Enhanced insulin activity achieved in VDRa/b ablation zebrafish

VDRa/b 消融斑马鱼的胰岛素活性增强

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作者: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

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.

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.

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