Enhanced insulin activity achieved in VDRa/b ablation zebrafish

Ruolan Liu; Yao Lu; Xuyan Peng; Jingyi Jia; Yonglin Ruan; Shengchi Shi; Tingting Shu; Tianhui Li; Xia Jin; Gang Zhai; Jiangyan He; Qiyong Lou; Zhan Yin

doi:10.3389/fendo.2023.1054665

Enhanced insulin activity achieved in VDRa/b ablation zebrafish

Front Endocrinol (Lausanne). 2023 Feb 13:14:1054665. doi: 10.3389/fendo.2023.1054665. eCollection 2023.

Authors

Ruolan Liu^{1

2}, Yao Lu¹, Xuyan Peng³, Jingyi Jia^{1

2}, Yonglin Ruan^{1

2}, Shengchi Shi^{1

2}, Tingting Shu¹, Tianhui Li¹, Xia Jin¹, Gang Zhai¹, Jiangyan He¹, Qiyong Lou¹, Zhan Yin^{1

2

4}

Affiliations

¹ State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
² College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing, China.
³ The Laboratory of Ophthalmology and Vision Science, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zheng Zhou, China.
⁴ The Innovative Academy of Seed Design, Chinese Academy of Sciences, Beijing, China.

Abstract

Introduction: 1α,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.

Results: In 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.

Discussion: In 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.

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

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Insulin* / metabolism
Lipids
Liver*
Receptors, Calcitriol* / genetics
Signal Transduction
Zebrafish Proteins / genetics
Zebrafish* / genetics

Substances

Insulin
Lipids
Receptors, Calcitriol
Zebrafish Proteins

Grants and funding

This project was supported by the National Key Research and Development Program of China [2022YFF100300]; National Natural Science Foundation, China [32172956 to QL].