Fig. 3: Liver specific deletion of SAPS3 is sufficient to improve the systemic response to high fat diet. | Nature Communications

Fig. 3: Liver specific deletion of SAPS3 is sufficient to improve the systemic response to high fat diet.

From: SAPS3 subunit of protein phosphatase 6 is an AMPK inhibitor and controls metabolic homeostasis upon dietary challenge in male mice

Fig. 3

a Schematic showing of the generation of SAPS3 liver specific knockout mice. b 8 weeks old male FF and LKO mice were fed with CD or HFD (32.5 kcal% fat) for 16 weeks (FF, ppp6r3 fl/fl mice; LKO, SAPS3 liver specific knockout mice). Bodyweight was measured. Mean ± s.d., CD n = 8 mice per group; HFD n = 10 mice per group analyzed by one-way ANOVA, ****p < 0.0001. The SAPS3 protein expression in the liver was tested by Western blotting. The results are representative of three independent experiments. c Fat mass and lean mass composition of mice under HFD were measured by echo-MRI every 4 weeks. Mean ± s.d., n = 6 mice per group analyzed by two-tailed t-test. Fat mass, week: 4, *p = 0.042; 8, **p = 0.009; 12, **p = 0.005; 16, **p = 0.002. Lean mass, week: 8, *p = 0.039; 12, **p = 0.006; 16, **p = 0.009. d Liver weight was compared. Mean ± s.d., CD n = 8 mice per group; HFD n = 10 mice per group analyzed by two-tailed t-test, *p = 0.026; ***p = 0.0006; n.s., not significant. e Representative pictures of livers, H&E staining and quantification of liver samples after H&E staining. Scale bar, 100 µm. Mean ± s.d., n = 3 mice per group analyzed by two-tailed t-test, ***p = 0.0003; n.s., not significant. f Serum triglyceride level was measured. Mean ± s.d., CD n = 7 mice per group; HFD n = 10 mice per group analyzed by two-tailed t-test. FF (CD/HFD), **p = 0.007; HFD (FF/LKO), **p = 0.009; n.s., not significant. g Fasting blood glucose level was measured. Mean ± s.d., CD n = 7 mice per group; HFD n = 10 mice per group analyzed by two-tailed t-test. FF (CD/HFD), ***p = 0.0004; HFD (FF/LKO), ***p = 0.0008; n.s., not significant. h Glucose tolerance test and insulin tolerance test were performed at the endpoint. Mean ± s.d., CD n = 7 mice per group; HFD n = 10 mice per group analyzed by one-way ANOVA. GTT, ****p < 0.0001; ITT, ***p = 0.0005. i The concentration of C-peptide was compared between groups. Mean ± s.d., CD n = 7 mice per group; HFD n = 10 mice per group analyzed by two-tailed t-test, **p = 0.008; n.s., not significant. j Liver samples were collected from FF and LKO mice under CD and HFD. Tissue lysates were analyzed by Western blotting. The results are representative of two independent experiments.

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