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Substitution in Amino Acid 70 of Hepatitis C Virus Core Protein Changes the Adipokine Profile via Toll-Like Receptor 2/4 Signaling

BACKGROUND & AIMS: It has been suggested that amino acid (aa) substitution at position 70 from arginine (70R) to glutamine (70Q) in the genotype 1b hepatitis C virus (HCV) core protein is associated with insulin resistance and worse prognosis. However, the precise mechanism is still unclear. The...

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Autores principales: Uraki, Satoko, Tameda, Masahiko, Sugimoto, Kazushi, Shiraki, Katsuya, Takei, Yoshiyuki, Nobori, Tsutomu, Ito, Masaaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487891/
https://www.ncbi.nlm.nih.gov/pubmed/26121241
http://dx.doi.org/10.1371/journal.pone.0131346
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author Uraki, Satoko
Tameda, Masahiko
Sugimoto, Kazushi
Shiraki, Katsuya
Takei, Yoshiyuki
Nobori, Tsutomu
Ito, Masaaki
author_facet Uraki, Satoko
Tameda, Masahiko
Sugimoto, Kazushi
Shiraki, Katsuya
Takei, Yoshiyuki
Nobori, Tsutomu
Ito, Masaaki
author_sort Uraki, Satoko
collection PubMed
description BACKGROUND & AIMS: It has been suggested that amino acid (aa) substitution at position 70 from arginine (70R) to glutamine (70Q) in the genotype 1b hepatitis C virus (HCV) core protein is associated with insulin resistance and worse prognosis. However, the precise mechanism is still unclear. The aim of this study was to investigate the impact of the substitution at position 70 in HCV core protein on adipokine production by murine and human adipocytes. METHODS: The influence of treatment with HCV core protein (70R or 70Q) on adipokine production by both 3T3-L1 and human adipocytes were examined with real-time PCR and enzyme-linked immunosorbent assay (ELISA), and triglyceride content was also analyzed. The effects of toll-like receptor (TLR)2/4 inhibition on IL-6 production by 3T3-L1 induced by HCV core protein were examined. RESULTS: IL-6 production was significantly increased and adiponectin production was reduced without a change in triglyceride content by treatment with 70Q compared to 70R core protein in both murine and human adipocytes. IL-6 induction of 3T3-L1 cells treated by 70Q HCV core protein was significantly inhibited with anti-TLR2 antibody by 42%, and by TLR4 inhibitor by 40%. CONCLUSIONS: Our study suggests that extracellular HCV core protein with substitution at position 70 enhanced IL-6 production and reduced adiponectin production from visceral adipose tissue, which can cause insulin resistance, hepatic steatosis, and ultimately development of HCC.
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spelling pubmed-44878912015-07-02 Substitution in Amino Acid 70 of Hepatitis C Virus Core Protein Changes the Adipokine Profile via Toll-Like Receptor 2/4 Signaling Uraki, Satoko Tameda, Masahiko Sugimoto, Kazushi Shiraki, Katsuya Takei, Yoshiyuki Nobori, Tsutomu Ito, Masaaki PLoS One Research Article BACKGROUND & AIMS: It has been suggested that amino acid (aa) substitution at position 70 from arginine (70R) to glutamine (70Q) in the genotype 1b hepatitis C virus (HCV) core protein is associated with insulin resistance and worse prognosis. However, the precise mechanism is still unclear. The aim of this study was to investigate the impact of the substitution at position 70 in HCV core protein on adipokine production by murine and human adipocytes. METHODS: The influence of treatment with HCV core protein (70R or 70Q) on adipokine production by both 3T3-L1 and human adipocytes were examined with real-time PCR and enzyme-linked immunosorbent assay (ELISA), and triglyceride content was also analyzed. The effects of toll-like receptor (TLR)2/4 inhibition on IL-6 production by 3T3-L1 induced by HCV core protein were examined. RESULTS: IL-6 production was significantly increased and adiponectin production was reduced without a change in triglyceride content by treatment with 70Q compared to 70R core protein in both murine and human adipocytes. IL-6 induction of 3T3-L1 cells treated by 70Q HCV core protein was significantly inhibited with anti-TLR2 antibody by 42%, and by TLR4 inhibitor by 40%. CONCLUSIONS: Our study suggests that extracellular HCV core protein with substitution at position 70 enhanced IL-6 production and reduced adiponectin production from visceral adipose tissue, which can cause insulin resistance, hepatic steatosis, and ultimately development of HCC. Public Library of Science 2015-06-29 /pmc/articles/PMC4487891/ /pubmed/26121241 http://dx.doi.org/10.1371/journal.pone.0131346 Text en © 2015 Uraki et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Uraki, Satoko
Tameda, Masahiko
Sugimoto, Kazushi
Shiraki, Katsuya
Takei, Yoshiyuki
Nobori, Tsutomu
Ito, Masaaki
Substitution in Amino Acid 70 of Hepatitis C Virus Core Protein Changes the Adipokine Profile via Toll-Like Receptor 2/4 Signaling
title Substitution in Amino Acid 70 of Hepatitis C Virus Core Protein Changes the Adipokine Profile via Toll-Like Receptor 2/4 Signaling
title_full Substitution in Amino Acid 70 of Hepatitis C Virus Core Protein Changes the Adipokine Profile via Toll-Like Receptor 2/4 Signaling
title_fullStr Substitution in Amino Acid 70 of Hepatitis C Virus Core Protein Changes the Adipokine Profile via Toll-Like Receptor 2/4 Signaling
title_full_unstemmed Substitution in Amino Acid 70 of Hepatitis C Virus Core Protein Changes the Adipokine Profile via Toll-Like Receptor 2/4 Signaling
title_short Substitution in Amino Acid 70 of Hepatitis C Virus Core Protein Changes the Adipokine Profile via Toll-Like Receptor 2/4 Signaling
title_sort substitution in amino acid 70 of hepatitis c virus core protein changes the adipokine profile via toll-like receptor 2/4 signaling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487891/
https://www.ncbi.nlm.nih.gov/pubmed/26121241
http://dx.doi.org/10.1371/journal.pone.0131346
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