Regulation of triglyceride metabolism in medaka (Oryzias latipes) hepatocytes by Neu3a sialidase
Regulation of triglyceride metabolism in medaka (Oryzias latipes) hepatocytes by Neu3a sialidase
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DOI：
10.1007/s10695-019-00730-6
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发表时间：
2019-12
影响因子：
2.9
通讯作者：
Kazuki Oishi;M. Miyazaki;Ryo Takase;P. Chigwechokha;M. Komatsu;K. Shiozaki
中科院分区：
文献类型：
--
作者：
Kazuki Oishi;M. Miyazaki;Ryo Takase;P. Chigwechokha;M. Komatsu;K. Shiozaki
鱼类将甘油三酯（TGs）储存在肝脏、肌肉和脂肪组织中，并在代谢需求时构成能量来源。肝脏通常在脂质代谢中起重要作用。最近的研究表明，神经节苷脂可能调节哺乳动物的肝脏脂质代谢；然而，神经节苷脂介导的鱼类脂质代谢调控尚不清楚。本研究旨在阐明神经节苷脂在鱼类TG代谢中的作用，特别是在鱼肝脏中表达的神经节苷脂特异性唾液酸酶Neu3a。禁食条件下，medaka肝脏TG含量降低，neu3amrna水平显著上调。为了确定Neu3a在肝脏脂质代谢中的作用，我们利用鱼肝脏Hepa-T1细胞制备了Neu3a稳定的转染物。用油酸处理Neu3a细胞后，与模拟细胞相比，检测到TG的减少。此外，Neu3a细胞的脂肪酶活性高于模拟细胞。为了检验是哪种神经节苷脂调节了这些事件，我们分析了Neu3a细胞中神经节苷脂组成的变化。Neu3a细胞表现出乳糖神经酰胺（LacCer）水平升高，这是一种源于GM3的Neu3酶产物。此外，LacCer暴露于Hepa-T1细胞导致中性脂肪酶活性增加。目前的研究结果表明，在禁食条件下，medaka中Neu3a的上调加速了肝脏TG降解，通过GM3脱氮化产生能量。
Fish store triglycerides (TGs) in the liver, muscle, and adipose tissue and TGs constitute an energy source upon metabolic demand. The liver generally plays important roles in lipid metabolism. Recent studies have suggested the possibility of hepatic lipid metabolic regulation by ganglioside in mammals; however, ganglioside-mediated regulation of lipid metabolism is unclear in fish. This study aimed to clarify the role of ganglioside in fish TG metabolism, with particular reference to Neu3a, a ganglioside-specific sialidase expressed in the fish liver. Under fasting conditions, there was a decrease in hepatic TG contents, andneu3amRNA level was significantly up-regulated in the medaka liver. To determine the role of Neu3a in hepatic lipid metabolism, Neu3a stable transfectants were generated using fish liver Hepa-T1 cells. After treating Neu3a cells with oleic acid, reduction of TG was detected in comparison with the mock cells. Furthermore, lipase activity was greater in Neu3a cells than in mock cells. To examine which ganglioside regulates these events, alterations of ganglioside composition in Neu3a cells were analyzed. Neu3a cells exhibited increased level of lactosylceramide (LacCer), a Neu3 enzymatic product originating from GM3. In addition, exposure of LacCer toward Hepa-T1 cells resulted in an increase of neutral lipase activity. The present results suggest that Neu3a up-regulation in medaka under fasting condition accelerates hepatic TG degradation for energy production via GM3 desialylation.