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.