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.
Similar content being viewed by others
Abbreviations
- DAG:
-
diacylglycerol
- FFA:
-
free fatty acid
- LacCer:
-
lactosylceramide
- NeuAc:
-
N-acetylneuraminic acid
- TG:
-
triglyceride
- 4MU-palmitate:
-
4- methylumbelliferyl palmitate
References
Ando S, Mori Y (1993) Characteristics of serum lipoprotein features associated with lipid levels of muscle and liver from five species of fish. Nippon Suisan Gakkaishi 59:1565–1571. https://doi.org/10.2331/suisan.59.1565
Bergan HE, Kittilson JD, Sheridan MA (2012) Nutrition-regulated lipolysis in rainbow trout (Oncorhynchus mykiss) is associated with alteration in the ERK, PI3K-Akt, JAK-STAT, and PKC signaling pathways. Gen Comp Endorinol 176:367–376. https://doi.org/10.1016/j.ygcen.2011.12.013
Chigwechokha PK, Komatsu M, Itakura T, Shiozaki K (2014) Nile Tilapia Neu3 sialidases: Molecular cloning, functional characterization and expression in Oreochromis niloticus. Gene 552:155–164. https://doi.org/10.1016/j.gene.2014.09.029
Chigwechokha PK, Tabata M, Shinyoshi S, Oishi K, Araki K, Komatsu M, Itakura T, Shiozaki K (2015) Recombinant sialidase NanA (rNanA) cleaves α2-3 linked sialic acid of host cell surface N-linked glycoprotein to promote Edwardsiella tarda infection. Fish Shellfish Immun 47:34–45. https://doi.org/10.1016/j.fsi.2015.08.015
Choi H, Jin U, Kang S, Abekura F, Park J, Kwon K, Suh S, Cho S, Ha K, Lee Y, Chung T, Kim C (2017) Monosialyl ganglioside GM3 decreases apolipoprotein B-100 secretion in liver cells. J Cell Biochem 118:2168–2181. https://doi.org/10.1002/jcb.25860
Colins AL, Anderson TA (1995) The regulation of endogeneous energy stores during starvation and refeeding in the somatic tissues of the golden perch. J Fish Biol 47:1004–1015. https://doi.org/10.1111/j.1095-8649.1995.tb06024.x
Freysz L, Farooqui AA, Horrocks LA, Massarelli R, Dreyfus H (1991) Stimulation of mono- and diacylglycerol lipase activities by gangliosides in chicken neuronal cultures. Neurochem Res 16:1241–1244. https://doi.org/10.1007/BF00966702
Garner B, Priestman DA, Stocker R, Harvey DJ, Butters TD, Platt FM (2002) Increased glycosphingolipid levels in serum and aortae of apolipoprotein E gene knockout mice. J Lipid Res 43:205–214
Hakomori S, Igarashi Y (1995) Functional role of glycosphingolipids in cell recognition and signaling. J Biochem 118:1091–1103. https://doi.org/10.1093/oxfordjournals.jbchem.a124992
Hakomori S, Yamamura S, Handa K (1998) Signal transduction through glycol(sphingo)lipids: Introduction and recent studies on glyco(sphingo)lipid-enriched microdomains. Ann N Y Acad Sci 845:1–10. https://doi.org/10.1111/j.1749-6632.1998.tb09657.x
Han C, Wen X, Zheng Q, Li H (2011) Effect of starvation on activities and mRNA expression of lipoprotein lipase and hormone-sensitive lipase in tilapia (Oreochromis niloticus × O. areus). Fish Physiol Biochem 37:113–122. https://doi.org/10.1007/s10695-010-9423-6
He A, Ning L, Chen L, Chen Y, Xing Q, Li J, Qiao F, Li D, Zhang M, Du Z (2015) Systemic adaptation of lipid metabolism in response to low- and high-fat diet in Nile tilapia (Oreochromis niloticus). Phys Rep 3:e12485. https://doi.org/10.14814/phy2.12485
Hildebrandt H, Jonas U, Ohashi M, Klaiber I, Rahman H (1999) Direct electrospray-ionization mass spectrometric analysis of the major ganglioside from crucian carp liver after thin layer chromatography. Comp Biochem Physiol B Biochem Mol Biol 122:83–88. https://doi.org/10.1016/S0305-0491(98)10152-9
Inamori K, Ito H, Tamura Y, Nitta T, Yang X, Nihei W, Shishido F, Imazu S, Tsukita S, Yamada T, Katagiri H, Inokuchi J (2018) Deficient ganglioside synthesis restores responsiveness to leptin and melanocortin signaling in obsess KKAy mice. J Lipid Res 59:1472–1481. https://doi.org/10.1194/jlr.M085753
Ince BW, Thorpe A (1976) The effects of starvation and force-feeding on the metabolism of the Northern pike, Esox LuciusL. J Fish Biol 8:79–88. https://doi.org/10.1111/j.1095-8649.1976.tb03909.x
