocyte differentiation. Regulatory mechanisms of NO on intracellular Zn mobilization were determined by detection. Then, Zn-selective chelator TPEN was used to clarify the role of intracellular Zn on NO-regulated adipocyte differentiation. Furthermore, the relationship between adipocyte size, Zn level, and NOS expression in human subcutaneous fat tissue was elucidated. Results showed that both ZnCl and NO stimulated adipocyte differentiation in a dose-dependent manner. NO stimulated intracellular Zn mobilization in adipocytes through the guanylate cyclase (GC)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) pathway, and NO-stimulated adipocyte differentiation was Zn-dependent. In human subcutaneous adipose tissue, adipocyte size was negatively correlated with expression of eNOS. In conclusion, NO treatment stimulates intracellular Zn mobilization through the GC/cGMP/PKG pathway, subsequently stimulating adipocyte differentiation.
血浆和组织锌离子水平与肥胖的发展有关。先前的研究表明，锌离子可能调节脂肪细胞代谢，一氧化氮（NO）在调节脂肪细胞生理中起着关键作用。我们之前的研究表明，慢性 NO 缺乏会导致大鼠脂肪组织质量显著减少。研究还表明，锌离子在调节 NO 功能方面发挥着重要的调节作用。本研究旨在探讨锌离子在 NO 调节的脂肪细胞分化中的作用。我们假设 NO 可以增加细胞内 Zn 水平，然后刺激脂肪细胞分化。使用 ZnCl 和 NO 供体 NONOate 来探讨 Zn 和 NO 对脂肪细胞分化的影响。通过检测来确定 NO 对细胞内 Zn 动员的调节机制。然后，使用 Zn 选择性螯合剂 TPEN 来阐明细胞内 Zn 在 NO 调节的脂肪细胞分化中的作用。此外，还阐明了人皮下脂肪组织中脂肪细胞大小、Zn 水平和 NOS 表达之间的关系。结果表明，ZnCl 和 NO 均以剂量依赖的方式刺激脂肪细胞分化。NO 通过鸟苷酸环化酶（GC）/环磷酸鸟苷（cGMP）/蛋白激酶 G（PKG）途径刺激脂肪细胞内的 Zn 动员，NO 刺激的脂肪细胞分化是 Zn 依赖性的。在人皮下脂肪组织中，脂肪细胞大小与 eNOS 的表达呈负相关。总之，NO 处理通过 GC/cGMP/PKG 途径刺激细胞内 Zn 动员，随后刺激脂肪细胞分化。
