Introduction

AUTHOR=Liu Ruolan , Lu Yao , Peng Xuyan , Jia Jingyi , Ruan Yonglin , Shi Shengchi , Shu Tingting , Li Tianhui , Jin Xia , Zhai Gang , He Jiangyan , Lou Qiyong , Yin Zhan TITLE=Enhanced insulin activity achieved in VDRa/b ablation zebrafish JOURNAL=Frontiers in Endocrinology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1054665 DOI=10.3389/fendo.2023.1054665 ISSN=1664-2392 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.