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Publication : Fasting reduces liver fibrosis in a mouse model for chronic cholangiopathies.

First Author  Sokolović A Year  2013
Journal  Biochim Biophys Acta Volume  1832
Issue  10 Pages  1482-91
PubMed ID  23707514 Mgi Jnum  J:202509
Mgi Id  MGI:5519198 Doi  10.1016/j.bbadis.2013.05.012
Citation  Sokolovic A, et al. (2013) Fasting reduces liver fibrosis in a mouse model for chronic cholangiopathies. Biochim Biophys Acta 1832(10):1482-91
abstractText  Chronic cholangiopathies often lead to fibrosis, as a result of a perpetuated wound healing response, characterized by increased inflammation and excessive deposition of proteins of the extracellular matrix. Our previous studies have shown that food deprivation suppresses the immune response, which led us to postulate its beneficial effects on pathology in liver fibrosis driven by portal inflammation. We investigated the consequences of fasting on liver fibrosis in Abcb4(-/-) mice that spontaneously develop it due to a lack of phospholipids in bile. The effect of up to 48h of food deprivation was studied by gene expression profiling, (immuno)histochemistry, and biochemical assessments of biliary output, and hepatic and plasma lipid composition. In contrast to increased biliary output in the wild type counterparts, bile composition in Abcb4(-/-) mice remained unchanged with fasting and did not influence the attenuation of fibrosis. Markers of inflammation, however, dramatically decreased in livers of Abcb4(-/-) mice already after 12h of fasting. Reduced presence of activated hepatic stellate cells and actively increased tissue remodeling further propelled a decrease in parenchymal fibrosis in fasting. This study is the first to show that food deprivation positively influences liver pathology in a fibrotic mouse model for chronic cholangiopathies, opening a door for new strategies to improve liver regeneration in chronic disease.
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