Leptin deficiency prevents the activation of the murine α2(I) collagen promoter by acetaldehyde

Leptin enhances hepatic fibrosis induced experimentally by various agents. The influence of leptin deficiency on murine α2(I) collagen promoter activation by acetaldehyde and by TGFβ1 was investigated. Acetaldehyde failed to activate the promoter in ob/ob stellate cells as compared to its activating effect in wild-type cells. By contrast, TGFβ1 increased the activity of the promoter in the ob/ob and wild-type cells. Total cell TGFβ1 and secretion of total and free TGFβ1 were lower in cultured stellate cells from ob/ob mice than wild-type mice. Acetaldehyde increased free cell TGFβ1 and secretion of total and free TGFβ1 in wild-type, but not in ob/ob cells. The lack of activation of the α2(I) collagen promoter by acetaldehyde in association with a lack of increase in TGFβ1 in response to acetaldehyde in ob/ob stellate cells provides further evidence for a mediating role of TGFβ1 in the actions of acetaldehyde on collagen transcription.