Galectin-3 ablation protects mice from diet-induced NASH: A major scavenging role for galectin-3 in liver

Autor: Iacobini, Carla, Menini, Stefano, Ricci, Carlo, Blasetti Fantauzzi, C., BLASETTI FANTAUZZI, Claudia, Angela, Scipioni, Salvi, Laura, Cordone, Samantha, Francesca, Delucchi, Matteo, Serino, Massimo, Federici, Flavia, Pricci, Pugliese, Giuseppe
Rok vydání: 2011
Předmět:
CD36 Antigens
Liver Cirrhosis
Galectin 3
Receptor for Advanced Glycation End Products
Apoptosis
Inbred C57BL
medicine.disease_cause
Severity of Illness Index
Mice
Non-alcoholic Fatty Liver Disease
Immunologic
Fibrosis
Receptors
steatosis
Leukocytes
Receptors
Immunologic
Settore MED/49 - Scienze Tecniche Dietetiche Applicate
advanced lipoxidation endproducts
Beta oxidation
Mice
Knockout
Chemistry
Atherogenic
medicine.anatomical_structure
Liver
Galectin-3
Hepatocyte
Female
medicine.symptom
medicine.medical_specialty
Knockout
Inflammation
Internal medicine
medicine
Animals
Gene Silencing
Antigens
Hepatology
fibrosis
Lipid metabolism
inflammation
oxidative stress
Fibroblasts
Lipid Metabolism
medicine.disease
Diet
Mice
Inbred C57BL
Fatty Liver
Antigens
CD36
Diet
Atherogenic
Oxidative Stress
Endocrinology
Steatosis
CD36
Oxidative stress
Zdroj: Journal of Hepatology. 54:975-983
ISSN: 0168-8278
DOI: 10.1016/j.jhep.2010.09.020
Popis: Excess fatty acid oxidation and generation of reactive carbonyls with formation of advanced lipoxidation endproducts (ALEs) is involved in nonalcoholic steatohepatitis (NASH) by triggering inflammation, hepatocyte injury, and fibrosis. This study aimed at verifying the hypothesis that ablation of the ALE-receptor galectin-3 prevents experimental NASH by reducing receptor-mediated ALE clearance and downstream events.Galectin-3-deficient (Lgals3(-/-)) and wild type (Lgals3(+/+)) mice received an atherogenic diet or standard chow for 8 months. Liver tissue was analyzed for morphology, inflammation, cell and matrix turnover, lipid metabolism, ALEs, and ALE-receptors.Steatosis was significantly less pronounced in Lgals3(-/-) than Lgals3(+/+) animals on atherogenic diet. NASH, invariably detected in Lgals3(+/+) mice, was observed, to a lower extent, only in 3/8 Lgals3(-/-) mice, showing less inflammatory, degenerative, and fibrotic phenomena than Lgals3(+/+) mice. This was associated with higher circulating ALE levels and lower tissue ALE accumulation and expression of other ALE-receptors. Up-regulation of hepatic fatty acid synthesis and oxidation, inflammatory cell infiltration, pro-inflammatory cytokines, endoplasmic reticulum stress, hepatocyte apoptosis, myofibroblast transdifferentiation, and impaired Akt phosphorylation were also significantly attenuated in Lgals3(-/-) animals. Galectin-3 silencing in liver endothelial cells resulted in reduced N(ε)-carboxymethyllysine-modified albumin uptake and ALE-receptor expression.Galectin-3 ablation protects from diet-induced NASH by decreasing hepatic ALE accumulation, with attenuation of inflammation, hepatocyte injury, and fibrosis. It also reduced up-regulation of lipid synthesis and oxidation causing less fat deposition, oxidative stress, and possibly insulin resistance. These data suggest that galectin-3 is a major receptor involved in ALE uptake by the liver.
Databáze: OpenAIRE
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