Enhanced insulin activity achieved in VDRa/b ablation zebrafish

Frontiers in Endocrinology

Endocrinology

Tingting Shu¹  Xia Jin¹  Gang Zhai¹  Jiangyan He¹  Yao Lu¹  Tianhui Li¹  Qiyong Lou¹  Ruolan Liu²  Shengchi Shi²  Yonglin Ruan²  Jingyi Jia²  Zhan Yin³  Xuyan Peng⁴ 

[1] State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China;State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China;College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing, China;State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China;College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing, China;The Innovative Academy of Seed Design, Chinese Academy of Sciences, Beijing, China;The Laboratory of Ophthalmology and Vision Science, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zheng Zhou, China;

关键词: 1α,25(OH)2VD3;    VDRs;    insulin;    lipolysis;    glucose metabolism;   

DOI  :  10.3389/fendo.2023.1054665

 received in 2022-09-27, accepted in 2023-01-30,  发布年份 2023

来源: Frontiers

【 摘 要 】

Introduction1α,25-dihydroxyvitamin D3 (1α,25[OH]2VD3) is a hormone known for its key roles in calcium absorption and nutrient metabolism. In teleost fishes, 1α,25(OH)2VD3 insufficiency causes impaired glucose metabolism and lipid oxidation. However, the cascade and mechanisms of 1α,25(OH)2VD3 and the vitamin d receptor (VDR) signaling are unclear.ResultsIn this study, two genes (vdra and vdrb) encoding paralogs of VDRs were genetically knocked out in zebrafish. Growth retardation and accumulated visceral adipose tissue have been observed in vdra-/-;vdrb-/- deficient line. In the liver elevated accumulation of triglycerides and suppressed lipid oxidation were detected. Morover significantly elevated 1α,25(OH)2VD3 levels were detected in vdra-/-;vdrb-/- zebrafish due to cyp24a1 transcription repression. Furthermore VDRs ablation Enhanced insulin signaling including elevated insulin/insra trancriptional levels, glycolysis, lipogenesis and promoted AKT/mTOR activity.DiscussionIn conclusion, our present studies provides a zebrafish model with an elevated 1α,25(OH)2VD3 levels in vivo. The 1α,25(OH)2VD3/VDRs signaling promote lipid oxidation activity. However 1α,25(OH)2VD3 activity of regulation of glucose homeostasis through Insulin/Insr was independent of nuclear VDRs in teleosts.

【 授权许可】

Unknown   
Copyright © 2023 Liu, Lu, Peng, Jia, Ruan, Shi, Shu, Li, Jin, Zhai, He, Lou and Yin