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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #163950
Title: EVIDENCE FOR MITOCHONDRIAL THIOESTERASE 1 IS A PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-ALPHA-REGULATED GENE IN CARDIAC AND SKELETAL MUSCLE

Author
item STAVINOHA, MELISSA - UT HEALTH SCI CENTER
item RAYSPELLICY, JOSEPH - UT HEALTH SCI CENTER
item ESSOP, M - UNIV OF CAPE TOWN
item GRAVELEAU, CHRISTOPHE - UNIV OF UTAH
item ABEL, E - UNIV OF UTAH
item HART-SAILORS, MARY - UT HEALTH SCI CENTER
item Mersmann, Harry
item BRAY, MOLLY - UT HEALTH SCI CENTER
item YOUNG, MARTIN - UT HEALTH SCI CENTER

Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/26/2004
Publication Date: 11/1/2004
Citation: Stavinoha, M.A., RaySpellicy, J.W., Essop, M.F., Graveleau, C., Abel, E.D., Hart-Sailors, M.L., Mersmann, H.J., Bray, M.S., Young, M.E. 2004. Evidence for mitochondrial thioesterase 1 as a peroxisome proliferator-activated receptor-alpha-regulated gene in cardiac and skeletal muscle. 287(5):E888-E895.

Interpretive Summary: The enzyme, mitochondrial thioesterase may be involved with fatty acid utilization, an important source of energy to all mammals. We hypothesized that this thioesterase is regulated by PPARalpha and that its gene would be expressed to different degrees at different times of the day to coincide with the blood levels of fatty acids. In rats, the heart thioesterase gene only varied modestly (1.4 times) over the 24 hour day/night cycle. The skeletal muscle thioesterase gene varied less than the heart gene. The expression of the thioesterase gene was increased when the fatty acids were elevated by high-fat diets, by fasting, by diabetes, or by increasing PPARalpha; the greatest increases were in the dark in both heart and skeletal muscle. We conclude that this thioesterase is regulated by PPARalpha. The thioesterase is increased in both heart and skeletal muscle by conditions that increase blood fatty acids. The data suggest that thioesterase has a role in the utilization of fatty acids in both muscles.

Technical Abstract: 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-alpha (PPAR alpha)-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 alpha-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 alpha activity, and muscle FAO rates, increased mte1 mRNA in heart and soleus muscle. Conversely, pressure overload and hypoxia, interventions that decrease cardiac PPAR alpha activity and FAO rates, repressed cardiac mte1 expression. Specific activation of PPAR alpha 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 alpha-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 alpha-regulated gene in cardiac and skeletal muscle.