Cargando…
Hepatic microvascular dysfunction and increased advanced glycation end products are components of non-alcoholic fatty liver disease
BACKGROUND: This study aimed to investigate the pathophysiology of hepatic microcirculatory dysfunction in non-alcoholic fatty liver disease (NAFLD). METHODS: In Wistar rats, NAFLD model was induced by 20 weeks of high-fat diet (HFD) feeding. Rolling and adhesion of leukocytes and tissue perfusion i...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5476253/ https://www.ncbi.nlm.nih.gov/pubmed/28628674 http://dx.doi.org/10.1371/journal.pone.0179654 |
_version_ | 1783244577462812672 |
---|---|
author | Pereira, Evelyn Nunes Goulart da Silva Silvares, Raquel Rangel Flores, Edgar Eduardo Ilaquita Rodrigues, Karine Lino Ramos, Isalira Peroba da Silva, Igor José Machado, Marcelo Pelajo Miranda, Rosiane Aparecida Pazos-Moura, Carmen Cabanelas Gonçalves-de-Albuquerque, Cassiano F. Faria-Neto, Hugo Caire de Castro Tibiriça, Eduardo Daliry, Anissa |
author_facet | Pereira, Evelyn Nunes Goulart da Silva Silvares, Raquel Rangel Flores, Edgar Eduardo Ilaquita Rodrigues, Karine Lino Ramos, Isalira Peroba da Silva, Igor José Machado, Marcelo Pelajo Miranda, Rosiane Aparecida Pazos-Moura, Carmen Cabanelas Gonçalves-de-Albuquerque, Cassiano F. Faria-Neto, Hugo Caire de Castro Tibiriça, Eduardo Daliry, Anissa |
author_sort | Pereira, Evelyn Nunes Goulart da Silva |
collection | PubMed |
description | BACKGROUND: This study aimed to investigate the pathophysiology of hepatic microcirculatory dysfunction in non-alcoholic fatty liver disease (NAFLD). METHODS: In Wistar rats, NAFLD model was induced by 20 weeks of high-fat diet (HFD) feeding. Rolling and adhesion of leukocytes and tissue perfusion in hepatic microcirculation were examined using in vivo microscopic and laser speckle contrast imaging (LSCI), respectively. Oxidative stress and inflamatory parameters were analysed by TBARs, catalase enzyme activity, RT-PCR and ELISA. The participation of advanced glycation end-products (AGE) and its receptor RAGE was evaluated by the measurement of gene and protein expression of RAGE by RT-PCR and Western-blot, respectively and by liver and serum quantification of fluorescent AGEs. RESULTS: Wistar rats fed high-fat diet (HFD) showed increase in epididymal and abdominal fat content, systolic arterial blood pressure, fasting blood glucose levels, hepatic triglycerides and cholesterol, and impairment of glucose and insulin metabolisms. Liver histology confirmed the presence of steatosis and ultrasound analysis revealed increased liver size and parenchymal echogenicity in HFD-fed rats. HFD causes significant increases in leukocyte rolling and adhesion on hepatic microcirculation and decrease in liver microvascular blood flow. Liver tissue presented increase in oxidative stress and inflammtion. At 20 weeks, there was a significantly increase in AGE content in the liver and serum of HFD-fed rats and an increase in RAGE gene expression in the liver. CONCLUSION: The increase in liver AGE levels and microcirculatory disturbances could play a role in the pathogenesis of liver injury and are key components of NAFLD. |
format | Online Article Text |
id | pubmed-5476253 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-54762532017-07-03 Hepatic microvascular dysfunction and increased advanced glycation end products are components of non-alcoholic fatty liver disease Pereira, Evelyn Nunes Goulart da Silva Silvares, Raquel Rangel Flores, Edgar Eduardo Ilaquita Rodrigues, Karine Lino Ramos, Isalira Peroba da Silva, Igor José Machado, Marcelo Pelajo Miranda, Rosiane Aparecida Pazos-Moura, Carmen Cabanelas Gonçalves-de-Albuquerque, Cassiano F. Faria-Neto, Hugo Caire de Castro Tibiriça, Eduardo Daliry, Anissa PLoS One Research Article BACKGROUND: This study aimed to investigate the pathophysiology of hepatic microcirculatory dysfunction in non-alcoholic fatty liver disease (NAFLD). METHODS: In Wistar rats, NAFLD model was induced by 20 weeks of high-fat diet (HFD) feeding. Rolling and adhesion of leukocytes and tissue perfusion in hepatic microcirculation were examined using in vivo microscopic and laser speckle contrast imaging (LSCI), respectively. Oxidative stress and inflamatory parameters were analysed by TBARs, catalase enzyme activity, RT-PCR and ELISA. The participation of advanced glycation end-products (AGE) and its receptor RAGE was evaluated by the measurement of gene and protein expression of RAGE by RT-PCR and Western-blot, respectively and by liver and serum