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

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外文摘要：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.

外文关键词：

ZebrafishscdLiverLipid homeostasisReproduction

作者：

Shan-Shan Xu、Yi Li、Hou-Peng Wang、Wen-Bo Chen、Ya-Qing Wang、Zi-Wei Song、Hui Liu、Shan Zhong、Yong-Hua Sun

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作者单位：

Department of Genetics,Wuhan University School of Basic Medical Sciences,Wuhan,Hubei 430071,China

State Key Laboratory of Freshwater Ecology and Biotechnology,Hubei Hongshan Laboratory,Institute of Hydrobiology,Innovation Academy for Seed Design(INASEED),Chinese Academy of Sciences,Wuhan,Hubei 430072,China

Hubei Province Key Laboratory of Allergy and Immunology,Wuhan,Hubei 430071,China

College of Advanced Agricultural Sciences,University of Chinese Academy of Sciences,Beijing 100049,China

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基金：

中国科学院战略规划重点项目国家自然科学基金国家自然科学基金Project from the State Key Laboratory of Freshwater Ecology and Biotechnology

项目编号：

XDA2401010831872554321729522019FBZ05

出版年：

2023

DOI：

10.24272/j.issn.2095-8137.2022.167

动物学研究