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-regulated gene in cardiac and skeletal muscle
1Brown Foundation Institute of Molecular Medicine and 2School of Public Health, Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas 77030; 3Hatter Institute for Cardiology Research, University of Cape Town Faculty of Health Sciences, Cape Town 7925, South Africa; 4Division of Endocrinology, Metabolism and Diabetes, University of Utah, Salt Lake City, Utah 84112; and 5United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030
Submitted 30 April 2004 ; accepted in final form 26 July 2004
The physiological role of mitochondrial thioesterase 1 (MTE1) is unknown. It was proposed that MTE1 promotes fatty acid (FA) oxidation (FAO) by acting in concert with uncoupling protein (UCP)3. We previously showed that ucp3 is a peroxisome proliferator-activated receptor-
(PPAR)-regulated gene, allowing induction when FA availability increases. On the assumption that UCP3 and MTE1 act in partnership to increase FAO, we hypothesized that mte1 is also a PPAR-regulated gene in cardiac and skeletal muscle. Using real-time RT-PCR, we characterized mte1 gene expression in rat heart and soleus muscles. Messenger RNA encoding for mte1 was 3.2-fold higher in heart than in soleus muscle. Cardiac mte1 mRNA exhibited modest diurnal variation, with 1.4-fold higher levels during dark phase. In contrast, skeletal muscle mte1 mRNA remained relatively constant over the course of the day. High-fat feeding, fasting, and streptozotocin-induced diabetes, interventions that increase FA availability, muscle PPAR activity, and muscle FAO rates, increased mte1 mRNA in heart and soleus muscle. Conversely, pressure overload and hypoxia, interventions that decrease cardiac PPAR activity and FAO rates, repressed cardiac mte1 expression. Specific activation of PPAR in vivo through WY-14643 administration rapidly induced mte1 mRNA in cardiac and skeletal muscle. WY-14643 also induced mte1 mRNA in isolated adult rat cardiomyocytes dose dependently. Expression of mte1 was markedly lower in hearts and soleus muscles isolated from PPAR-null mice. Alterations in cardiac and skeletal muscle ucp3 expression mirrored that of mte1 in all models investigated. In conclusion, mte1, like ucp3, is a PPAR-regulated gene in cardiac and skeletal muscle.
nonesterified fatty acids; uncoupling protein 3; diurnal variations; diabetes; fasting
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