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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...

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Detalles Bibliográficos
Autores principales: 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
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
Descripción
Sumario: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.