Research
| Title： | Enhanced insulin activity achieved in VDRa/b ablation zebrafish |
|---|---|
| First 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 |
| Journal： | FRONTIERS IN ENDOCRINOLOGY |
| Years： | 2023 |
| DOI： | 10.3389/fendo.2023.1054665 |
| Abstract： | Introduction: 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25[OH](2)VD3) is a hormone known for its key roles in calcium absorption and nutrient metabolism. In teleost fishes, 1 alpha,25(OH)(2)VD3 insufficiency causes impaired glucose metabolism and lipid oxidation. However, the cascade and mechanisms of 1 alpha,25(OH)(2)VD3 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 1 alpha,25(OH)(2)VD3 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 1 alpha,25(OH)(2)VD3 levels in vivo. The 1 alpha,25(OH)(2)VD3/VDRs signaling promote lipid oxidation activity. However 1 alpha,25(OH)(2)VD3 activity of regulation of glucose homeostasis through Insulin/Insr was independent of nuclear VDRs in teleosts. |
