Combination of Hypertension Along with a High Fat and Cholesterol Diet Induces Severe Hepatic Inflammation in Rats via a Signaling Network Comprising NF-κB, MAPK, and Nrf2 Pathways
Populations with essential hypertension have a high risk of nonalcoholic steatohepatitis (NASH). In this study, we investigated the mechanism that underlies the progression of hypertension-associated NASH by comparing differences in the development of high fat and cholesterol (HFC) diet-induced NASH...
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doaj-e3de5e6dd218489aa9ea1ff61f9da0382020-11-25T01:05:47ZengMDPI AGNutrients2072-66432017-09-0199101810.3390/nu9091018nu9091018Combination of Hypertension Along with a High Fat and Cholesterol Diet Induces Severe Hepatic Inflammation in Rats via a Signaling Network Comprising NF-κB, MAPK, and Nrf2 PathwaysYuan Yuan0Hisao Naito1Xiaofang Jia2Kazuya Kitamori3Tamie Nakajima4College of Life and Health Sciences, Chubu University, 487-8501 Kasugai, JapanDepartment of Public Health, Fujita Health University School of Medicine, 470-1192 Toyoake, JapanNational Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, 100050 Beijing, ChinaCollege of Human Life and Environment, Kinjo Gakuin University, 463-8521 Nagoya, JapanCollege of Life and Health Sciences, Chubu University, 487-8501 Kasugai, JapanPopulations with essential hypertension have a high risk of nonalcoholic steatohepatitis (NASH). In this study, we investigated the mechanism that underlies the progression of hypertension-associated NASH by comparing differences in the development of high fat and cholesterol (HFC) diet-induced NASH among three strains of rats, i.e., two hypertensive strains comprising spontaneously hypertensive rats and the stroke-prone spontaneously hypertensive 5/Dmcr, and the original Wistar Kyoto rats as the normotensive control. We investigated histopathological changes and molecular signals related to inflammation in the liver after feeding with the HFC diet for 8 weeks. The diet induced severe lobular inflammation and fibrosis in the livers of the hypertensive rats, whereas it only caused mild steatohepatitis in the normotensive rats. An increased activation of proinflammatory signaling (transforming growth factor-β1/mitogen-activated protein kinases pathway) was observed in the hypertensive strains fed with the HFC diet. In addition, the HFC diet suppressed the nuclear factor erythroid 2-related factor 2 pathway in the hypertensive rats and led to lower increases in the hepatic expression of heme oxygenase-1, which has anti-oxidative and anti-inflammatory activities. In conclusion, these signaling pathways might play crucial roles in the development of hypertension-associated NASH.https://www.mdpi.com/2072-6643/9/9/1018hepatic inflammationhigh-fat-cholesterol diethypertensionmitogen-activated protein kinasenonalcoholic steatohepatitisnuclear factor erythroid 2-related factor 2 pathwaynuclear factor-kappa Bspontaneously hypertensive ratstroke-prone spontaneously hypertensive5/DmcrWistar Kyoto |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yuan Yuan Hisao Naito Xiaofang Jia Kazuya Kitamori Tamie Nakajima |
spellingShingle |
Yuan Yuan Hisao Naito Xiaofang Jia Kazuya Kitamori Tamie Nakajima Combination of Hypertension Along with a High Fat and Cholesterol Diet Induces Severe Hepatic Inflammation in Rats via a Signaling Network Comprising NF-κB, MAPK, and Nrf2 Pathways Nutrients hepatic inflammation high-fat-cholesterol diet hypertension mitogen-activated protein kinase nonalcoholic steatohepatitis nuclear factor erythroid 2-related factor 2 pathway nuclear factor-kappa B spontaneously hypertensive rat stroke-prone spontaneously hypertensive5/Dmcr Wistar Kyoto |
author_facet |
Yuan Yuan Hisao Naito Xiaofang Jia Kazuya Kitamori Tamie Nakajima |
author_sort |
Yuan Yuan |
title |
Combination of Hypertension Along with a High Fat and Cholesterol Diet Induces Severe Hepatic Inflammation in Rats via a Signaling Network Comprising NF-κB, MAPK, and Nrf2 Pathways |
title_short |
Combination of Hypertension Along with a High Fat and Cholesterol Diet Induces Severe Hepatic Inflammation in Rats via a Signaling Network Comprising NF-κB, MAPK, and Nrf2 Pathways |
title_full |
Combination of Hypertension Along with a High Fat and Cholesterol Diet Induces Severe Hepatic Inflammation in Rats via a Signaling Network Comprising NF-κB, MAPK, and Nrf2 Pathways |
title_fullStr |
Combination of Hypertension Along with a High Fat and Cholesterol Diet Induces Severe Hepatic Inflammation in Rats via a Signaling Network Comprising NF-κB, MAPK, and Nrf2 Pathways |
title_full_unstemmed |
Combination of Hypertension Along with a High Fat and Cholesterol Diet Induces Severe Hepatic Inflammation in Rats via a Signaling Network Comprising NF-κB, MAPK, and Nrf2 Pathways |
title_sort |
combination of hypertension along with a high fat and cholesterol diet induces severe hepatic inflammation in rats via a signaling network comprising nf-κb, mapk, and nrf2 pathways |
publisher |
MDPI AG |
series |
Nutrients |
issn |
2072-6643 |
publishDate |
2017-09-01 |
description |
Populations with essential hypertension have a high risk of nonalcoholic steatohepatitis (NASH). In this study, we investigated the mechanism that underlies the progression of hypertension-associated NASH by comparing differences in the development of high fat and cholesterol (HFC) diet-induced NASH among three strains of rats, i.e., two hypertensive strains comprising spontaneously hypertensive rats and the stroke-prone spontaneously hypertensive 5/Dmcr, and the original Wistar Kyoto rats as the normotensive control. We investigated histopathological changes and molecular signals related to inflammation in the liver after feeding with the HFC diet for 8 weeks. The diet induced severe lobular inflammation and fibrosis in the livers of the hypertensive rats, whereas it only caused mild steatohepatitis in the normotensive rats. An increased activation of proinflammatory signaling (transforming growth factor-β1/mitogen-activated protein kinases pathway) was observed in the hypertensive strains fed with the HFC diet. In addition, the HFC diet suppressed the nuclear factor erythroid 2-related factor 2 pathway in the hypertensive rats and led to lower increases in the hepatic expression of heme oxygenase-1, which has anti-oxidative and anti-inflammatory activities. In conclusion, these signaling pathways might play crucial roles in the development of hypertension-associated NASH. |
topic |
hepatic inflammation high-fat-cholesterol diet hypertension mitogen-activated protein kinase nonalcoholic steatohepatitis nuclear factor erythroid 2-related factor 2 pathway nuclear factor-kappa B spontaneously hypertensive rat stroke-prone spontaneously hypertensive5/Dmcr Wistar Kyoto |
url |
https://www.mdpi.com/2072-6643/9/9/1018 |
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