Kaneko G, Yamada T, Han Y, Hirano Y, Khieokhajonkhet A, Shirakami H, Nagasaka R, Kondo H, Hirano I, Ushio H, Watabe S (2013) Differences in lipid distribution and expression of peroxisome proliferator-activated receptor gamma and lipoprotein lipase genes in torafugu and red seabream. Gen Comp Endocrinol 184:51–60. https://doi.org/10.1016/j.ygcen.2013.01.003
Kaneko G, Shirakami H, Hirano Y, Oba M, Yoshinaga H, Khieokhajonkhet A, Nagasaka R, Kondo H, Hirono I, Ushio H (2016a) Diversity of lipid distribution in fish skeletal muscle. Zool Sci 33:170–178. https://doi.org/10.2108/zs150096
Kaneko G, Shirakami H, Yamada T, Ide S, Haga Y, Satoh S, Ushio H (2016b) Short-term fasting increases skeletal muscle lipid content in association with enhanced mRNA levels of lipoprotein lipase 1 in lean juvenile red seabream (Pagrus major). Aquaculture 452:160–168. https://doi.org/10.1016/j.aquaculture.2015.10.030
Kang S, Jin U, Kim K, Lee Y, Park Y, Kim C (2007) Disialoganglioside GD3 increases in the secretion of apoB-containing lipoproteins. Biochem Biophys Res Commun 356:418–423. https://doi.org/10.1016/j.bbrc.2007.02.143
Khieokhajonkhet A, Kaneko G, Hirano Y, Wang L, Ushio H (2016) Different effects of growth hormone and fasting on the induction patterns of two hormone-sensitive lipase genes in red seabream Pagrus major. Gen Comp Endocrinol 236:121–130. https://doi.org/10.1016/j.ygcen.2016.06.025
Kittilson JD, Reindl KM, Sheridan MA (2011) Rainbow trout (Oncorhynchus mykiss) possess two hormone-sensitive lipase-encoding mRNAs that are differentially expressed and independently regulated by nutritional state. Comp Biochem Physiol A Mol Integr Physiol 158:52–60. https://doi.org/10.1016/j.cbpa.2010.09.010
Li H, Xu W, Jin J, Yang Y, Zhu X, Han D, Liu H, Xie S (2018) Effects of starvation on glucose and lipid metabolism in gibel carp (Carassius auratus gibel var. CAS III). Aquaculture 496:166–175. https://doi.org/10.1016/j.aquaculture.2018.07.015
Li K (1992) Determination of sialic acids in human serum by reversed-phase liquid chromatography with fluorimetric detection. J Chromatogr B Biomed Sci Appl 579:209–213. https://doi.org/10.1016/0378-4347(92)80384-3
Lipina C, Nardi F, Grace H, Hundal HS (2015) NEU3 sialidase as a marker of insulin sensitivity: Regulation by fatty acids. Cell Signal 27:1742–1750. https://doi.org/10.1016/j.cellsig.2015.05.010
Liu Y, Millar JS, Cromley DA, Graham M, Crooke R, Billheimer JT, Rader DJ (2008) Knockdown of Acyl-CoA:diacylglycerol acyltransferase 2 with antisense oligonucleotide reduces VLDL TG and ApoB secretion in mice. Biochim Biophys Acta 1781:97–104. https://doi.org/10.1016/j.bbalip.2008.01.001
Manzoni M, Colombi P, Papini N, Rubaga L, Tiso N, Preti A, Venerando B, Tettamanti G, Bresciani R, Argenton F, Borsani G, Monti E (2007) Molecular cloning and biochemical characterization of sialidases from zebrafish (Danio rerio). Biochem J 408:395–406. https://doi.org/10.1042/BJ20070627
McLaren DG, Han S, Murphy BA, Wilsie L, Stout SJ, Zhou H, Roddy TP, Gorski JN, Metzger DE, Shin MK, Reilly DF, Zhou HH, Tadin-Strapps M, Bartz SR, Cumiskey AM, Graham TH, Shen DM, Akinsanya KO, Previs SF, Imbriglio JE, Pinto S (2018) DGAT2 inhibition alters aspects of triglyceride metabolism in rodents but not in non-human primates. Cell Metab 27:1236–1248.e6. https://doi.org/10.1016/j.cmet.2018.04.004
Méndez G, Wieser W (1993) Metabolic responses to food deprivation and refeeding in juveniles of Rutilus rutilus (Teleostei: Cyprinidae). Environ Biol Fish 36:73–81. https://doi.org/10.1007/BF00005981
Nagafuku M, Sato T, Sato S, Shimizu K, Taira T, Inokuchi J (2015) Control of homeostatic and pathogenic balance in adipose tissue by ganglioside GM3. Glycobiology 25:303–318. https://doi.org/10.1093/glycob/cwu112
Nakamura H, Moriyama Y, Makiyama T, Emori S, Yamashita H, Yamazaki R, Murayama T (2013) Lactosylceramide interacts with and activates cytosolic phospholipase A2α. J Biol Chem 288:23264–23272. https://doi.org/10.1074/jbc.M113.491431
