Hepatic overproduction of 13-HODE due to ALOX15 upregulation contributes to alcohol-induced liver injury in mice

Abstract Chronic alcohol feeding causes lipid accumulation and apoptosis in the liver. This study investigated the role of bioactive lipid metabolites in alcohol-induced liver damage and tested the potential of targeting arachidonate 15-lipoxygenase (ALOX15) in treating alcoholic liver disease (ALD)...

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Autores principales:	Wenliang Zhang, Wei Zhong, Qian Sun, Xinguo Sun, Zhanxiang Zhou
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1aba9f6d9cdf4cc3bf943832ff1fce73
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spelling	oai:doaj.org-article:1aba9f6d9cdf4cc3bf943832ff1fce732021-12-02T15:05:08ZHepatic overproduction of 13-HODE due to ALOX15 upregulation contributes to alcohol-induced liver injury in mice10.1038/s41598-017-02759-02045-2322https://doaj.org/article/1aba9f6d9cdf4cc3bf943832ff1fce732017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02759-0https://doaj.org/toc/2045-2322Abstract Chronic alcohol feeding causes lipid accumulation and apoptosis in the liver. This study investigated the role of bioactive lipid metabolites in alcohol-induced liver damage and tested the potential of targeting arachidonate 15-lipoxygenase (ALOX15) in treating alcoholic liver disease (ALD). Results showed that chronic alcohol exposure induced hepatocyte apoptosis in association with increased hepatic 13-HODE. Exposure of 13-HODE to Hepa-1c1c7 cells induced oxidative stress, ER stress and apoptosis. 13-HODE also perturbed proteins related to lipid metabolism. HODE-generating ALOX15 was up-regulated by chronic alcohol exposure. Linoleic acid, but not ethanol or acetaldehyde, induced ALOX15 expression in Hepa-1c1c7 cells. ALOX15 knockout prevented alcohol-induced liver damage via attenuation of oxidative stress, ER stress, lipid metabolic disorder, and cell death signaling. ALOX15 inhibitor (PD146176) treatment also significantly alleviated alcohol-induced oxidative stress, lipid accumulation and liver damage. These results demonstrated that activation of ALOX15/13-HODE circuit critically mediates the pathogenesis of ALD. This study suggests that ALOX15 is a potential molecular target for treatment of ALD.Wenliang ZhangWei ZhongQian SunXinguo SunZhanxiang ZhouNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wenliang Zhang Wei Zhong Qian Sun Xinguo Sun Zhanxiang Zhou Hepatic overproduction of 13-HODE due to ALOX15 upregulation contributes to alcohol-induced liver injury in mice
description	Abstract Chronic alcohol feeding causes lipid accumulation and apoptosis in the liver. This study investigated the role of bioactive lipid metabolites in alcohol-induced liver damage and tested the potential of targeting arachidonate 15-lipoxygenase (ALOX15) in treating alcoholic liver disease (ALD). Results showed that chronic alcohol exposure induced hepatocyte apoptosis in association with increased hepatic 13-HODE. Exposure of 13-HODE to Hepa-1c1c7 cells induced oxidative stress, ER stress and apoptosis. 13-HODE also perturbed proteins related to lipid metabolism. HODE-generating ALOX15 was up-regulated by chronic alcohol exposure. Linoleic acid, but not ethanol or acetaldehyde, induced ALOX15 expression in Hepa-1c1c7 cells. ALOX15 knockout prevented alcohol-induced liver damage via attenuation of oxidative stress, ER stress, lipid metabolic disorder, and cell death signaling. ALOX15 inhibitor (PD146176) treatment also significantly alleviated alcohol-induced oxidative stress, lipid accumulation and liver damage. These results demonstrated that activation of ALOX15/13-HODE circuit critically mediates the pathogenesis of ALD. This study suggests that ALOX15 is a potential molecular target for treatment of ALD.
format	article
author	Wenliang Zhang Wei Zhong Qian Sun Xinguo Sun Zhanxiang Zhou
author_facet	Wenliang Zhang Wei Zhong Qian Sun Xinguo Sun Zhanxiang Zhou
author_sort	Wenliang Zhang
title	Hepatic overproduction of 13-HODE due to ALOX15 upregulation contributes to alcohol-induced liver injury in mice
title_short	Hepatic overproduction of 13-HODE due to ALOX15 upregulation contributes to alcohol-induced liver injury in mice
title_full	Hepatic overproduction of 13-HODE due to ALOX15 upregulation contributes to alcohol-induced liver injury in mice
title_fullStr	Hepatic overproduction of 13-HODE due to ALOX15 upregulation contributes to alcohol-induced liver injury in mice
title_full_unstemmed	Hepatic overproduction of 13-HODE due to ALOX15 upregulation contributes to alcohol-induced liver injury in mice
title_sort	hepatic overproduction of 13-hode due to alox15 upregulation contributes to alcohol-induced liver injury in mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/1aba9f6d9cdf4cc3bf943832ff1fce73
work_keys_str_mv	AT wenliangzhang hepaticoverproductionof13hodeduetoalox15upregulationcontributestoalcoholinducedliverinjuryinmice AT weizhong hepaticoverproductionof13hodeduetoalox15upregulationcontributestoalcoholinducedliverinjuryinmice AT qiansun hepaticoverproductionof13hodeduetoalox15upregulationcontributestoalcoholinducedliverinjuryinmice AT xinguosun hepaticoverproductionof13hodeduetoalox15upregulationcontributestoalcoholinducedliverinjuryinmice AT zhanxiangzhou hepaticoverproductionof13hodeduetoalox15upregulationcontributestoalcoholinducedliverinjuryinmice
_version_	1718388877150912512

Hepatic overproduction of 13-HODE due to ALOX15 upregulation contributes to alcohol-induced liver injury in mice

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