Leptin Inhibits PPARgamma Gene Expression in Hepatic Stellate Cells in the Mouse Model of Liver Damage

Hepatic stellate cell (HSC) activation is a key cellular event in the development of liver fibrosis. Peroxisome proliferator-activated receptor-gamma (PPARgamma) has been shown to function as a key transcription regulator linked to suppressing HSC activation. Compelling evidence indicates that leptin plays a unique role in the development of liver fibrosis. The aim of this study is to investigate the in vivo impact of leptin on PPARgamma expression in HSCs in the model of TAA-induced liver damage. The results of the present study provide the first in vivo evidence that leptin might exert an inhibitory effect on PPARgamma protein expression in HSCs, which is mediated at least through leptin-induced ERK1/2 activation. Long-form leptin receptor is involved in leptin-induced ERK1/2 activation and the subsequent decline in PPARgamma expression in HSCs in the model. Furthermore, the inhibitory effect of leptin on PPARgamma protein expression enhances HSC activation and proliferation in this model. The in vivo findings from this report might provide additional insights into the mechanisms underlying the profibrogenic action of leptin in liver.