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in the adult rodent heart
Division of Cardiology,
* Department of Integrative Biology, and the
Division of Organ Transplantation, University of Texas Houston Medical Center, Houston, Texas 77030, USA
1Correspondence: Division of Cardiology,, University of Texas Houston Medical School, 6431 Fannin, MSB 1.246, Houston, TX 77030, USA. E-mail: ht{at}heart.med.uth.tmc.edu
Relatively little is known concerning the regulation of uncoupling
proteins (UCPs) in the heart. We investigated in the adult rodent heart
1) whether changes in workload, substrate supply, or
cytokine (TNF-
) administration affect UCP-2 and UCP-3 expression,
and 2) whether peroxisome proliferator-activated
receptor (PPAR) regulates the expression of either UCP-2 or
UCP-3. Direct comparisons were made between cardiac and skeletal
muscle. UCP-2, UCP-3, and PPAR expression were reduced when cardiac
workload was either increased (pressure overload by aortic
constriction) or decreased (mechanical unloading by heterotopic
transplantation). Similar results were observed during cytokine
administration. Reduced dietary fatty acid availability resulted in
decreased expression of both cardiac UCP-2 and UCP-3. However, when
fatty acid (the natural ligand for PPAR) supply was increased
(high-fat feeding, fasting, and STZ-induced diabetes), cardiac UCP-3
but not UCP-2 expression increased. Comparable results were observed in
rats treated with the specific PPAR agonist WY-14,643. The level of
cardiac UCP-3 but not UCP-2 expression was severely reduced (20-fold)
in PPAR-/- mice compared to wild-type mice. These
results suggest that in the adult rodent heart, UCP-3 expression is
regulated by PPAR. In contrast, cardiac UCP-2 expression is
regulated in part by a fatty acid-dependent, PPAR-independent
mechanism.—Young, M. E., Patil, S., Ying, J., Depre, C., Ahuja,
H. S., Shipley, G. L., Stepkowski, S. M., Davies,
P. J. A., Taegtmeyer H. Uncoupling protein 3 transcription is
regulated by peroxisome proliferator-activated receptor in the
adult rodent heart.
Key Words: diabetes • fasting • fatty acids • hypertrophy • unloading
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