Abstract P3055: Combined Metabolomic And Transcriptomic Profiling Approaches Reveal The Cardiac Response To High-fat Diet

Abstract

The response of vital organs to different types of nutrition or diet is a fundamental question in physiology. It is unclear how different diets can alter cardiac metabolism and function. We examined the cardiac response to 4 weeks of high-fat diet in adult mice, measuring cardiac metabolites and mRNA. Metabolomics showed dramatic differences after high-fat diet, including increases in several acyl-carnitine species. The RNAseq data showed changes consistent with adaptations to use more fatty acid as substrate and an increase in the anti-oxidant protein catalase. Changes in mRNA were correlated to changes in protein level for several highly responsive genes, including catalase and HMGcs2. We also found significant sex differences in both metabolomics and RNAseq datasets, both at baseline and after high fat diet. This work reveals the response of a vital organ to dietary intervention at both metabolomic and transcriptomic levels, which is a fundamental question in physiology that may have relevance for cardiovascular diseases. This work also reveals significant sex differences in cardiac metabolites and gene expression. Figure 1: Metabolomic changes after HFD; electron microscopy shows changes in mitochondrial morphology. A. Principal component analysis (loading) of metabolites demonstrates that the first two principal components (PC) cluster the samples into 4 groups. PC1 + PC2 account for 85.47% of the proportion of variance in this metabolomic dataset.B. Graph of acyl-carnitine species, dots with lines indicated mean +/- SEM. “C#” refers to the number of carbon atoms in the lipid, that is C16 is palmitoylcarnitine, C14 is myristoylcarnitine, etc. N= 10 hearts for each group. The comparison of control (chow) to HFD is highly statistically significant by 2-way ANOVA, p<0.0001.C. Representative examples of electron microscopy from cardiac ventricular samples.D. Graphs of average mitochondrial area (um 2 ) and average number of mitochondria per high-power image. N= 4 hearts for each group, * indicates significantly different by t-test.