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Dietary Iron Supplementation Alters Hepatic Inflammation in a Rat Model of Nonalcoholic Steatohepatitis

Nonalcoholic fatty liver disease (NAFLD) is now the most common liver disease in the world. NAFLD can progress to nonalcoholic steatohepatitis (NASH), cirrhosis and eventually hepatocellular carcinoma. Acquired hepatic iron overload is seen in a number of patients with NAFLD; however, its significan...

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Autores principales: Atarashi, Machi, Izawa, Takeshi, Miyagi, Rena, Ohji, Shoko, Hashimoto, Ai, Kuwamura, Mitsuru, Yamate, Jyoji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852751/
https://www.ncbi.nlm.nih.gov/pubmed/29401710
http://dx.doi.org/10.3390/nu10020175
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author Atarashi, Machi
Izawa, Takeshi
Miyagi, Rena
Ohji, Shoko
Hashimoto, Ai
Kuwamura, Mitsuru
Yamate, Jyoji
author_facet Atarashi, Machi
Izawa, Takeshi
Miyagi, Rena
Ohji, Shoko
Hashimoto, Ai
Kuwamura, Mitsuru
Yamate, Jyoji
author_sort Atarashi, Machi
collection PubMed
description Nonalcoholic fatty liver disease (NAFLD) is now the most common liver disease in the world. NAFLD can progress to nonalcoholic steatohepatitis (NASH), cirrhosis and eventually hepatocellular carcinoma. Acquired hepatic iron overload is seen in a number of patients with NAFLD; however, its significance in the pathology of NAFLD is still debated. Here, we investigated the role of dietary iron supplementation in experimental steatohepatitis in rats. Rats were fed a control, high-fat (HF), high-fat high-iron (HFHI) and high-iron (HI) diet for 30 weeks. Blood biochemical, histopathological and gut microbiota analyses were performed. Rats in HF and HFHI groups showed an ALT-dominant elevation of serum transaminases, hepatic steatosis, hepatic inflammation, and upregulation of proinflammatory cytokines. The number of large inflammatory foci, corresponding to lobular inflammation in NASH patients, was significantly higher in HFHI than in HF group; within the lesion, macrophages with intense iron staining were observed. Hepatic expression of TNFα was higher in HFHI than that in HF group. There was no significant change in hepatic oxidative stress, gut microbiota or serum endotoxin levels between HF and HFHI groups. These results suggested that dietary iron supplementation enhances experimental steatohepatitis induced by long-term high-fat diet feeding in rats. Iron-laden macrophages can play an important role in the enhancement of hepatic inflammation.
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spelling pubmed-58527512018-03-19 Dietary Iron Supplementation Alters Hepatic Inflammation in a Rat Model of Nonalcoholic Steatohepatitis Atarashi, Machi Izawa, Takeshi Miyagi, Rena Ohji, Shoko Hashimoto, Ai Kuwamura, Mitsuru Yamate, Jyoji Nutrients Article Nonalcoholic fatty liver disease (NAFLD) is now the most common liver disease in the world. NAFLD can progress to nonalcoholic steatohepatitis (NASH), cirrhosis and eventually hepatocellular carcinoma. Acquired hepatic iron overload is seen in a number of patients with NAFLD; however, its significance in the pathology of NAFLD is still debated. Here, we investigated the role of dietary iron supplementation in experimental steatohepatitis in rats. Rats were fed a control, high-fat (HF), high-fat high-iron (HFHI) and high-iron (HI) diet for 30 weeks. Blood biochemical, histopathological and gut microbiota analyses were performed. Rats in HF and HFHI groups showed an ALT-dominant elevation of serum transaminases, hepatic steatosis, hepatic inflammation, and upregulation of proinflammatory cytokines. The number of large inflammatory foci, corresponding to lobular inflammation in NASH patients, was significantly higher in HFHI than in HF group; within the lesion, macrophages with intense iron staining were observed. Hepatic expression of TNFα was higher in HFHI than that in HF group. There was no significant change in hepatic oxidative stress, gut microbiota or serum endotoxin levels between HF and HFHI groups. These results suggested that dietary iron supplementation enhances experimental steatohepatitis induced by long-term high-fat diet feeding in rats. Iron-laden macrophages can play an important role in the enhancement of hepatic inflammation. MDPI 2018-02-04 /pmc/articles/PMC5852751/ /pubmed/29401710 http://dx.doi.org/10.3390/nu10020175 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Atarashi, Machi
Izawa, Takeshi
Miyagi, Rena
Ohji, Shoko
Hashimoto, Ai
Kuwamura, Mitsuru
Yamate, Jyoji
Dietary Iron Supplementation Alters Hepatic Inflammation in a Rat Model of Nonalcoholic Steatohepatitis
title Dietary Iron Supplementation Alters Hepatic Inflammation in a Rat Model of Nonalcoholic Steatohepatitis
title_full Dietary Iron Supplementation Alters Hepatic Inflammation in a Rat Model of Nonalcoholic Steatohepatitis
title_fullStr Dietary Iron Supplementation Alters Hepatic Inflammation in a Rat Model of Nonalcoholic Steatohepatitis
title_full_unstemmed Dietary Iron Supplementation Alters Hepatic Inflammation in a Rat Model of Nonalcoholic Steatohepatitis
title_short Dietary Iron Supplementation Alters Hepatic Inflammation in a Rat Model of Nonalcoholic Steatohepatitis
title_sort dietary iron supplementation alters hepatic inflammation in a rat model of nonalcoholic steatohepatitis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852751/
https://www.ncbi.nlm.nih.gov/pubmed/29401710
http://dx.doi.org/10.3390/nu10020175
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