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

作　　者：Jing-Yi Jia Guang-Hui Chen Ting-Ting Shu Qi-Yong Lou Xia Jin Jiang-Yan He Wu-Han Xiao Gang Zhai Zhan Yin 

机构地区：[1]College of Fisheries,Huazhong Agriculture University,Wuhan,Hubei 430070,China [2]State Key Laboratory of Freshwater Ecology and Biotechnology,Institute of Hydrobiology,Chinese Academy of Sciences,Wuhan,Hubei 430072,China [3]College of Advanced Agricultural Sciences,University of Chinese Academy of Sciences,Beijing 100049,China [4]Hubei Key Laboratory of Three Gorges Project for Conservation of Fishes,Chinese Sturgeon Research Institute,China Three Gorges Corporation,Yichang,Hubei 443100,China [5]Hubei Hongshan Laboratory,Huazhong Agriculture University,Wuhan,Hubei 430070,China [6]Innovative Academy of Seed Design,Chinese Academy of Sciences,Beijing 100049,China

出　　处：《Zoological Research》2024年第2期355-366,共12页动物学研究（英文）

基　　金：supported by the National Key Research and Development Program,China (2022YFF1000300 to Z.Y.and2022YFD2401800 to G.Z.);Pilot Program A Project from the Chinese Academy of Sciences (XDA24010206 to Z.Y.);Foundation of Hubei Hongshan Laboratory (2021hskf013 to G.Z.and 2021hszd021 to Z.Y.);National Natural Science Foundation of China (31972779 to G.Z.);Youth Innovation Promotion Association of CAS (2020336 to G.Z.);State Key Laboratory of Freshwater Ecology and Biotechnology (2016FBZ05 to Z.Y.)。

摘　　要：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 chromatinwithsequencing(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 wildtype(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.

关 键 词：Cyp17a1 TESTOSTERONE Androgen receptor De novo lipogenesis Fatty acid synthesis 

分 类 号：S917.4[农业科学—水产科学]