Fig. 3: Liver WDR6 affects triacylglycerol deposition through regulation of de novo lipogenesis.
From: Upregulation of WDR6 drives hepatic de novo lipogenesis in insulin resistance in mice
a, Heat map of lipid species in livers of AAV-shWDR6 and AAV-shNC mice after CD or HFD feeding for 8 weeks, as determined by lipidomic analysis. n = 4 biologically independent mice per group. b, RT–PCR of representative genes of TAG metabolism in livers of the indicated group. n = 8 biologically independent mice per group. Actb served as a normalization control. c, Liver FASN activity for indicated groups in a. n = 8 biologically independent mice per group. d, Analysis of production of [13C]palmitic acid (converted from d-[U-13C]-glucose) in primary hepatocytes of WDR6-WKO and WT mice. n = 4 biologically independent mice per group. e, PET-CT of shWDR6 and shNC mice. Schematic of the [11C]acetate uptake experiment, which is used to assess the levels of DNL (upper), representative [11C]acetate-PET imaging (lower left) and calculated liver [11C]acetate uptake standard uptake value (SUV; lower right) were obtained. n = 3 biologically independent mice per group. Mouse and syringe icons produced using Servier Medical Art by Servier (https://smart.servier.com/) under a Creative Commons Attribution 3.0 Unported Licence. Image of PET-CT scanner reproduced with permission from MITRO Biotech. f, Lipidomic analyses of the abundance of long-chain FA species in liver of shNC and shWDR6 mice under the CD and HFD states, respectively. n = 4 biologically independent mice per group. g, Western blots of DNL proteins in livers of HFD-fed shWDR6 and shNC mice, with insulin/vehicle treatment, respectively. n = 5 biologically independent mice per group. β-actin serves as the loading control. h, 12-week-old SREBP1c-KO and control mice were injected with Ad-WDR6 or Ad-GFP 15 d before euthanasia. Representative liver ORO staining was obtained. Scale bars, 50 μm. i, Liver TAG levels of the mice described in h. n = 8 biologically independent mice per group. j, FASN protein levels in liver of the mice described in h. n = 4 biologically independent mice per group. β-actin served as the loading control. Experiments in a–j were performed using male mice. Data in b, c, f, g, i and j are presented as the mean ± s.d., determined by two-way ANOVA and Tukey’s multiple-comparisons test. Data in d and e are presented as the mean ± s.d., determined by unpaired two-sided Student’s t-test.
