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 protei ns (UCP) and have been shown to regulate the expression of genes encoding p roteins involved in fatty acid handling. Therefore, we investigated whether fatty acids, which are the main substrates for the heart, affect rat cardi ac UCP-2 expression in vivo and in vitro. After birth, when the contributio n of fatty acid oxidation to cardiac energy conversion increases, UCP-2 exp ression enhanced rapidly. In the adult heart, however, UCP-2 mRNA levels di d not alter during conditions associated with either enhanced (fasting, dia betes) or decreased (hypertrophy) fatty acid utilization. Exposure of neona tal cardiomyocytes and embryonic rat heart-derived H9c2 cells to fatty acid s (palmitic and oleic acid) for 48 h strongly induced UCP-2 expression. Sti mulation of neonatal cardiomyocytes with triiodothyronine also increased UC P-2 mRNA levels, though only in the presence of fatty acids. Ligands specif ic to the fatty acid-activated transcription factor PPAR alpha, but not to PPAR gamma, acted as inducers of cardiomyocyte UCP-2 expression. It is conc luded that fatty acids promote UCP-2 expression in neonatal cardiomyocytes, which might explain the rapid increase in UCP-2 mRNA in the postnatal hear t. However, UCP-2 mRNA levels in the adult heart appear to be insensitive t o changes in cardiac fatty acid handling under various pathological conditi ons.