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Modified Lipoproteins by Acrylamide Showed More Atherogenic Properties and Exposure of Acrylamide Induces Acute Hyperlipidemia and Fatty Liver Changes in Zebrafish

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Abstract

Acrylamide is a well-known potent carcinogen and neurotoxin that, until now, has not been sufficiently investigated with regard to its effects on lipid metabolism. We investigated physiological effects of acrylamide (AA) on lipoprotein metabolism using human macrophages, dermal cells, and zebrafish models. Functional and structural properties of lipoproteins were modified by AA (final concentration of 5–100 mM) with loss of antioxidant ability and multimerization of apoA-I in vitro. AA exacerbated LDL oxidation, degradation, and LDL uptake into macrophages with increased ROS production. In human cells, treatment of AA (1–100 μM) caused cellular senescence of dermal cells with severe cytotoxicity. Waterborne exposure of zebrafish in cage water containing AA (300 ppm) resulted in acute death within 26 h along with elevation of body weight, blood glucose, triglyceride, and hepatic inflammation. AA exposure caused fat accumulation in liver in a dose-dependent manner. In conclusion, AA affected lipoprotein metabolism to result exacerbation of atherosclerosis. Exposure of zebrafish to AA resulted in acute inflammatory death with hyperlipidemia.

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Abbreviations

AA:

Acrylamide

GOT:

Glutamic oxaloacetic transaminase

GPT:

Glutamic pyruvic transaminase

HCD:

High-cholesterol diet

HDL:

High-density lipoproteins

LDL:

Low-density lipoproteins

ND:

Normal diet

TC:

Total cholesterol

TG:

Triglycerides

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Acknowledgments

This work was supported by the Mid-carrier Researcher Program (2014-11049455) and Basic Science Research (2010-020910) program through the National Research Foundation of Korea (NRF). The authors are grateful for the BK21 plus program of the National Research Foundation for the support of graduate students.

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No competing financial interests exist.

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Correspondence to Kyung-Hyun Cho.

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Seong-Min Kim, Ji-Mi Baek and So-Mang Lim are co-first authors.

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Kim, SM., Baek, JM., Lim, SM. et al. Modified Lipoproteins by Acrylamide Showed More Atherogenic Properties and Exposure of Acrylamide Induces Acute Hyperlipidemia and Fatty Liver Changes in Zebrafish. Cardiovasc Toxicol 15, 300–308 (2015). https://doi.org/10.1007/s12012-014-9294-7

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