Leptin deficiency prevents the activation of the murine alpaha 2(I) collagen promoter by acetaldehyde.Arch Biochem Biophys. 2004 Jun 01; 426(1):73-7.AB
Leptin enhances hepatic fibrosis induced experimentally by various agents. The influence of leptin deficiency on murine alpha 2(I) collagen promoter activation by acetaldehyde and by TGF beta 1 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, TGF beta 1 increased the activity of the promoter in the ob/ob and wild-type cells. Total cell TGF beta 1 and secretion of total and free TGF beta 1 were lower in cultured stellate cells from ob/ob mice than wild-type mice. Acetaldehyde increased free cell TGF beta1 and secretion of total and free TGF beta 1 in wild-type, but not in ob/ob cells. The lack of activation of the alpha 2(I) collagen promoter by acetaldehyde in association with a lack of increase in TGF beta 1 in response to acetaldehyde in ob/ob stellate cells provides further evidence for a mediating role of TGF beta 1 in the actions of acetaldehyde on collagen transcription.