Fatty Acid Oxidation in Zebrafish Adipose Tissue Is Promoted by 1α,25(OH) 2 D 3

Cell Rep. 2017 May 16;19(7):1444-1455. doi: 10.1016/j.celrep.2017.04.066.

Abstract

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.

Keywords: adipose tissue; cyp2r1 depletion; lipid oxidation; vitamin D(3); zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism*
  • Animals
  • Calcifediol / pharmacology*
  • Cytochrome P450 Family 2 / metabolism
  • Fatty Acids / metabolism*
  • Gene Deletion
  • Gene Targeting
  • Lipolysis / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mutation / genetics
  • Oxidation-Reduction / drug effects
  • Promoter Regions, Genetic / genetics
  • Receptors, Calcitriol / metabolism
  • Zebrafish / genetics
  • Zebrafish / growth & development
  • Zebrafish / metabolism*
  • Zebrafish Proteins / metabolism

Substances

  • Fatty Acids
  • Receptors, Calcitriol
  • Zebrafish Proteins
  • Cytochrome P450 Family 2
  • Calcifediol