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Article

Nitric Oxide Mobilizes Intracellular Zn2+ via the GC/cGMP/PKG Signaling Pathway and Stimulates Adipocyte Differentiation

by 1,†, 2,†, 2, 3,4, 2, 5,6,7, 5,7,8, 9,10,*,‡ and 2,4,11,*,‡
1
College of Human Development and Health, National Taipei University of Nursing and Health Sciences, Taipei 112303, Taiwan
2
Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
3
Institute of Biophotonics, College of Biomedical Science and Engineering, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
4
Department of Medical Research, Taipei Veterans General Hospital, Taipei 112201, Taiwan
5
Institute of Anatomy and Cell Biology, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
6
Department of Critical Care Medicine, Taipei Veterans General Hospital, Taipei 112201, Taiwan
7
Trauma Center, Taipei Veterans General Hospital, Taipei 112201, Taiwan
8
Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 112201, Taiwan
9
Division of Trauma, Department of Surgery, Far-Eastern Memorial Hospital, New Taipei City 220216, Taiwan
10
Graduate Institute of Medicine, Yuan Ze University, Taoyuan 320315, Taiwan
11
Department of Education and Research, Taipei City Hospital, Taipei 103212, Taiwan
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Division of Trauma, Department of Surgery, Far-Eastern Memorial Hospital, No. 21, Sec. 2, Nanya S. Rd., New Taipei City 220216, Taiwan (H.-F.L.). College of Physiology, School of Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Li-Nong St., Taipei 11221, Taiwan (C.-C.J.).
Academic Editors: Didier F. Pisani and Jean-François Tanti
Int. J. Mol. Sci. 2022, 23(10), 5488; https://doi.org/10.3390/ijms23105488
Received: 28 March 2022 / Revised: 3 May 2022 / Accepted: 11 May 2022 / Published: 14 May 2022
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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 Zn2+ level and then stimulate adipocyte differentiation. ZnCl2 and the NO donor, NONOate, were used to explore the effects of Zn2+ and NO on adipocyte differentiation. Regulatory mechanisms of NO on intracellular Zn2+ mobilization were determined by detection. Then, Zn2+-selective chelator TPEN was used to clarify the role of intracellular Zn2+ on NO-regulated adipocyte differentiation. Furthermore, the relationship between adipocyte size, Zn2+ level, and NOS expression in human subcutaneous fat tissue was elucidated. Results showed that both ZnCl2 and NO stimulated adipocyte differentiation in a dose-dependent manner. NO stimulated intracellular Zn2+ mobilization in adipocytes through the guanylate cyclase (GC)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) pathway, and NO-stimulated adipocyte differentiation was Zn2+-dependent. In human subcutaneous adipose tissue, adipocyte size was negatively correlated with expression of eNOS. In conclusion, NO treatment stimulates intracellular Zn2+ mobilization through the GC/cGMP/PKG pathway, subsequently stimulating adipocyte differentiation. View Full-Text
Keywords: zinc; nitric oxide; guanylyl cyclase; protein kinase G; differentiation; adipocyte; obesity zinc; nitric oxide; guanylyl cyclase; protein kinase G; differentiation; adipocyte; obesity
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MDPI and ACS Style

Chen, C.-W.; Chen, L.-K.; Huang, T.-Y.; Yang, D.-M.; Liu, S.-Y.; Tsai, P.-J.; Chen, T.-H.; Lin, H.-F.; Juan, C.-C. Nitric Oxide Mobilizes Intracellular Zn2+ via the GC/cGMP/PKG Signaling Pathway and Stimulates Adipocyte Differentiation. Int. J. Mol. Sci. 2022, 23, 5488. https://doi.org/10.3390/ijms23105488

AMA Style

Chen C-W, Chen L-K, Huang T-Y, Yang D-M, Liu S-Y, Tsai P-J, Chen T-H, Lin H-F, Juan C-C. Nitric Oxide Mobilizes Intracellular Zn2+ via the GC/cGMP/PKG Signaling Pathway and Stimulates Adipocyte Differentiation. International Journal of Molecular Sciences. 2022; 23(10):5488. https://doi.org/10.3390/ijms23105488

Chicago/Turabian Style

Chen, Chien-Wei, Luen-Kui Chen, Tai-Ying Huang, De-Ming Yang, Shui-Yu Liu, Pei-Jiun Tsai, Tien-Hua Chen, Heng-Fu Lin, and Chi-Chang Juan. 2022. "Nitric Oxide Mobilizes Intracellular Zn2+ via the GC/cGMP/PKG Signaling Pathway and Stimulates Adipocyte Differentiation" International Journal of Molecular Sciences 23, no. 10: 5488. https://doi.org/10.3390/ijms23105488

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