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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ftdoajarticles:oai:doaj.org/article:3b3919fd216a41cab30b526aaa76c70c 2023-05-15T16:55:19+02:00 Exposure to a northern contaminant mixture (NCM) alters hepatic energy and lipid metabolism exacerbating hepatic steatosis in obese JCR rats. 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 2014-01-01T00:00:00Z https://doi.org/10.1371/journal.pone.0106832 https://doaj.org/article/3b3919fd216a41cab30b526aaa76c70c EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pone.0106832 https://doaj.org/toc/1932-6203 1932-6203 doi:10.1371/journal.pone.0106832 https://doaj.org/article/3b3919fd216a41cab30b526aaa76c70c PLoS ONE, Vol 9, Iss 9, p e106832 (2014) Medicine R Science Q article 2014 ftdoajarticles https://doi.org/10.1371/journal.pone.0106832 2022-12-31T13:42:50Z 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. Article in Journal/Newspaper inuit Directory of Open Access Journals: DOAJ Articles Canada PLoS ONE 9 9 e106832 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
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. |
topic_facet |
Medicine R Science Q |
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 in Journal/Newspaper |
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://doi.org/10.1371/journal.pone.0106832 https://doaj.org/article/3b3919fd216a41cab30b526aaa76c70c |
geographic |
Canada |
geographic_facet |
Canada |
genre |
inuit |
genre_facet |
inuit |
op_source |
PLoS ONE, Vol 9, Iss 9, p e106832 (2014) |
op_relation |
https://doi.org/10.1371/journal.pone.0106832 https://doaj.org/toc/1932-6203 1932-6203 doi:10.1371/journal.pone.0106832 https://doaj.org/article/3b3919fd216a41cab30b526aaa76c70c |
op_doi |
https://doi.org/10.1371/journal.pone.0106832 |
container_title |
PLoS ONE |
container_volume |
9 |
container_issue |
9 |
container_start_page |
e106832 |
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