Exposure to a northern contaminant mixture (NCM) alters hepatic energy and lipid metabolism exacerbating hepatic steatosis in obese JCR rats.

Non-alcoholic fatty liver disease (NAFLD), defined by the American Liver Society as the buildup of extra fat in liver cells that is not caused by alcohol, is the most common liver disease in North America. Obesity and type 2 diabetes are viewed as the major causes of NAFLD. Environmental contaminant...

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Autores principales:	Ryan J Mailloux, Maria Florian, Qixuan Chen, Jin Yan, Ivan Petrov, Melanie C Coughlan, Mahemuti Laziyan, Don Caldwell, Michelle Lalande, Dominique Patry, Claude Gagnon, Kurtis Sarafin, Jocelyn Truong, Hing Man Chan, Nimal Ratnayake, Nanqin Li, William G Willmore, Xiaolei Jin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3b3919fd216a41cab30b526aaa76c70c
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spelling	oai:doaj.org-article:3b3919fd216a41cab30b526aaa76c70c2021-11-25T06:00:40ZExposure to a northern contaminant mixture (NCM) alters hepatic energy and lipid metabolism exacerbating hepatic steatosis in obese JCR rats.1932-620310.1371/journal.pone.0106832https://doaj.org/article/3b3919fd216a41cab30b526aaa76c70c2014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0106832https://doaj.org/toc/1932-6203Non-alcoholic fatty liver disease (NAFLD), defined by the American Liver Society as the buildup of extra fat in liver cells that is not caused by alcohol, is the most common liver disease in North America. Obesity and type 2 diabetes are viewed as the major causes of NAFLD. Environmental contaminants have also been implicated in the development of NAFLD. Northern populations are exposed to a myriad of persistent organic pollutants including polychlorinated biphenyls, organochlorine pesticides, flame retardants, and toxic metals, while also affected by higher rates of obesity and alcohol abuse compared to the rest of Canada. In this study, we examined the impact of a mixture of 22 contaminants detected in Inuit blood on the development and progression of NAFLD in obese JCR rats with or without co-exposure to 10% ethanol. Hepatosteatosis was found in obese rat liver, which was worsened by exposure to 10% ethanol. NCM treatment increased the number of macrovesicular lipid droplets, total lipid contents, portion of mono- and polyunsaturated fatty acids in the liver. This was complemented by an increase in hepatic total cholesterol and cholesterol ester levels which was associated with changes in the expression of genes and proteins involved in lipid metabolism and transport. In addition, NCM treatment increased cytochrome P450 2E1 protein expression and decreased ubiquinone pool, and mitochondrial ATP synthase subunit ATP5A and Complex IV activity. Despite the changes in mitochondrial physiology, hepatic ATP levels were maintained high in NCM-treated versus control rats. This was due to a decrease in ATP utilization and an increase in creatine kinase activity. Collectively, our results suggest that NCM treatment decreases hepatic cholesterol export, possibly also increases cholesterol uptake from circulation, and promotes lipid accumulation and alters ATP homeostasis which exacerbates the existing hepatic steatosis in genetically obese JCR rats with or without co-exposure to ethanol.Ryan J MaillouxMaria FlorianQixuan ChenJin YanIvan PetrovMelanie C CoughlanMahemuti LaziyanDon CaldwellMichelle LalandeDominique PatryClaude GagnonKurtis SarafinJocelyn TruongHing Man ChanNimal RatnayakeNanqin LiWilliam G WillmoreXiaolei JinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e106832 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ryan J Mailloux Maria Florian Qixuan Chen Jin Yan Ivan Petrov Melanie C Coughlan Mahemuti Laziyan Don Caldwell Michelle Lalande Dominique Patry Claude Gagnon Kurtis Sarafin Jocelyn Truong Hing Man Chan Nimal Ratnayake Nanqin Li William G Willmore Xiaolei Jin Exposure to a northern contaminant mixture (NCM) alters hepatic energy and lipid metabolism exacerbating hepatic steatosis in obese JCR rats.
description	Non-alcoholic fatty liver disease (NAFLD), defined by the American Liver Society as the buildup of extra fat in liver cells that is not caused by alcohol, is the most common liver disease in North America. Obesity and type 2 diabetes are viewed as the major causes of NAFLD. Environmental contaminants have also been implicated in the development of NAFLD. Northern populations are exposed to a myriad of persistent organic pollutants including polychlorinated biphenyls, organochlorine pesticides, flame retardants, and toxic metals, while also affected by higher rates of obesity and alcohol abuse compared to the rest of Canada. In this study, we examined the impact of a mixture of 22 contaminants detected in Inuit blood on the development and progression of NAFLD in obese JCR rats with or without co-exposure to 10% ethanol. Hepatosteatosis was found in obese rat liver, which was worsened by exposure to 10% ethanol. NCM treatment increased the number of macrovesicular lipid droplets, total lipid contents, portion of mono- and polyunsaturated fatty acids in the liver. This was complemented by an increase in hepatic total cholesterol and cholesterol ester levels which was associated with changes in the expression of genes and proteins involved in lipid metabolism and transport. In addition, NCM treatment increased cytochrome P450 2E1 protein expression and decreased ubiquinone pool, and mitochondrial ATP synthase subunit ATP5A and Complex IV activity. Despite the changes in mitochondrial physiology, hepatic ATP levels were maintained high in NCM-treated versus control rats. This was due to a decrease in ATP utilization and an increase in creatine kinase activity. Collectively, our results suggest that NCM treatment decreases hepatic cholesterol export, possibly also increases cholesterol uptake from circulation, and promotes lipid accumulation and alters ATP homeostasis which exacerbates the existing hepatic steatosis in genetically obese JCR rats with or without co-exposure to ethanol.
format	article
author	Ryan J Mailloux Maria Florian Qixuan Chen Jin Yan Ivan Petrov Melanie C Coughlan Mahemuti Laziyan Don Caldwell Michelle Lalande Dominique Patry Claude Gagnon Kurtis Sarafin Jocelyn Truong Hing Man Chan Nimal Ratnayake Nanqin Li William G Willmore Xiaolei Jin
author_facet	Ryan J Mailloux Maria Florian Qixuan Chen Jin Yan Ivan Petrov Melanie C Coughlan Mahemuti Laziyan Don Caldwell Michelle Lalande Dominique Patry Claude Gagnon Kurtis Sarafin Jocelyn Truong Hing Man Chan Nimal Ratnayake Nanqin Li William G Willmore Xiaolei Jin
author_sort	Ryan J Mailloux
title	Exposure to a northern contaminant mixture (NCM) alters hepatic energy and lipid metabolism exacerbating hepatic steatosis in obese JCR rats.
title_short	Exposure to a northern contaminant mixture (NCM) alters hepatic energy and lipid metabolism exacerbating hepatic steatosis in obese JCR rats.
title_full	Exposure to a northern contaminant mixture (NCM) alters hepatic energy and lipid metabolism exacerbating hepatic steatosis in obese JCR rats.
title_fullStr	Exposure to a northern contaminant mixture (NCM) alters hepatic energy and lipid metabolism exacerbating hepatic steatosis in obese JCR rats.
title_full_unstemmed	Exposure to a northern contaminant mixture (NCM) alters hepatic energy and lipid metabolism exacerbating hepatic steatosis in obese JCR rats.
title_sort	exposure to a northern contaminant mixture (ncm) alters hepatic energy and lipid metabolism exacerbating hepatic steatosis in obese jcr rats.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/3b3919fd216a41cab30b526aaa76c70c
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Exposure to a northern contaminant mixture (NCM) alters hepatic energy and lipid metabolism exacerbating hepatic steatosis in obese JCR rats.

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