Uncoupling protein 3 transcription is regulated by peroxisome proliferator-activated receptor (alpha) in the adult rodent heart.
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-alpha) administration affect UCP-2 and UCP-3 expression, and 2) whether peroxisome proliferator-activated receptor alpha (PPARalpha) regulates the expression of either UCP-2 or UCP-3. Direct comparisons were made between cardiac and skeletal muscle. UCP-2, UCP-3, and PPARalpha 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 PPARalpha) 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 PPARalpha agonist WY-14,643. The level of cardiac UCP-3 but not UCP-2 expression was severely reduced (20-fold) in PPARalpha-/- mice compared to wild-type mice. These results suggest that in the adult rodent heart, UCP-3 expression is regulated by PPARalpha. In contrast, cardiac UCP-2 expression is regulated in part by a fatty acid-dependent, PPARalpha-independent mechanism.
Division of Cardiology, Department of Integrative Biology, University of Texas Houston Medical Center, Houston, Texas 77030, USA.
M E
ME
Young
S
S
Patil
J
J
Ying
C
C
Depre
H S
HS
Ahuja
G L
GL
Shipley
S M
SM
Stepkowski
P J
PJ
Davies
H
H
Taegtmeyer
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology; D005508:Food Deprivation; D006321:Heart / Q000187:drug effects / Q000502:physiology; D016027:Heart Transplantation; D007473:Ion Channels; D008297:Male; D026901:Membrane Transport Proteins; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D012313:RNA / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014475:Uncoupling Agents; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D014655:Vascular Resistance
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D004041:Dietary Fats; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D011743:Pyrimidines; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C000604390:Ucp2 protein, mouse; C000604391:Ucp2 protein, rat; C000604393:Ucp3 protein, mouse; C000604394:Ucp3 protein, rat; D014475:Uncoupling Agents; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D012313:RNA; C006253:pirinixic acid