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
- PubMed
- 38485505 Full text @ Zool Res
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.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping