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Nutrients 2017, 9(9), 1018; doi:10.3390/nu9091018

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

1
College of Life and Health Sciences, Chubu University, 487-8501 Kasugai, Japan
2
Department of Public Health, Fujita Health University School of Medicine, 470-1192 Toyoake, Japan
3
National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, 100050 Beijing, China
4
College of Human Life and Environment, Kinjo Gakuin University, 463-8521 Nagoya, Japan
*
Author to whom correspondence should be addressed.
Received: 13 July 2017 / Revised: 29 August 2017 / Accepted: 11 September 2017 / Published: 14 September 2017
(This article belongs to the Special Issue Nutrition and Non-alcoholic Fatty Liver Disease)
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Abstract

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. View Full-Text
Keywords: 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 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
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Yuan, Y.; Naito, H.; Jia, X.; Kitamori, K.; Nakajima, T. 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 2017, 9, 1018.

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