5 years ago

Hepatic microvascular dysfunction and increased advanced glycation end products are components of non-alcoholic fatty liver disease

Karine Lino Rodrigues, Evelyn Nunes Goulart da Silva Pereira, Marcelo Pelajo Machado, Eduardo Tibiriça, Cassiano F. Gonçalves-de-Albuquerque, Rosiane Aparecida Miranda, Hugo Caire de Castro Faria-Neto, Igor José da Silva, Isalira Peroba Ramos, Anissa Daliry, Carmen Cabanelas Pazos-Moura, Edgar Eduardo Ilaquita Flores, Raquel Rangel Silvares

by Evelyn Nunes Goulart da Silva Pereira, Raquel Rangel Silvares, Edgar Eduardo Ilaquita Flores, Karine Lino Rodrigues, Isalira Peroba Ramos, Igor José da Silva, Marcelo Pelajo Machado, Rosiane Aparecida Miranda, Carmen Cabanelas Pazos-Moura, Cassiano F. Gonçalves-de-Albuquerque, Hugo Caire de Castro Faria-Neto, Eduardo Tibiriça, Anissa Daliry


This study aimed to investigate the pathophysiology of hepatic microcirculatory dysfunction in non-alcoholic fatty liver disease (NAFLD).


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.


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.


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.

Publisher URL: http://journals.plos.org/plosone/article

DOI: 10.1371/journal.pone.0179654

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.