Transcriptional regulation of metabolic processes: implications for cardiac metabolism

Under normal conditions the oxidation of fatty acids and glucose covers, respectively, approximately 65% and 30% of the energy demand of the beating heart. Evidence is accumulating that various pathophysiological conditions are associated with overt changes in cardiac energy metabolism. For instance, in diabetes cardiac energy conversion relies even more on fatty acid than on glucose oxidation. In contrast, during cardiac hypertrophy the opposite takes place, i.e. the utilization of carbohydrates increases at the expense of lipids. The mechanisms responsible for and the significance of these metabolic adaptations are largely unknown. A growing body of evidence indicates that these metabolic adaptations are brought about, at least in part, through adjustments in the rate of transcription of genes encoding proteins involved in substrate transport and metabolism. There are reasons to believe that the transcriptional regulation of these "metabolic genes" is subject to modulation by metabolites per se, i.e. by oxygen, glucose and fatty acids. In this review the concept of metabolic remodelling as an important facet of cardiac adaptation to chronic pathophysiological conditions is introduced and the putative roles of metabolites in transcriptional regulation in the heart are considered.