Fig. 4: Sema can improve myocardial energy production by reducing glycolytic processes and lipid accumulation. | Nature Communications

Fig. 4: Sema can improve myocardial energy production by reducing glycolytic processes and lipid accumulation.

From: Semaglutide ameliorates cardiac remodeling in male mice by optimizing energy substrate utilization through the Creb5/NR4a1 axis

Fig. 4

A Untargeted metabolomics mass spectrometry-based pathway analysis of Sema therapeutic cardiometabolic characteristics, quantification of changes in glycolysis and the TCA products (the red/green boxes represent products that have changed significantly; n = 6); Glucose 6-P: F (2, 15) = 38.02, P = 1.3e-006; Fructose 6-P: F (2, 15) = 23.04, P = 2.7e-005;3-PG: F (2, 15) = 23.58, P = 2.3e-005; PEP: F (2, 15) = 58.41, P = 8.3e-008; Pyruvate: F (2, 15) = 72.71, P = 1.9e-008; Glucose 1-P: F (2, 15) = 24.41, P = 1.9e-005; 6-PG: F (2, 15) = 23.85, P = 2.2e-005; Ribose 5-P: F (2, 15) = 26.35, P = 1.2e-005;Acetyl CoA: F (2, 15) = 206.8 P = 1.2e-011; Citrate: F (2, 15) = 8.599, P = 0.0033; Aconitate: F (2, 15) = 9.583, P = 2.1e-003. B Heatmap showing the determination of the content of free fatty acids associated with untargeted lipid metabolomics (n = 6). C Oil red O staining of NRVMs (scale bar: 50μm/10μm; n = 3 independent experiments with similar results). D The mRNA expression levels of glycolysis and TCA cycle key rate-limiting enzymes HK2, IDH2 and PDH (n = 6); F (4, 30) = 208.2, P = 2.0e-021, F (1.325, 19.87) = 588.5, P = 3.9e-017, F (2, 15) = 38.78, P = 1.2e-006, F (15, 30) = 0.8990, P = 5.7e-001. E The mRNA expression levels of key enzymes associated with fatty acid uptake and transport and mitochondrial β-oxidation CD36, Slc27a1, PDK4, ACOX1 and ACOT1 (n = 6); F (8, 60) = 0.1, P > 9.9e-001, F (3, 41) = 0.3, P = 7.8e-001, F (2, 15) = 426, P = 6.1e-014, F (15, 60) = 0.3, P = 9.9e-001. F Western blot analysis of the glucose transport-associated proteins GLUT1 and GLUT4 and the lipid-associated transporter CD36 (n = 6 independent experiments with similar results). G. GLUT1, GLUT4, and CD36 protein quantification levels were normalized to β-actin (n = 6); CD36/β-actin: F (3, 20) = 27.98, P = 2.3e-007; GLUT1/β-actin: F (3, 20) = 15.61, P = 1.8e-005; GLUT4/β-actin: F (3, 20) = 10.23, P = 2.7e-004. All results are shown as the mean ± SEM, and analysis using one-way ANOVA followed by Bonferroni post hoc test (A, D, E and G) was conducted. p values are indicated. Source data are provided as a Source Data file. TCA, the tricarboxylic acid; NRVMs, neonatal rat ventricular myocytes.

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