Contrast between cardiac left ventricle and diaphragm muscle in expression of genes involved in carbohydrate and lipid metabolism

Abstract

The heart and diaphragm both need appropriate metabolic machinery to ensure long-term energy supplies, as they must contract rhythmically without cessation for the entire lifetime of the organism to ensure homeostasis of oxygen and carbon dioxide exchange. However, their energy requirements differ due to disparities in mechanical loads. Understanding how these two muscles converge and diverge in their approaches to meeting their metabolic demands may suggest novel strategies for improving cardiac and skeletal muscle long-term performance in health and disease. To assess this at a transcriptional level, expression of genes involved in carbohydrate and lipid metabolism was assessed using microarrays in rats. There were 594 genes with >2-fold differential expression between left ventricle of the heart and diaphragm; 307 were expressed heart>diaphragm and 287 diaphragm>heart. Assignment to gene ontology groups revealed over-representation for "carbohydrate metabolism" (P=0.005, n=32 genes or 5.4% of all genes with differential expression) and "lipid metabolism" (P=0.0012, n=48 genes or 8.1% of all genes with differential expression). For carbohydrate there were 14 genes with heart>diaphragm and 18 genes with diaphragm>heart, and for lipid there were 30 genes with heart>diaphragm and 18 genes with diaphragm>heart. The magnitude of differential expression between heart and diaphragm ranged up to 30-fold for carbohydrate and up to 59-fold for lipid. Carbohydrate-related genes were almost all involved in energy metabolism (e.g. Pfkm, Pgm1, Pgam1, Pfkfb1, Pfkfb2), whereas lipid-related genes were involved in energetics as well as other cellular processes; for both groups this included genes involved in rate-limiting metabolic steps. Data thus indicate that diaphragm and heart have both shared and differential transcriptional strategies for ensuring long-term energy supplies, with a relative favoring of lipid metabolism in the heart and carbohydrate metabolism in the diaphragm.