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Hif1 & alpha;/Dhrs3a Pathway Participates in Lipid Droplet Accumulation via Retinol and Ppar-& gamma; in Fish Hepatocytes

文献类型： 外文期刊

作者： Tian, Jingjing 1 ; Du, Yihui 1 ; Wang, Binbin 1 ; Ji, Mengmeng 1 ; Li, Hongyan 1 ; Xia, Yun 1 ; Zhang, Kai 1 ; Li, Zhifei 1 ; Xie, Wenping 1 ; Gong, Wangbao 1 ; Yu, Ermeng 1 ; Wang, Guangjun 1 ; Xie, Jun 1 ;

作者机构： 1.Chinese Acad Fishery Sci, Pearl River Fisheries Res Inst, Key Lab Aquat Anim Immune Technol Guangdong Prov, Guangzhou 510380, Peoples R China

2.Chinese Acad Fishery Sci, Pearl River Fisheries Res Inst, Key Lab Trop & Subtrop Fishery Resource Applicat &, Guangzhou 510380, Peoples R China

3.Chinese Acad Fishery Sci, Hainan Fisheries Innovat Res Inst, Sanya 572024, Peoples R China

关键词： aquaculture; fatty liver; fatty acid; hypoxia; cell culture; lipid droplet; lipoprotein; liver; retinoids

期刊名称：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES （ 影响因子：5.6； 五年影响因子：6.2 ）

ISSN： 1661-6596

年卷期： 2023 年 24 卷 12 期

页码：

收录情况： SCI

摘要： Excessive hepatic lipid accumulation is a common phenomenon in cultured fish; however, its underlying mechanisms are poorly understood. Lipid droplet (LD)-related proteins play vital roles in LD accumulation. Herein, using a zebrafish liver cell line (ZFL), we show that LD accumulation is accompanied by differential expression of seven LD-annotated genes, among which the expression of dehydrogenase/reductase (SDR family) member 3 a/b (dhrs3a/b) increased synchronously. RNAi-mediated knockdown of dhrs3a delayed LD accumulation and downregulated the mRNA expression of peroxisome proliferator-activated receptor gamma (pparg) in cells incubated with fatty acids. Notably, Dhrs3 catalyzed retinene to retinol, the content of which increased in LD-enriched cells. The addition of exogenous retinyl acetate maintained LD accumulation only in cells incubated in a lipid-rich medium. Correspondingly, exogenous retinyl acetate significantly increased pparg mRNA expression levels and altered the lipidome of the cells by increasing the phosphatidylcholine and triacylglycerol contents and decreasing the cardiolipin, phosphatidylinositol, and phosphatidylserine contents. Administration of LW6, an hypoxia-inducible factor 1 & alpha; (HIF1 & alpha;) inhibitor, reduced the size and number of LDs in ZFL cells and attenuated hif1 & alpha;a, hif1 & alpha;b, dhrs3a, and pparg mRNA expression levels. We propose that the Hif-1 & alpha;/Dhrs3a pathway participates in LD accumulation in hepatocytes, which induces retinol formation and the Ppar-& gamma; pathway.

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