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Non-alcoholic fatty liver disease combined with rheumatoid arthritis exacerbates liver fibrosis by stimulating co-localization of PTRF and TLR4 in rats

Rheumatoid arthritis (RA) has a high prevalence in patients with non-alcoholic fatty liver disease (NAFLD); however, the underlying mechanism is unclear. To address this, our study established a rat model with both NAFLD and RA by feeding a high-fat diet (HFD) and administering intradermal injection...

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Autores principales: Zhang, Shengpeng, Zhu, Peng, Yuan, Jianan, Cheng, Kunming, Xu, Qixiang, Chen, Wei, Pan, Zui, Zheng, Yongqiu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10279862/
https://www.ncbi.nlm.nih.gov/pubmed/37346294
http://dx.doi.org/10.3389/fphar.2023.1149665
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author Zhang, Shengpeng
Zhu, Peng
Yuan, Jianan
Cheng, Kunming
Xu, Qixiang
Chen, Wei
Pan, Zui
Zheng, Yongqiu
author_facet Zhang, Shengpeng
Zhu, Peng
Yuan, Jianan
Cheng, Kunming
Xu, Qixiang
Chen, Wei
Pan, Zui
Zheng, Yongqiu
author_sort Zhang, Shengpeng
collection PubMed
description Rheumatoid arthritis (RA) has a high prevalence in patients with non-alcoholic fatty liver disease (NAFLD); however, the underlying mechanism is unclear. To address this, our study established a rat model with both NAFLD and RA by feeding a high-fat diet (HFD) and administering intradermal injection of Freund’s complete adjuvant (FCA) with bovine type II collagen. Collagen-induced RA (CIA) was confirmed by hind paw swelling and histological examination. The histomorphological characteristics of NAFLD were evaluated by Masson’s trichrome and hematoxylin-eosin staining. The development of NAFLD was further evaluated by measuring serum concentrations of triglyceride (TG), total cholesterol (T-CHO), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lipopolysaccharide (LPS). The results showed that HFD feeding exacerbated secondary inflammation in CIA rats, whereas FCA/bovine type II collagen injection increased serum levels of ALT, AST, TG, T-CHO, and LPS and exacerbated hepatic fibrosis in both normal and NAFLD rats. Interestingly, NAFLD + CIA significantly promoted the expression of PTRF, a caveolae structure protein involved in hepatic lipid metabolism and affecting downstream signaling of Toll-like receptor 4 (TLR4) and PI3K/Akt activation. High resolution confocal microscopy revealed increased PTRF and TLR4 co-localization in hepatic small vessels of NAFLD + CIA rats. AAV9-mediated PTRF knockdown inhibited TLR4 signaling and alleviated hepatic fibrosis in NAFLD + CIA rats. Together, these findings indicate that NAFLD combined with CIA causes synovial injury and enhances non-alcoholic fatty liver fibrosis in rats. PTRF could attenuate the symptoms of NAFLD + CIA likely by affecting TLR4/PTRF co-expression and downstream signaling.
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spelling pubmed-102798622023-06-21 Non-alcoholic fatty liver disease combined with rheumatoid arthritis exacerbates liver fibrosis by stimulating co-localization of PTRF and TLR4 in rats Zhang, Shengpeng Zhu, Peng Yuan, Jianan Cheng, Kunming Xu, Qixiang Chen, Wei Pan, Zui Zheng, Yongqiu Front Pharmacol Pharmacology Rheumatoid arthritis (RA) has a high prevalence in patients with non-alcoholic fatty liver disease (NAFLD); however, the underlying mechanism is unclear. To address this, our study established a rat model with both NAFLD and RA by feeding a high-fat diet (HFD) and administering intradermal injection of Freund’s complete adjuvant (FCA) with bovine type II collagen. Collagen-induced RA (CIA) was confirmed by hind paw swelling and histological examination. The histomorphological characteristics of NAFLD were evaluated by Masson’s trichrome and hematoxylin-eosin staining. The development of NAFLD was further evaluated by measuring serum concentrations of triglyceride (TG), total cholesterol (T-CHO), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lipopolysaccharide (LPS). The results showed that HFD feeding exacerbated secondary inflammation in CIA rats, whereas FCA/bovine type II collagen injection increased serum levels of ALT, AST, TG, T-CHO, and LPS and exacerbated hepatic fibrosis in both normal and NAFLD rats. Interestingly, NAFLD + CIA significantly promoted the expression of PTRF, a caveolae structure protein involved in hepatic lipid metabolism and affecting downstream signaling of Toll-like receptor 4 (TLR4) and PI3K/Akt activation. High resolution confocal microscopy revealed increased PTRF and TLR4 co-localization in hepatic small vessels of NAFLD + CIA rats. AAV9-mediated PTRF knockdown inhibited TLR4 signaling and alleviated hepatic fibrosis in NAFLD + CIA rats. Together, these findings indicate that NAFLD combined with CIA causes synovial injury and enhances non-alcoholic fatty liver fibrosis in rats. PTRF could attenuate the symptoms of NAFLD + CIA likely by affecting TLR4/PTRF co-expression and downstream signaling. Frontiers Media S.A. 2023-06-06 /pmc/articles/PMC10279862/ /pubmed/37346294 http://dx.doi.org/10.3389/fphar.2023.1149665 Text en Copyright © 2023 Zhang, Zhu, Yuan, Cheng, Xu, Chen, Pan and Zheng. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Zhang, Shengpeng
Zhu, Peng
Yuan, Jianan
Cheng, Kunming
Xu, Qixiang
Chen, Wei
Pan, Zui
Zheng, Yongqiu
Non-alcoholic fatty liver disease combined with rheumatoid arthritis exacerbates liver fibrosis by stimulating co-localization of PTRF and TLR4 in rats
title Non-alcoholic fatty liver disease combined with rheumatoid arthritis exacerbates liver fibrosis by stimulating co-localization of PTRF and TLR4 in rats
title_full Non-alcoholic fatty liver disease combined with rheumatoid arthritis exacerbates liver fibrosis by stimulating co-localization of PTRF and TLR4 in rats
title_fullStr Non-alcoholic fatty liver disease combined with rheumatoid arthritis exacerbates liver fibrosis by stimulating co-localization of PTRF and TLR4 in rats
title_full_unstemmed Non-alcoholic fatty liver disease combined with rheumatoid arthritis exacerbates liver fibrosis by stimulating co-localization of PTRF and TLR4 in rats
title_short Non-alcoholic fatty liver disease combined with rheumatoid arthritis exacerbates liver fibrosis by stimulating co-localization of PTRF and TLR4 in rats
title_sort non-alcoholic fatty liver disease combined with rheumatoid arthritis exacerbates liver fibrosis by stimulating co-localization of ptrf and tlr4 in rats
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10279862/
https://www.ncbi.nlm.nih.gov/pubmed/37346294
http://dx.doi.org/10.3389/fphar.2023.1149665
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