Acetaldehyde increases endogenous adiponectin and fibrogenesis in hepatic stellate cells but exogenous adiponectin inhibits fibrogenesis.

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 alpha(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 microM) 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 alpha(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 alpha(1)(I) collagen mRNA in ob/ob stellate cells (p < 0.01). Adiponectin inhibited alpha(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.