Ning L, He A, Li J, Lu D, Jiao J, Li L, Li D, Zhang M, Chen L, Du Z (2016) Mechanisms and metabolic regulation of PPARα activation in Nile tilapia (Oreochromis niloticus). Biochim Biophys Acta 1861:1036–1048. https://doi.org/10.1016/j.bbalip.2016.06.005
O’Connor PK, Reich B, Sheridan MA (1993) Growth hormone stimulates hepatic lipid mobilization in rainbow trout, Oncorhynchus mykiss. J Comp Physiol B 163:427–431. https://doi.org/10.1007/BF00265649
Ostrander GK, Bozlee M, Fukuda M, Dell A, Thomas-Oates JE, Levery SB, Eaton HL, Hakomori S, Holmes EH (1991) Isolation and characterization of the major glycosphingolipids from the liver of the rainbow trout (Oncorhynchus mykiss): Identification of an abundant source of 9-O-acetyl GD3. Arch Biochem Biophys 284:413–421. https://doi.org/10.1016/0003-9861(91)90317-C
Ostrander GK, Levery SB, Hakomori S, Holmes EH (1988) Isolation and characterization of the major acidic glycosphingolipids from the liver of the English sole (Parophrys ventulus). J Biol Chem 263:3103–3110
Saito M, Kitamura H, Sugiyama K (2001) Liver gangliosides of various animals ranging from fish to mammalian species. Comp Biochem Physiol B Biochem Mol Biol 129:747–758. https://doi.org/10.1016/S1096-4959(01)00379-7
Sheridan MA (1988) Lipid dynamics in fish: aspects of absorption, transportation, deposition and mobilization. Comp Biochem Physiol B 90:679–690. https://doi.org/10.1016/0305-0491(88)90322-7
Shiozaki K, Takeshita K, Ikeda M, Ikeda A, Harasaki Y, Komatsu M, Yamada S, Yamaguchi K, Miyagi T (2013) Molecular cloning and biochemical characterization of two novel Neu3 sialidases, neu3a and neu3b, from medaka (Oryzias latipes). Biochimie 95:280–289. https://doi.org/10.1016/j.biochi.2012.09.026
Shiozaki K, Ryuzono S, Matsushita N, Ikeda A, Takeshita K, Chigwechokha PK, Komatsu M, Miyagi T (2014) Molecular cloning and biochemical characterization of medaka (Oryzias latipes) lysosomal neu4 sialidase. Fish Physiol Biochem 40:1461–1472. https://doi.org/10.1007/s10695-014-9940-9
Tagami S, Inokuchi J, Kabayama K, Yoshimura H, Kitamura F, Uemura S, Ogawa C, Ishii A, Saito M, Ohtsuka Y, Sakaue S, Igrashi Y (2002) Ganglioside GM3 participates in the pathological conditions of insulin resistance. J Biol Chem 277:3085–3092. https://doi.org/10.1074/jbc.M103705200
Tian J, Wen H, Zeng L, Jiang M, Wu F, Liu W, Yang C (2013) Changes in the activities and mRNA expression levels of lipoprotein lipase (LPL), hormone-sensitive lipase (HSL) and fatty acid synthase (FAS) of Nile tilapia (Oreochromis niloticus) during fasting and re-feeding. Aquaculture 400–401:29–35. https://doi.org/10.1016/j.aquaculture.2013.01.032
Watanabe T, Sakiyama R, Iimi Y, Sekine S, Abe E, Nomura KH, Nomura K, Ishibashi Y, Okino N, Hayashi M, Ito M (2017) Regulation of TG accumulation and lipid droplet morphology by the novel TLDP1 in Aurantiochytrium limacinum F26-b. J Lipid Res 58:2334–2347. https://doi.org/10.1194/jlr.M079897
Weil C, Lefèvre F, Bugeon J (2013) Characteristics and metabolism of different adipose tissues in fish. Rev Fish Biol Fish 23:157–173. https://doi.org/10.1007/s11160-012-9288-0
Yamauchi Y, Furukawa K, Hamamura K, Furukawa K (2011) Positive feedback loop between PI3K-Akt-mTORC1 signaling and the lipogenic pathway boosts Akt signaling: Induction of the lipogenic pathway by a melanoma antigen. Cancer Res 71:4989–4997. https://doi.org/10.1158/0008-5472.CAN-10-4108
Yoshizumi S, Suzuki S, Hirai M, Hinokio Y, Yamada T, Yamada T, Tsunoda U, Aburatani H, Yamaguchi K, Miyagi T, Oka Y (2007) Increased hepatic expression of ganglioside-specific sialidase, NEU3, improves insulin sensitivity and glucose tolerance in mice. Metabolism 56:420–429. https://doi.org/10.1016/j.metabol.2006.10.027
Zeller CB, Marchase RB (1992) Gangliosides as modulators of cell function. Am J Phys 262:C1341–C1355. https://doi.org/10.1152/ajpcell.1992.262.6.C1341
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.
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10695-019-00730-6