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. 2020 Sep 25;11(2):597–621. doi: 10.1016/j.jcmgh.2020.09.012

Figure 4.

Figure 4

TTP loss in vivo restrains steatosis development, inflammation, and fibrosis induced by MCD diet. (A) ZFP36 levels of human NAFLD and NASH patients of GEO Datasets. Data are represented as means ± SD of fold change vs control. The t test for comparison of 2 groups was used. Adjusted P value based on t test with Benjamini, Krieger and Yekutieli correction for multiple comparisons (Q = 5%). (B) Zfp36 expression in livers of ob/ob (n = 6 per group) mice vs control (CTL). (C) Zfp36 expression in livers of db/db (n = 5 per group) mice vs control CTL. (D) Zfp36 levels in GEO Datasets of mice models of NAFLD and NASH. Data are represented as means ± SD of fold change vs control. (E) Scheme of experimental protocol used to fed mice fed with MCD diet. Two- to 3-month-old LTTPKO and FLX littermates were fed with control or MCD diet for 2 weeks. (FLX CTL, n = 4; LTTPKO CTL, n = 3; FLX MCD, n = 4; LTTPKO MCD, n = 7). (F) Mouse body weight (g) during 2 weeks of MCD diet feeding (D, day). (G) Liver weight vs body weight of FLX and LTTPKO mice after 2 weeks of MCD diet feeding. (H) Representative livers anatomies and histologic liver sections stained with Picro Sirius red of FLX and LTTPKO mice fed with normal or MCD diet for 2 weeks. (I) Quantifications of liver parenchymal lipid droplets content (steatosis) and fibrosis (Picro Sirius red staining) in mice fed with normal or MCD diet for 2 weeks. Lipid droplets density and intensity of Picro Sirius red staining was assessed by 2 independent investigators (- no steatosis/fibrosis staining, + weak, ++ moderate, +++ strong steatosis/fibrosis) and reported as percentage of animal per each group. (J) Triglyceride measurement in livers of FLX and LTTPKO mice fed with normal or MCD diet for 2 weeks. (K) mRNA expression of inflammatory markers, fibrotic markers, EMT markers, and Fgf-21 in livers of FLX (n = 4) and LTTPKO (n = 7) mice fed with normal or MCD diet for 2 weeks. Data represent mean ± SD. The t test for comparison of 2 groups was used. (L) Representative Western blot and quantification of IL6 protein levels in FLX and LTTPKO mice fed with MCD diet for 2 weeks. Tubulin was used as loading control. (M) Representative F4/80 staining of FLX and LTTPKO mice fed with normal or MCD diet. (N) Quantification of F4/80 staining as % of all mice per group. Intensity was assessed by 2 independent investigators using a staining scale (- no staining, + weak, ++ moderate, +++ strong staining). ∗∗∗P < .001, ∗∗P < .01, ∗P < .05.