Effects of fatty acids on uncoupling protein-2 expression in the rat heart.

Fatty acids are thought to play a role in the activity of uncoupling proteins (UCP) and have been shown to regulate the expression of genes encoding proteins involved in fatty acid handling. Therefore, we investigated whether fatty acids, which are the main substrates for the heart, affect rat cardiac UCP-2 expression in vivo and in vitro. After birth, when the contribution of fatty acid oxidation to cardiac energy conversion increases, UCP-2 expression enhanced rapidly. In the adult heart, however, UCP-2 mRNA levels did not alter during conditions associated with either enhanced (fasting, diabetes) or decreased (hypertrophy) fatty acid utilization. Exposure of neonatal cardiomyocytes and embryonic rat heart-derived H9c2 cells to fatty acids (palmitic and oleic acid) for 48 h strongly induced UCP-2 expression. Stimulation of neonatal cardiomyocytes with triiodothyronine also increased UCP-2 mRNA levels, though only in the presence of fatty acids. Ligands specific to the fatty acid-activated transcription factor PPARalpha, but not to PPARgamma, acted as inducers of cardiomyocyte UCP-2 expression. It is concluded that fatty acids promote UCP-2 expression in neonatal cardiomyocytes, which might explain the rapid increase in UCP-2 mRNA in the postnatal heart. However, UCP-2 mRNA levels in the adult heart appear to be insensitive to changes in cardiac fatty acid handling under various pathological conditions.