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Sexual dimorphism in zebrafish liver proteins and implications for hepatic regeneration and diseases

Niksirat, Hamid ; Mengal, Kifayatullah ; Kor, Golara ; Steinbach, Christoph and Levander, Fredrik LU orcid (2025) In Scientific Reports 15(1).
Abstract

The liver is a central metabolic hub, performing vital functions such as bile production, protein, carbohydrate, lipid and drug metabolism, detoxification of xenobiotics, and the synthesis of essential biomolecules for reproduction, and also shows regenerative capability. Several of these functions can be affected by sexual dimorphisms with important consequences. In this study we used high-throughput proteomics to identify and quantify proteins involved in sexual dimorphism of the zebrafish liver, as a model for preclinical human research. Additionally, we conducted an extensive literature review to explore potential effects of sex-biased protein abundances on liver regeneration capacity and hepatic diseases. The results showed... (More)

The liver is a central metabolic hub, performing vital functions such as bile production, protein, carbohydrate, lipid and drug metabolism, detoxification of xenobiotics, and the synthesis of essential biomolecules for reproduction, and also shows regenerative capability. Several of these functions can be affected by sexual dimorphisms with important consequences. In this study we used high-throughput proteomics to identify and quantify proteins involved in sexual dimorphism of the zebrafish liver, as a model for preclinical human research. Additionally, we conducted an extensive literature review to explore potential effects of sex-biased protein abundances on liver regeneration capacity and hepatic diseases. The results showed wide-spread sex-specific differences in proteins involved in carbohydrate, protein, and lipid metabolism. Female livers exhibited higher levels of proteins involved in protein synthesis, while male liver protein abundances were higher in energy-producing biochemical pathways, such as the TCA, β-oxidation, and glycolysis. Furthermore, significant sex differences were observed in proteins related to drug metabolism, which should be considered in toxicological and pharmacological research. Some potential links between sex-biased quantities of some key hepatic proteins and the susceptibility of males to liver diseases, as well as the higher hepatic regenerative capacity in females, were suggested. These findings offer a foundation for future targeted research to facilitate the development of sex-specific therapeutic approaches for liver disorders and regenerative medicine. Data are available via ProteomeXchange with identifier PXD061886.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Drug metabolism, Liver disease, Liver proteomics, Metabolism, Sexual dimorphism, Zebrafish model
in
Scientific Reports
volume
15
issue
1
article number
33565
publisher
Nature Publishing Group
external identifiers
  • scopus:105017738928
  • pmid:41023193
ISSN
2045-2322
DOI
10.1038/s41598-025-18599-2
language
English
LU publication?
yes
id
91ea491d-53ab-4442-82cc-4bcb4a15e8b4
date added to LUP
2025-11-21 12:20:53
date last changed
2025-11-22 03:00:09
@article{91ea491d-53ab-4442-82cc-4bcb4a15e8b4,
  abstract     = {{<p>The liver is a central metabolic hub, performing vital functions such as bile production, protein, carbohydrate, lipid and drug metabolism, detoxification of xenobiotics, and the synthesis of essential biomolecules for reproduction, and also shows regenerative capability. Several of these functions can be affected by sexual dimorphisms with important consequences. In this study we used high-throughput proteomics to identify and quantify proteins involved in sexual dimorphism of the zebrafish liver, as a model for preclinical human research. Additionally, we conducted an extensive literature review to explore potential effects of sex-biased protein abundances on liver regeneration capacity and hepatic diseases. The results showed wide-spread sex-specific differences in proteins involved in carbohydrate, protein, and lipid metabolism. Female livers exhibited higher levels of proteins involved in protein synthesis, while male liver protein abundances were higher in energy-producing biochemical pathways, such as the TCA, β-oxidation, and glycolysis. Furthermore, significant sex differences were observed in proteins related to drug metabolism, which should be considered in toxicological and pharmacological research. Some potential links between sex-biased quantities of some key hepatic proteins and the susceptibility of males to liver diseases, as well as the higher hepatic regenerative capacity in females, were suggested. These findings offer a foundation for future targeted research to facilitate the development of sex-specific therapeutic approaches for liver disorders and regenerative medicine. Data are available via ProteomeXchange with identifier PXD061886.</p>}},
  author       = {{Niksirat, Hamid and Mengal, Kifayatullah and Kor, Golara and Steinbach, Christoph and Levander, Fredrik}},
  issn         = {{2045-2322}},
  keywords     = {{Drug metabolism; Liver disease; Liver proteomics; Metabolism; Sexual dimorphism; Zebrafish model}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Sexual dimorphism in zebrafish liver proteins and implications for hepatic regeneration and diseases}},
  url          = {{http://dx.doi.org/10.1038/s41598-025-18599-2}},
  doi          = {{10.1038/s41598-025-18599-2}},
  volume       = {{15}},
  year         = {{2025}},
}