Zebrafish Models for Dyslipidemia and Atherosclerosis Research

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2016 Dec 27

PMID 28018294

Citations 21

Authors

Amnon Schlegel

Affiliations

Soon will be listed here.

Abstract

Atherosclerotic cardiovascular disease is the leading cause of death. Elevated circulating concentrations of lipids are a central pathogenetic driver of atherosclerosis. While numerous effective therapies for this condition have been developed, there is substantial unmet need for this pandemic illness. Here, I will review nutritional, physiological, genetic, and pathological discoveries in the emerging zebrafish model for studying dyslipidemia and atherosclerosis. The technical and physiological advantages and the pharmacological potential of this organism for discovery and validation of dyslipidemia and atherosclerosis targets are stressed through summary of recent findings. An emerging literature shows that zebrafish, through retention of a ortholog gene and high sensitivity to ingestion of excess cholesterol, rapidly develops hypercholesterolemia, with a pattern of distribution of lipid species in lipoprotein particles similar to humans. Furthermore, recent studies leveraging the optical transparency of zebrafish larvae to monitor the fate of these ingested lipids have provided exciting insights to the development of dyslipidemia and atherosclerosis. Future directions for investigation are considered, with particular attention to the potential for cell biological study of atherosclerotic plaques.

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References

Nicholls S, Brewer H, Kastelein J, Krueger K, Wang M, Shao M . Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on HDL and LDL cholesterol: a randomized controlled trial. JAMA. 2011; 306(19):2099-109. DOI: 10.1001/jama.2011.1649. View

Kirchgessner T, Sleph P, Ostrowski J, Lupisella J, Ryan C, Liu X . Beneficial and Adverse Effects of an LXR Agonist on Human Lipid and Lipoprotein Metabolism and Circulating Neutrophils. Cell Metab. 2016; 24(2):223-33. DOI: 10.1016/j.cmet.2016.07.016. View

Calkin A, Tontonoz P . Transcriptional integration of metabolism by the nuclear sterol-activated receptors LXR and FXR. Nat Rev Mol Cell Biol. 2012; 13(4):213-24. PMC: 3597092. DOI: 10.1038/nrm3312. View

Willer C, Schmidt E, Sengupta S, Peloso G, Gustafsson S, Kanoni S . Discovery and refinement of loci associated with lipid levels. Nat Genet. 2013; 45(11):1274-1283. PMC: 3838666. DOI: 10.1038/ng.2797. View

Jin S, Cho K . Water extracts of cinnamon and clove exhibits potent inhibition of protein glycation and anti-atherosclerotic activity in vitro and in vivo hypolipidemic activity in zebrafish. Food Chem Toxicol. 2011; 49(7):1521-9. DOI: 10.1016/j.fct.2011.03.043. View

Hoshijima K, Jurynec M, Grunwald D . Precise Editing of the Zebrafish Genome Made Simple and Efficient. Dev Cell. 2016; 36(6):654-67. PMC: 4806538. DOI: 10.1016/j.devcel.2016.02.015. View

Hall J, Qiu X . Structural and biophysical insight into cholesteryl ester-transfer protein. Biochem Soc Trans. 2011; 39(4):1000-5. DOI: 10.1042/BST0391000. View

Kimura Y, Hisano Y, Kawahara A, Higashijima S . Efficient generation of knock-in transgenic zebrafish carrying reporter/driver genes by CRISPR/Cas9-mediated genome engineering. Sci Rep. 2014; 4:6545. PMC: 4189020. DOI: 10.1038/srep06545. View

Kim J, Seo J, Cho K . Aspartame-fed zebrafish exhibit acute deaths with swimming defects and saccharin-fed zebrafish have elevation of cholesteryl ester transfer protein activity in hypercholesterolemia. Food Chem Toxicol. 2011; 49(11):2899-905. DOI: 10.1016/j.fct.2011.08.001. View

10.

Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss C, Maza O . Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014; 514(7521):181-6. DOI: 10.1038/nature13793. View

11.

Fang L, Harkewicz R, Hartvigsen K, Wiesner P, Choi S, Almazan F . Oxidized cholesteryl esters and phospholipids in zebrafish larvae fed a high cholesterol diet: macrophage binding and activation. J Biol Chem. 2010; 285(42):32343-51. PMC: 2952235. DOI: 10.1074/jbc.M110.137257. View

12.

Jin S, Hong J, Jung S, Cho K . Turmeric and laurel aqueous extracts exhibit in vitro anti-atherosclerotic activity and in vivo hypolipidemic effects in a zebrafish model. J Med Food. 2011; 14(3):247-56. DOI: 10.1089/jmf.2009.1389. View

13.

Baggio G, Manzato E, Gabelli C, Fellin R, Martini S, Enzi G . Apolipoprotein C-II deficiency syndrome. Clinical features, lipoprotein characterization, lipase activity, and correction of hypertriglyceridemia after apolipoprotein C-II administration in two affected patients. J Clin Invest. 1986; 77(2):520-7. PMC: 423374. DOI: 10.1172/JCI112332. View

14.

Gut P, Baeza-Raja B, Andersson O, Hasenkamp L, Hsiao J, Hesselson D . Whole-organism screening for gluconeogenesis identifies activators of fasting metabolism. Nat Chem Biol. 2012; 9(2):97-104. PMC: 3552031. DOI: 10.1038/nchembio.1136. View

15.

Uhlen M, Fagerberg L, Hallstrom B, Lindskog C, Oksvold P, Mardinoglu A . Proteomics. Tissue-based map of the human proteome. Science. 2015; 347(6220):1260419. DOI: 10.1126/science.1260419. View

16.

Babin P, Gibbons G . The evolution of plasma cholesterol: direct utility or a "spandrel" of hepatic lipid metabolism?. Prog Lipid Res. 2008; 48(2):73-91. DOI: 10.1016/j.plipres.2008.11.002. View

17.

Danaei G, Finucane M, Lin J, Singh G, Paciorek C, Cowan M . National, regional, and global trends in systolic blood pressure since 1980: systematic analysis of health examination surveys and epidemiological studies with 786 country-years and 5·4 million participants. Lancet. 2011; 377(9765):568-77. DOI: 10.1016/S0140-6736(10)62036-3. View

18.

Young S, Zechner R . Biochemistry and pathophysiology of intravascular and intracellular lipolysis. Genes Dev. 2013; 27(5):459-84. PMC: 3605461. DOI: 10.1101/gad.209296.112. View

19.

Danaei G, Finucane M, Lu Y, Singh G, Cowan M, Paciorek C . National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants. Lancet. 2011; 378(9785):31-40. DOI: 10.1016/S0140-6736(11)60679-X. View

20.

Zhang S, Reddick R, Piedrahita J, Maeda N . Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science. 1992; 258(5081):468-71. DOI: 10.1126/science.1411543. View