Figure 3. LXR agonist AZ876 significantly alters cardiac lipid composition toward a higher content in polyunsaturated fatty acids.

A, Partial least squares discriminant analysis (PLS‐DA) of the cardiac lipid profile between the 4 groups, x‐axis, principal component 1 (Comp1); y‐axis, principal component 2 (Comp2), ellipses show 95% CI. B, Heatmap of 33 significantly regulated cardiac lipid species (VEH vs AZ876). Mice were treated with either CTRL or AZ876 supplementation and received 4 consecutive subcutaneous injections of either VEH or ISO. Clustering and heat map were created with MetaboAnalyst. Clustering of normalized intensities represented as z‐scores, 2‐way ANOVA, followed by Benjamini‐Hochberg P value adjustment (P<0.05). C, Proposed beneficial lipid species containing monounsaturated FAs and the omega‐3 fatty acid docosahexaenoic acid (FA 22:6 n‐3, DHA). D, Log2‐fold change of significantly altered FA moieties compared with CTRL_VEH. Values less than zero on the y‐axis indicate lower fatty acid content, values greater than 1 indicate increase. The bubble size represents the measured intensity, which is analogous to the abundance of the FA. The intensities are normalized, and batch corrected. The FAs are sorted according to the degree of saturation. 2‐way ANOVA followed by a Benjamini‐Hochberg P value adjustment (P<0.05). Stearic acid, oleic acid, and docosahexaenoic acid are shown in magnification. Data presented as mean ± SEM, n=10–12 per group, *=P<0.05, ***=P<0.01, ****=P<0.0001, 1‐way (D) or 2‐way ANOVA (C) with Bonferroni post hoc test. AZ876 indicates LXR agonist AZ876; CTRL, control (diet); ELOVL5, fatty acid elongase 5; FA, fatty acid; FADS2, fatty acid desaturase 2; ISO, isoproterenol; LPC, lysophosphatidyl‐choline; MUFA, monounsaturated fatty acids; LPG, lysophosphatidylglycerol; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PUFA, polyunsaturated fatty acids; SCD2, stearoyl‐CoA desaturase 2; SFA, saturated fatty acids; and VEH, vehicle (NaCl).