Effects of EGFR inhibition on hepatic lipid metabolism in HFD-fed mice.

(A) Analysis of proteins in the EGFR signaling pathway in mouse liver tissues. The figure shows the total and phosphorylated forms of EGFR and Akt. (B) Analysis of proteins associated with de novo lipogenesis in mouse liver tissues. (C–E) Real time quantitative PCR showing the transcriptional levels of genes related to lipid and cholesterol metabolism. (C) Transcriptional levels of cholesterol biosynthesis-related genes in liver tissues. (D) Transcriptional levels of de novo lipogenesis-related genes in liver tissues. (E) Transcriptional levels of fatty acid β-oxidation-related genes in liver tissues. (F) Huh-7 cells were treated with EGF and gefitinib. The expression of proteins in the EGFR signaling pathway were measured in Huh-7 cells. Real-time quantitative PCR assay showing the transcriptional levels of lipid metabolism-related genes. (G) Huh-7 cells were treated with palmitic acid (PA) and gefitinib. Representative images of oil Red O staining of Huh-7 cells and the transcriptional levels of lipid metabolism-related genes, as examined by real-time quantitative PCR. NCD, NCD-fed mice (NCD, black bars); HFD, untreated HFD-fed mice (white bars); HFD+PD, HFD-fed mice treated with PD153035 (gray bars); NC, negative control; EGF, Huh-7 cells stimulated with 10 ng/mL EGF; EGF+G, Huh-7 cells stimulated with 10 ng/mL EGF and 10 μM gefitinib; PA, Huh-7 cells incubated with 400 μM palmitic acid; PA+G, Huh-7 cells incubated with 400 μM palmitic acid and 10 μM gefitinib for 24 h. Data are expressed as the mean ± SEM. * P P P P P P < 0.0001 HFD vs. HFD+PD group.