quantification of fluorescent AGEs. RESULTS: Wistar rats fed high-fat diet (HFD) showed increase in epididymal and abdominal fat content, systolic arterial blood pressure, fasting blood glucose levels, hepatic triglycerides and cholesterol, and impairment of glucose and insulin metabolisms. Liver histology confirmed the presence of steatosis and ultrasound analysis revealed increased liver size and parenchymal echogenicity in HFD-fed rats. HFD causes significant increases in leukocyte rolling and adhesion on hepatic microcirculation and decrease in liver microvascular blood flow. Liver tissue presented increase in oxidative stress and inflammtion. At 20 weeks, there was a significantly increase in AGE content in the liver and serum of HFD-fed rats and an increase in RAGE gene expression in the liver. CONCLUSION: The increase in liver AGE levels and microcirculatory disturbances could play a role in the pathogenesis of liver injury and are key components of NAFLD. Public Library of Science 2017-06-19 /pmc/articles/PMC5476253/ /pubmed/28628674 http://dx.doi.org/10.1371/journal.pone.0179654 Text en © 2017 Pereira 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Pereira, Evelyn Nunes Goulart da Silva Silvares, Raquel Rangel Flores, Edgar Eduardo Ilaquita Rodrigues, Karine Lino Ramos, Isalira Peroba da Silva, Igor José Machado, Marcelo Pelajo Miranda, Rosiane Aparecida Pazos-Moura, Carmen Cabanelas Gonçalves-de-Albuquerque, Cassiano F. Faria-Neto, Hugo Caire de Castro Tibiriça, Eduardo Daliry, Anissa Hepatic microvascular dysfunction and increased advanced glycation end products are components of non-alcoholic fatty liver disease |
title | Hepatic microvascular dysfunction and increased advanced glycation end products are components of non-alcoholic fatty liver disease |
title_full | Hepatic microvascular dysfunction and increased advanced glycation end products are components of non-alcoholic fatty liver disease |
title_fullStr | Hepatic microvascular dysfunction and increased advanced glycation end products are components of non-alcoholic fatty liver disease |
title_full_unstemmed | Hepatic microvascular dysfunction and increased advanced glycation end products are components of non-alcoholic fatty liver disease |
title_short | Hepatic microvascular dysfunction and increased advanced glycation end products are components of non-alcoholic fatty liver disease |
title_sort | hepatic microvascular dysfunction and increased advanced glycation end products are components of non-alcoholic fatty liver disease |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5476253/ https://www.ncbi.nlm.nih.gov/pubmed/28628674 http://dx.doi.org/10.1371/journal.pone.0179654 |
work_keys_str_mv | AT pereiraevelynnunesgoulartdasilva hepaticmicrovasculardysfunctionandincreasedadvancedglycationendproductsarecomponentsofnonalcoholicfattyliverdisease AT silvaresraquelrangel hepaticmicrovasculardysfunctionandincreasedadvancedglycationendproductsarecomponentsofnonalcoholicfattyliverdisease AT floresedgareduardoilaquita hepaticmicrovasculardysfunctionandincreasedadvancedglycationendproductsarecomponentsofnonalcoholicfattyliverdisease AT rodrigueskarinelino hepaticmicrovasculardysfunctionandincreasedadvancedglycationendproductsarecomponentsofnonalcoholicfattyliverdisease AT ramosisaliraperoba hepaticmicrovasculardysfunctionandincreasedadvancedglycationendproductsarecomponentsofnonalcoholicfattyliverdisease AT dasilvaigorjose hepaticmicrovasculardysfunctionandincreasedadvancedglycationendproductsarecomponentsofnonalcoholicfattyliverdisease AT machadomarcelopelajo hepaticmicrovasculardysfunctionandincreasedadvancedglycationendproductsarecomponentsofnonalcoholicfattyliverdisease AT mirandarosianeaparecida hepaticmicrovasculardysfunctionandincreasedadvancedglycationendproductsarecomponentsofnonalcoholicfattyliverdisease AT pazosmouracarmencabanelas hepaticmicrovasculardysfunctionandincreasedadvancedglycationendproductsarecomponentsofnonalcoholicfattyliverdisease AT goncalvesdealbuquerquecassianof hepaticmicrovasculardysfunctionandincreasedadvancedglycationendproductsarecomponentsofnonalcoholicfattyliverdisease AT farianetohugocairedecastro hepaticmicrovasculardysfunctionandincreasedadvancedglycationendproductsarecomponentsofnonalcoholicfattyliverdisease AT tibiricaeduardo hepaticmicrovasculardysfunctionandincreasedadvancedglycationendproductsarecomponentsofnonalcoholicfattyliverdisease AT daliryanissa hepaticmicrovasculardysfunctionandincreasedadvancedglycationendproductsarecomponentsofnonalcoholicfattyliverdisease |