PUBLICATION

Androgen signaling inhibits de novo lipogenesis to alleviate lipid deposition in zebrafish

Authors
Jia, J.Y., Chen, G.H., Shu, T.T., Lou, Q.Y., Jin, X., He, J.Y., Xiao, W.H., Zhai, G., Yin, Z.
ID
ZDB-PUB-240315-5
Date
2024
Source
Zoological research   45: 355366355-366 (Journal)
Registered Authors
Xiao, Wuhan, Yin, Zhan
Keywords
Androgen receptor, Cyp17a1, De novo lipogenesis, Fatty acid synthesis, Testosterone
MeSH Terms
  • Androgens*/pharmacology
  • Animals
  • Chromatin
  • Lipids
  • Lipogenesis*/genetics
  • Male
  • Signal Transduction
  • Testosterone
  • Zebrafish/genetics
(all 9)
PubMed
38485505 Full text @ Zool Res
Abstract
Testosterone is closely associated with lipid metabolism and known to affect body fat composition and muscle mass in males. However, the mechanisms by which testosterone acts on lipid metabolism are not yet fully understood, especially in teleosts. In this study, cyp17a1-/- zebrafish ( Danio rerio) exhibited excessive visceral adipose tissue (VAT), lipid content, and up-regulated expression and activity of hepatic de novo lipogenesis (DNL) enzymes. The assay for transposase accessible chromatin with sequencing (ATAC-seq) results demonstrated that chromatin accessibility of DNL genes was increased in cyp17a1-/- fish compared to cyp17a1+/+ male fish, including stearoyl-CoA desaturase ( scd) and fatty acid synthase ( fasn). Androgen response element (ARE) motifs in the androgen signaling pathway were significantly enriched in cyp17a1+/+ male fish but not in cyp17a1-/- fish. Both androgen receptor ( ar)-/- and wild-type (WT) zebrafish administered with Ar antagonist flutamide displayed excessive visceral adipose tissue, lipid content, and up-regulated expression and activity of hepatic de novo lipogenesis enzymes. The Ar agonist BMS-564929 reduced the content of VAT and lipid content, and down-regulated acetyl-CoA carboxylase a ( acaca), fasn, and scd expression. Mechanistically, the rescue effect of testosterone on cyp17a1-/- fish in terms of phenotypes was abolished when ar was additionally depleted. Collectively, these findings reveal that testosterone inhibits lipid deposition by down-regulating DNL genes via Ar in zebrafish, thus expanding our understanding of the relationship between testosterone and lipid metabolism in teleosts.
Genes / Markers
Figures
Figure Gallery (6 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ihb144
    		Small Deletion
    ihb1226
      		Small Deletion
      1 - 2 of 2
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      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      Target Reagent Reagent Type
      cyp17a1TALEN1-cyp17a1TALEN
      1 - 1 of 1
      Show
      Fish
      No data available
      Antibodies
      No data available
      Orthology
      No data available
      Engineered Foreign Genes
      No data available
      Mapping
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      Citation
      Jia, J.Y., Chen, G.H., Shu, T.T., Lou, Q.Y., Jin, X., He, J.Y., Xiao, W.H., Zhai, G., Yin, Z. (2024) Androgen signaling inhibits de novo lipogenesis to alleviate lipid deposition in zebrafish. Zoological research. 45:355366355-366.