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Consistent with reduced expression of Cpt1b, the levels of various acyl-carnitine molecules were significantly diminished in the KO heart tissue (Figure?2F; Table S3). In addition, reduced expression of the enzymes in the TCA cycle coincided with accumulation of the corresponding see more upstream intermediates in the KO samples (Figure?2G; Table S3). This includes citrate and?cis-aconitate upstream of Idh3g and succinate upstream of Sdhc. Interestingly, KO hearts also exhibited a significant increase in the levels of ceramides, which have been implicated in cardiomyopathy and cardiac failure (Table S3; Park and Goldberg, 2012). Thus, the combined transcriptomics and metabolomics data strongly suggest that NELF supports the high demand of energy production in cardiomyocytes through sustained metabolic gene expression. Gene ontology analysis of the gene expression profile indicates a significant enrichment of genes involved Vasopressin Receptor in the PPAR-regulated pathways (data not shown). Among the several PPAR family members, PPAR�� plays an especially important role in orchestrating the cardiac transcription program required for high-capacity energy production in cardiomyocytes (Gigu��re, 2008?and?Madrazo and Kelly, 2008). Comparing the gene expression profile of the NELF-B KO with previously published microarray data from PPAR�� KO myocardium ( Georgiadi et?al., 2012), we found that these two KO mouse models?shared a substantial overlap in selleck chemical downregulated target genes (p?
