Fig. 2 | Nature Communications

Fig. 2

From: An inflammatory-CCRK circuitry drives mTORC1-dependent metabolic and immunosuppressive reprogramming in obesity-associated hepatocellular carcinoma

Fig. 2

Knockdown of Ccrk improves glucose sensitivity, and reduces hepatic lipid accumulation and hepatocarcinogenesis. a Schematic diagram of NASH-HCC mouse model with carcinogen induction (DEN diethylnitrosamine), different diets, and lentivirus-mediated Ccrk knockdown (CD+shCtrl, n = 8; HFHC+shCtrl, n = 15; HFHC+shCcrk, n = 15). b Body weight of mice at 28 weeks. c CCRK protein expression in mouse livers were increased by HFHC at 28 weeks, which could be reduced by shRNA-mediated knockdown. Quantification of CCRK protein levels (relative to β-actin) is shown in a bar chart (right). d Representative pictures of dissected livers (scale bar = 1 cm), and Oil Red O and Ki67 staining of liver tissues in different groups (image magnification = ×200 or ×400, scale bar = 20 μm). e Tumor multiplicity and f tumor sizes were higher in the livers of HFHC-fed mice, which could be reduced by Ccrk knockdown. g, h Dietary obesity-induced CCRK increased lipid accumulation and cell proliferation, which could be abrogated by Ccrk knockdown as shown by Oil Red O staining and Ki67 staining in the livers. i, j Blood triglyceride and NEFA levels were elevated by dietary obesity-induced CCRK at 28 weeks, which could be reduced by Ccrk knockdown. k CCRK over-expression impaired insulin sensitivity in mice. IPGTT was performed on CD-fed and HFHC-fed mice, blood glucose was measured at indicated time points after glucose injection (left), and AUC is shown in a bar chart (right). Data are presented as mean ± SD. *p < 0.05; **p < 0.01; and ***p < 0.001 as calculated by unpaired two-tailed Student’s t-test (b), one-way ANOVA followed by Bonferroni post-hoc test (c, ek), and two-way ANOVA followed by Bonferroni post hoc test (k)

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