FIGURE 5.

Inhibition of fatty acid oxidation partially improves metabolic reserve and cardiac function in Bscl2^cKO mice. (A) 6‐month‐old male Cre−;Bscl2^f/f (Ctrl) and Bscl2^cKO (cKO) mice received daily i.p. injection with PBS or trimetazidine (TMZ) at 15 mg/kg body weights (BW) for a total of 6 weeks. (B) Ratio of ventricle weight (VW) to tibia length (TL). Ctrl, n = 5; cKO, n = 9. (C) Left ventricular internal diameter in end systole (LVIDs); (D) ejection fraction and (E) fractional shortening. PBS‐Ctrl, n = 10; PBS‐cKO, n = 9. n = 9 per TMZ‐treated group. (F) Heatmap of major lipid species based on Z‐score calculated from the summed ion abundances normalised to milligram of wet tissue; (G and H) comparison of the total normalised ion abundances for (G) glycerolipids as well as (H) NEFA and ACs. n = 3 per PBS‐treated group. n = 4 per TMZ‐treated group. Each sample was pooled from three animals. (I) Ventricular glycogen. PBS‐Ctrl, n = 5; PBS‐cKO, n = 9. n = 9 per TMZ‐treated group. (J) Ventricular ATP contents normalised to gram of wet tissue. PBS‐Ctrl, n = 5; PBS‐cKO, n = 8. TMZ‐Ctrl, n = 5, TMZ‐cKO, n = 9. (K) Representative Western blotting and quantification of total cell extracts from ventricles of 6‐month‐old PBS and TMZ‐treated Ctrl and Bscl2^cKO mice. n = 6 per group. Data were normalised to GAPDH with PBS‐treated Ctrl set to 1. Two independent experiments. (L) qRT‐PCR analysis of lipid and glucose transport genes and cardiac stress genes in ventricles of 6‐month‐old PBS and TMZ‐treated male mice. n = 6 per group. *, p < .05; **, p < .005. ns: not significant. Two‐way ANOVA followed by Tukey's post‐hoc tests