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Shan-Shan Xu, Yi Li, Hou-Peng Wang, Wen-Bo Chen, Ya-Qing Wang, Zi-Wei Song, Hui Liu, Shan Zhong, Yong-Hua Sun. Depletion of stearoyl-CoA desaturase (scd) leads to fatty liver disease and defective mating behavior in zebrafish. Zoological Research, 2023, 44(1): 63-77. doi: 10.24272/j.issn.2095-8137.2022.167
Citation: Shan-Shan Xu, Yi Li, Hou-Peng Wang, Wen-Bo Chen, Ya-Qing Wang, Zi-Wei Song, Hui Liu, Shan Zhong, Yong-Hua Sun. Depletion of stearoyl-CoA desaturase (scd) leads to fatty liver disease and defective mating behavior in zebrafish. Zoological Research, 2023, 44(1): 63-77. doi: 10.24272/j.issn.2095-8137.2022.167

Depletion of stearoyl-CoA desaturase (scd) leads to fatty liver disease and defective mating behavior in zebrafish

doi: 10.24272/j.issn.2095-8137.2022.167
The genomic and transcriptomic data were submitted to the NCBI GEO database under accession number GSE207660, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE207660, GSA database under accession number CRA008031 (https://ngdc.cncb.ac.cn/gsa/), and Science Data Bank under doi:10.57760/sciencedb.j00139.00036. (https://www.scidb.cn/en)
Supplementary data to this article can be found online.
The authors declare that they have no competing interests.
Y.H.S. conceived and designed the study. S.Z. and Y.H.S. supervised the analyses. S.S.X., Y.L., H.P.W., and Y.Q.W. prepared the data. W.B.C. performed RNA-seq analysis. S.S.X. and Y.H.S. analyzed the data. S.S.X., Z.W.S., and H.L. prepared the draft of the manuscript. S.S.X. and Y.H.S. revised and finalized the manuscript. All authors read and approved the final version of the manuscript.
Funds:  This study was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA24010108), National Natural Science Foundation of China (31872554, 32172952), and Project from the State Key Laboratory of Freshwater Ecology and Biotechnology (2019FBZ05)
More Information
  • Stearyl coenzyme A desaturase (SCD), also known as delta-9 desaturase, catalyzes the rate-limiting step in the formation of monounsaturated fatty acids. In mammals, depletion or inhibition of SCD activity generally leads to a decrease in triglycerides and cholesteryl esters. However, the endogenous role of scd in teleost fish remains unknown. Here, we generated a zebrafish scd mutant (scd-/-) to elucidate the role of scd in lipid metabolism and sexual development. Gas chromatography-mass spectrometry (GC-MS) showed that the scd -/- mutants had increased levels of saturated fatty acids C16:0 and C18:0, and decreased levels of monounsaturated fatty acids C16:1 and C18:1. The mutant fish displayed a short stature and an enlarged abdomen during development. Unlike Scd-/- mammals, the scd-/- zebrafish showed significantly increased fat accumulation in the whole body, especially in the liver, leading to hepatic mitochondrial dysfunction and severe cell apoptosis. Mechanistically, srebf1, a gene encoding a transcriptional activator related to adipogenesis, acc1 and acaca, genes involved in fatty acid synthesis, and dgat2, a key gene involved in triglyceride synthesis, were significantly upregulated in mutant livers to activate fatty acid biosynthesis and adipogenesis. The scd-/- males exhibited defective natural mating behavior due to defective genital papillae but possessed functional mature sperm. All defects in the scd-/- mutants could be rescued by ubiquitous transgenic overexpression of scd. In conclusion, our study demonstrates that scd is indispensable for maintaining lipid homeostasis and development of secondary sexual characteristics in zebrafish.
  • The genomic and transcriptomic data were submitted to the NCBI GEO database under accession number GSE207660, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE207660, GSA database under accession number CRA008031 (https://ngdc.cncb.ac.cn/gsa/), and Science Data Bank under doi:10.57760/sciencedb.j00139.00036. (https://www.scidb.cn/en)
    Supplementary data to this article can be found online.
    The authors declare that they have no competing interests.
    Y.H.S. conceived and designed the study. S.Z. and Y.H.S. supervised the analyses. S.S.X., Y.L., H.P.W., and Y.Q.W. prepared the data. W.B.C. performed RNA-seq analysis. S.S.X. and Y.H.S. analyzed the data. S.S.X., Z.W.S., and H.L. prepared the draft of the manuscript. S.S.X. and Y.H.S. revised and finalized the manuscript. All authors read and approved the final version of the manuscript.
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