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Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
1Correspondence: Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, P.O. Box 616, 6200 MD Maastricht, the Netherlands. E-mail: Karin.vdLee{at}FYS.Unimaas.NL
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 PPAR
, but not to PPAR
, 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.—van der Lee, K. A. J. M., Willemsen,
P. H. M., van der Vusse, G. J., van Bilsen, M. Effects
of fatty acids on uncoupling protein-2 expression in the rat heart.
Key Words: cardiomyocytes • metabolism • UCP • gene expression
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