Fatty Acid Oxidation in Zebrafish Adipose Tissue Is Promoted by 1α,25(OH)2D3

Publication date: 16 May 2017
Source:Cell Reports, Volume 19, Issue 7
Author(s): Xuyan Peng, Guohui Shang, Wenqing Wang, Xiaowen Chen, Qiyong Lou, Gang Zhai, Dongliang Li, Zhenyu Du, Yali Ye, Xia Jin, Jiangyan He, Yi Zhang, Zhan Yin
1α,25(OH)2D3 (vitamin D3) is crucial for mineral homeostasis in mammals, but the precise effects of 1α,25(OH)2D3 in adipose tissue remain to be clarified in vivo. The initial 25-hydroxylation is catalyzed by liver microsomal cytochrome P450 2R1 (CYP2R1), which is conserved in vertebrates. To probe the physiological function(s) of 1α,25(OH)2D3 in teleosts, we generated two independent cyp2r1-deficient zebrafish lines. These mutants exhibit retarded growth and increased obesity, especially in the visceral adipose tissue (VAT). These defects could be rescued with 25(OH)D3 treatments. ChIP-PCR analyses demonstrated that pgc1a is the target of the vitamin D receptor in the liver and VAT of zebrafish. Significantly decreased protein levels of Pgc1a, impaired mitochondrial biogenesis, and free fatty acid oxidation are also observed in the cyp2r1 mutant VAT. Our results demonstrate that regulation of 1α,25(OH)2D3 during lipid metabolism occurs through the regulation of Pgc1a for mitochondrial biogenesis and oxidative metabolism within zebrafish VAT.

Graphical abstract

Teaser

Peng et al. find that Cyp2r1 depletion results in 1,25(OH)2D3 deficiency, retarded growth, and excessive visceral adipose tissue (VAT) in zebrafish. 1,25(OH)2D3 regulates lipid metabolism through the regulation of Pgc1a, controlling mitochondrial biogenesis and oxidative metabolism in zebrafish VAT.


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