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Acetaldehyde Increases Endogenous Adiponectin and Fibrogenesis in Hepatic Stellate Cells But Exogenous Adiponectin Inhibits Fibrogenesis
Author(s) -
Potter James J.,
Mezey Esteban
Publication year - 2007
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2007.00529.x
Subject(s) - hepatic stellate cell , adiponectin , medicine , endocrinology , chemistry , acetaldehyde , adipokine , leptin , microbiology and biotechnology , biology , biochemistry , ethanol , insulin , insulin resistance , obesity
Background: Adiponectin has antifibrogenic properties. Acetaldehyde, the principal metabolite of ethanol, is known to stimulate the expression of type I collagen genes and the production of type I collagen by wild‐type (wt) but not by obese gene ( ob/ob ) stellate cells. The aim of this study was to determine the expression of adiponectin in activated stellate cells obtained from wt and ob/ob mice and to determine the effects of acetaldehyde on adiponectin in relation to the expression of type I collagen. Methods: Stellate cells were isolated from wt and ob/ob mice by perfusion of the portal vein and cultured. Cell adiponectin was visualized by immunohistochemistry and confocal microscopy and determined by radioimmunoassay and by western blot. Adiponectin mRNA and α 1 (I) collagen mRNA were determined by quantitative real time polymerase chain reaction. Results: Adiponectin levels were similar in wt and ob/ob stellate cells. Adiponectin receptor 2 mRNA (AdipoR2 mRNA) and AdipoR2 immunoprotein were higher in ob/ob than in wt stellate cells ( p < 0.01). Acetaldehyde (200 μM) increased adiponectin both in wt and in ob/ob stellate cells ( p < 0.05), but increased AdipoR2 immunoprotein only in ob/ob stellate cells ( p < 0.01). However, in the presence of leptin, acetaldehyde decreased adiponectin in ob/ob stellate cells ( p < 0.01). Acetaldehyde enhanced α 1 (I) collagen mRNA in wt ( p < 0.05), but decreased it in ob/ob stellate cells ( p < 0.01). Leptin abrogated the effect of acetaldehyde in decreasing α 1 (I) collagen mRNA in ob/ob stellate cells ( p < 0.01). Adiponectin inhibited α 1 (I) collagen mRNA in the basal state in wt stellate cells or when enhanced by acetaldehyde. Conclusions: Adiponectin and adiponectin receptor are present in activated stellate cells. Adiponectin has a negative regulatory role on the enhancing effect of acetaldehyde on fibrogenesis in alcoholic liver disease.