Prostaglandin 2 alpha Promotes Autophagy and Mitochondrial Energy Production in Fish Hepatocytes

文献类型： 外文期刊

第一作者： Tian, Jingjing

作者： Tian, Jingjing;Du, Yihui;Yu, Ermeng;Lei, Caixia;Xia, Yun;Jiang, Peng;Li, Hongyan;Zhang, Kai;Li, Zhifei;Gong, Wangbao;Xie, Jun;Wang, Guangjun;Tian, Jingjing;Du, Yihui;Yu, Ermeng;Lei, Caixia;Xia, Yun;Jiang, Peng;Li, Hongyan;Zhang, Kai;Li, Zhifei;Gong, Wangbao;Xie, Jun;Wang, Guangjun

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关键词： arachidonic acid; ATP; cyclooxygenase; eicosanoids; lipid droplets; lipolysis; lipophagy; mitochondria; PGF2 alpha

期刊名称：CELLS （ 影响因子：7.666； 五年影响因子：7.677 ）

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年卷期： 2022 年 11 卷 12 期

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收录情况： SCI

摘要： Fatty liver, characterized by excessive lipid droplet (LD) accumulation in hepatocytes, is a common physiological condition in humans and aquaculture species. Lipid mobilization is an important strategy for modulating the number and size of cellular LDs. Cyclooxygenase (COX)-mediated arachidonic acid derivatives are known to improve lipid catabolism in fish; however, the specific derivatives remain unknown. In the present study, we showed that serum starvation induced LD degradation via autophagy, lipolysis, and mitochondrial energy production in zebrafish hepatocytes, accompanied by activation of the COX pathway. The cellular concentration of PGF2 alpha, but not other prostaglandins, was significantly increased. Administration of a COX inhibitor or interference with PGF2 alpha synthase abolished serum deprivation-induced LD suppression, LD-lysosome colocalization, and expression of autophagic genes. Additionally, exogenous PGF2 alpha suppressed the accumulation of LDs, promoted the accumulation of lysosomes with LD and the autophagy marker protein LC3A/B, and augmented the expression of autophagic genes. Moreover, PGF2 alpha enhanced mitochondrial accumulation and ATP production, and increased the transcript levels of beta-oxidation- and mitochondrial respiratory chain-related genes. Collectively, these findings demonstrate that the COX pathway is implicated in lipid degradation induced by energy deprivation, and that PGF2 alpha is a key molecule triggering autophagy, lipolysis, and mitochondrial development in zebrafish hepatocytes.

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