Fig. 5: LIF downregulates the expression of PPARa via the activation of the STAT3 signaling in hepatic cells.

A LIF overexpression increased the levels of pSTAT3 but not total STAT3 protein or other LIF downstream pathways, including STAT1, STAT4, AKT, ERK, and MAPK in the liver of TgLC mice post TAM injection as determined by Western-blot assays. At least three independent biological replicates were performed. B rLIF treatment (100 ng/ml for 30 min) of primary mouse hepatic cells increased the levels of pSTAT3 but not total STAT3 protein as determined by Western-blot assays. Three replicates were presented in each group. At least three independent biological replicates were performed. C rLIF treatment decreased the mRNA levels of PPARa in primary cultured hepatic cells (n = 4/group). D The sequence and location of a putative STAT3 binding site in the mouse PPARa promoter region. TSS: transcription start site. E rLIF increased the binding of STAT3 to a putative STAT3 binding site in the promoter of PPARa as determined by ChIP assays in primary mouse hepatic cells. A chromatin region without STAT3 binding site was included as a negative control (n = 4/group). F Blocking STAT3 by STAT3 inhibitors, Stattic (2 μM) or Galiellalactone (5 μM), largely abolished the inhibitory effect of rLIF on the expression of PPARa in primary mouse hepatic cells. The mRNA levels of PPARa were determined by qPCR assays and normalized to β-actin (n = 4–8/group). G STAT3 siRNAs largely abolished the inhibitory effect of rLIF on PPARa expression in primary mouse hepatic cells. Left: relative PPARa mRNA levels; right: relative STAT3 mRNA levels in primary cultured hepatic cells (n = 4/group). All data are presented as mean ± SD. Both female and male mice were used. For C, E: two-tailed Student’s t test; for F, G: one-way ANOVA followed by t-test with Tukey’s multiple comparison adjustment. Source data are provided as Source Data file.