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Regulation of triglyceride metabolism in medaka (Oryzias latipes) hepatocytes by Neu3a sialidase

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Abstract

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, and neu3a mRNA 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.

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Abbreviations

DAG:

diacylglycerol

FFA:

free fatty acid

LacCer:

lactosylceramide

NeuAc:

N-acetylneuraminic acid

TG:

triglyceride

4MU-palmitate:

4- methylumbelliferyl palmitate

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Acknowledgements

We appreciate technical assistances of Shoji Kodama, Asami Ikeda, Wataru Nishimura, and Oki Hayasaka and useful discussions of Prof. Yoshio Kaminishi and Dr. Kiyotaka Fujita.

Funding

This work was supported by JSPS KAKENHI Grant Number 17J06604.

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Correspondence to Kazuhiro Shiozaki.

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Oishi, K., Miyazaki, M., Takase, R. et al. Regulation of triglyceride metabolism in medaka (Oryzias latipes) hepatocytes by Neu3a sialidase. Fish Physiol Biochem 46, 563–574 (2020). https://doi.org/10.1007/s10695-019-00730-6

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  • DOI: https://doi.org/10.1007/s10695-019-00730-6

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