Fig. 7: WDR6 may be a potential therapeutic target for hepatic steatosis.
From: Upregulation of WDR6 drives hepatic de novo lipogenesis in insulin resistance in mice
a, Representative western blots of phospho-PPP1CB (Thr316), WDR6 and FASN in human liver samples. n = 20 independent samples. b–d, Scatter diagram of the correlation of WDR6 and liver TAG levels (b), WDR6 and FASN levels (c), FASN and liver TAG levels (d) in human liver tissues. n = 20 independent samples. e, Left: MD simulation of the interaction of PPP1CB (blue) and superimposition of WDR6 with (yellow) or without (pink) coupling XLIX. Right: the Cα of key amino acids (Arg347 in black, Arg345 in red) with displacement change when binding XLIX. Black dashed lines indicate the distances between Cα atoms. f, Detailed interactions of WDR6 binding in PPP1CB. Black dashed box indicates the binding pocket of PPP1CB. g, Representative ORO staining of liver sections in XLIX and vehicle groups. Scale bars, 50 μm. h, Liver TAG levels of mice described in g, n = 10 biologically independent mice per group. i, Western blots of phospho-PPP1CB (Thr316) and FASN protein levels in livers of the mice described in g; n = 6 biologically independent mice per group. β-actin served as the loading control. j, Mice with HFHC or NC feeding were treated with XLIX or vehicle. Representative ORO staining of liver tissue is shown. Scale bars, 50 μm. k, TAG levels of the liver tissue described in j. n = 7 and 6 biologically independent mice in HFHC and NC groups, respectively. l, RT–PCR of representative genes of pro-inflammatory and profibrotic genes in the liver tissue described in j. n = 6 biologically independent mice per group. Actb served as the normalization control. m, Western blots of phospho-PPP1CB (Thr316) in the liver tissue described in j. n = 5 biologically independent mice per group. n, Representative ORO staining of liver sections in WDR6-LKI or LC given XLIX or vehicle. Scale bars, 50 μm. o, Liver TAG levels described in n. n = 7 biologically independent mice in LC group and 8 biologically independent mice in WDR6-LKI group. Experiments in j–o were performed using male mice. Data in b–d were analysed by linear regression and Pearson correlation coefficient (two-sided test). Data in h and i are presented as the mean ± s.d., determined by unpaired two-sided Student’s t-test. Data in k–m and o are presented as the mean ± s.d., determined by two-way ANOVA and Tukey’s multiple-comparisons test. For western blots, β-actin served as the loading control. TAG levels were normalized to the protein content of the relevant sample.
