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Enhanced insulin activity achieved in VDRa/b ablation zebrafish
Ruolan Liu1,2, Yao Lu1, Xuyan Peng3
1State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
Frontiers in Endocrinology
|March 3, 2023
Summary
Vitamin D hormone (1α,25[OH]2VD3) signaling via vitamin D receptors (VDRs) promotes lipid oxidation in zebrafish. However, glucose homeostasis regulation by 1α,25(OH)2VD3 is independent of nuclear VDRs in teleosts.
Area of Science:
- Endocrinology
- Molecular Biology
- Zebrafish Models
Background:
- 1α,25-dihydroxyvitamin D3 (1α,25[OH]2VD3) is crucial for calcium and nutrient metabolism.
- In teleost fish, vitamin D insufficiency impairs glucose and lipid metabolism, but mechanisms remain unclear.
Purpose of the Study:
- To investigate the roles of vitamin D receptor (VDR) paralogs (Vdra and Vdrb) in zebrafish.
- To elucidate the signaling pathways of 1α,25(OH)2VD3 in lipid and glucose metabolism.
Main Methods:
- Genetic knockout of *vdra* and *vdrb* genes in zebrafish.
- Analysis of growth, visceral adipose tissue, liver triglycerides, and lipid oxidation.
- Measurement of 1α,25(OH)2VD3 levels and gene expression related to insulin signaling and AKT/mTOR pathway.
Main Results:
- *vdra*-/-;*vdrb*-/- zebrafish exhibited growth retardation and visceral fat accumulation.
- Liver showed increased triglycerides and suppressed lipid oxidation.
- VDR ablation led to elevated 1α,25(OH)2VD3, enhanced insulin signaling, glycolysis, lipogenesis, and AKT/mTOR activity.
Conclusions:
- Zebrafish VDRs (Vdra and Vdrb) are essential for regulating lipid oxidation via 1α,25(OH)2VD3 signaling.
- 1α,25(OH)2VD3's regulation of glucose homeostasis through Insulin/Insr is independent of nuclear VDRs in teleosts.
