Fig. 3: Muscle-specific deletion of MLL4 enhances glucose tolerance, insulin sensitivity, and reduces liver lipid accumulation primarily through AMPK activation in skeletal muscle. | Nature Communications

Fig. 3: Muscle-specific deletion of MLL4 enhances glucose tolerance, insulin sensitivity, and reduces liver lipid accumulation primarily through AMPK activation in skeletal muscle.

From: Enhancer regulator MLL4 controls skeletal muscle metabolic efficiency by limiting AMPK-mediated fuel catabolism

Fig. 3: Muscle-specific deletion of MLL4 enhances glucose tolerance, insulin sensitivity, and reduces liver lipid accumulation primarily through AMPK activation in skeletal muscle.

a Western blot and quantification of AMPK activation in GC muscles. n = 3 mice per group. P value: 0.0129, 0.0133. b Schematic of MyoAAV-mediated AMPK dominant-negative (DN) overexpression and HFD experiment. c, d Western blot and quantification of p-ACC, t-ACC, p-AMPK, and t-AMPK in GC muscles from MKO mice normalized to WT controls, n = 6 mice per group. P value: <0.0001, 0.0002. e Mouse images after 11 weeks of HFD. f, g Body weight and weight gain, WT-GFP, n = 13; MKO-GFP, n = 12; MKO-AMPK DN, n = 11. f *P value: 0.0003, <0.0001, <0.0001, <0.0001, <0.0001, <0.0001, <0.0001. #P value: 0.013. g *P value: 0.0006, <0.0001, <0.0001, <0.0001, <0.0001, <0.0001. #P value: 0.0248. h iWAT weight, WT-GFP, n = 13; MKO-GFP, n = 12; MKO-AMPK DN, n = 11. *P value: 0.003. #P value: <0.0001. i, j GTT and ITT with AUC analysis, WT-GFP, n = 13; MKO-GFP, n = 12; MKO-AMPK DN, n = 11. i *P value: 0.0003, 0.0011, <0.0001, 0.0001, 0.0035, 0.001. #P value: 0.0226, 0.0306, 0.0182, 0.0119, 0.0331, 0.03. j *P value: 0.0197, 0.0044, 0.0067, 0.0278, 0.0253. #P value: 0.0241, 0.036, 0.0252, 0.0113, 0.0378. k Liver weight, WT-GFP, n = 13; MKO-GFP, n = 12; MKO-AMPK DN, n = 11. *P value: 0.001. #P value: 0.0043. l H&E and Oil Red O staining of liver sections, scale bar = 50 μm, n = 10–13 mice per group. m Liver triglyceride levels, WT-GFP, n = 12; MKO-GFP, n = 11; MKO-AMPK DN, n = 11. *P value: 0.0001. #P value: 0.0015. Data are mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 vs. WT controls, #P < 0.05, ##P < 0.01, ###P < 0.001 vs. GFP controls, n.s. no significance. Statistical analysis performed using two-tailed unpaired Student’s t-test (d), one-way ANOVA (a, h, k, m) with Fisher’s LSD post-hoc test, or two-way ANOVA (f, g, i, j) with a Tukey’s post-hoc test. Source data are provided as a Source data file.

Back to article page