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Hepatic microvascular dysfunction and increased advanced glycation end products are components of non-alcoholic fatty liver disease
- Source :
- PLoS ONE, Vol 12, Iss 6, p e0179654 (2017), PLoS ONE
- Publication Year :
- 2017
- Publisher :
- Public Library of Science (PLoS), 2017.
-
Abstract
- 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.
- Subjects :
- Blood Glucose
Glycation End Products, Advanced
Male
0301 basic medicine
Steatosis
Physiology
medicine.medical_treatment
Interleukin-1beta
Receptor for Advanced Glycation End Products
lcsh:Medicine
Blood Pressure
Pathology and Laboratory Medicine
Cardiovascular Physiology
medicine.disease_cause
Biochemistry
Cytopathology
Fats
White Blood Cells
chemistry.chemical_compound
0302 clinical medicine
Non-alcoholic Fatty Liver Disease
Animal Cells
Glycation
Leukocytes
Medicine and Health Sciences
lcsh:Science
Immune Response
Liver injury
Multidisciplinary
Liver Diseases
Fatty liver
Catalase
Lipids
Cholesterol
Liver
Blood Circulation
030211 gastroenterology & hepatology
Cellular Types
Research Article
medicine.medical_specialty
Immune Cells
Immunology
Gastroenterology and Hepatology
Diet, High-Fat
Real-Time Polymerase Chain Reaction
Microcirculation
03 medical and health sciences
Signs and Symptoms
Diagnostic Medicine
Internal medicine
medicine
Animals
Rats, Wistar
Triglycerides
Nutrition
Inflammation
Blood Cells
Tumor Necrosis Factor-alpha
business.industry
Insulin
lcsh:R
Biology and Life Sciences
nutritional and metabolic diseases
Cell Biology
medicine.disease
Rats
Diet
Fatty Liver
Oxidative Stress
030104 developmental biology
Endocrinology
chemistry
Anatomical Pathology
lcsh:Q
business
Oxidative stress
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 12
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....10ea794e27934a6edab1e45ae948c01e