Fig. 7: Liver Psd3 downregulation in mice fed a NASH-inducing diet reduced liver cholesterol and circulating LDL cholesterol levels and reduced expression of hepatic genes involved in de novo lipogenesis.
From: PSD3 downregulation confers protection against fatty liver disease
C57BL/6 male mice were fed a NASH-inducing diet for a total of 50 weeks and during the last 16 weeks, groups of mice were dosed via once weekly subcutaneous injections with saline (n = 10 animals), control GalNAc–ASO (n = 9 animals, 5 mg per kg body weight per week) or Psd3 GalNAc–ASO (n = 10 animals, 5 mg per kg body weight per week). a–h, Psd3 GalNAc–ASO treatment did not affect body weight gain (a) but reduced liver cholesterol (b) and cholesteryl ester (c), plasma AST (d), total cholesterol (e) and LDL cholesterol levels (f). There were no effects on plasma triglyceride (g) or HDL cholesterol (h) levels. Hepatic mRNA was quantitated by digital gene expression profiling as described in the Methods and expressed as transcripts per million. i–n, Psd3 GalNAc–ASO treatment had no effect on hepatic Srebp1-c (i) but significantly reduced hepatic Acc1 (j), Fasn (k), Scd1 (l), αSma (m) and Ccl2 (n) mRNA expression levels. Data are presented as mean ± s.d. a–h, Two-sided P values were calculated by one-way ANOVA Kruskal–Wallis non-parametric tests followed by Dunn’s multiple comparisons tests. Multiple comparisons were performed by comparing each group with the control group (Ctr GalNAc–ASO). i–n, Two-sided P values were calculated by Mann–Whitney non-parametric tests. TPM, transcripts per million.
