Enhanced insulin activity achieved in VDRa/b ablation zebrafish

• Published in: Frontiers in endocrinology (Lausanne) Vol. 14; p. 1054665
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 13.02.2023
• Subjects: 1α,25(OH)2VD3; Animals; Endocrinology; glucose metabolism; insulin; Insulin - metabolism; Lipids; lipolysis; Liver; Receptors, Calcitriol - genetics; Signal Transduction; VDRs; Zebrafish - genetics; Zebrafish Proteins - genetics; 1α,25(OH)2VD3; insulin; lipolysis; glucose metabolism; VDRs
• ISSN: 1664-2392; 1664-2392
• DOI: 10.3389/fendo.2023.1054665

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