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Mitochondrial and energetic cardiac phenotype in hypothyroid rat. Relevance to heart failure.: Hypothyroidism and cardiac energy metabolism

Abstract : Changes in thyroid status are associated with profound alterations in biochemical and physiological functioning of cardiac muscle, although its impact on cardiac energy metabolism is still debated. Similarities between the changes in cardiac gene expression in pathological hypertrophy leading to heart failure, and hypothyroidism prompted scientists to suggest a role for thyroid hormone status in the development of metabolic and functional alterations in this disease. We thus investigated the effects of hypothyroidism on cardiac energy metabolism. Hypothyroid state (HYPO) was induced by thyroidectomy and propyl-thio-uracyl in male rats for three weeks. We examined the effects of hypothyroid state on oxidative capacity and mitochondrial substrate utilization by measuring oxygen consumption of saponin permeabilized cardiac fibers, mitochondrial biogenesis by RT-PCR and energy metabolism and energy transfer enzymes by spectrophotometry. The results show that maximal oxidative capacity of the myocardium was decreased from 24.9°0.9 in control (CT) to 19.3°0.7 µmole O2/min/g dw in HYPO. However, protein content and mRNA of PGC-1Α and mRNA of its transcription cascade that is thought to control mitochondrial content in normal myocardium and heart failure, were unchanged in HYPO. Mitochondrial utilization of glycerol-3P (-70%), malate (-45%) and octanoate (-24%) but not pyruvate was decreased in HYPO. Moreover, the creatine kinase system and energy transfer were hardly affected in HYPO. Besides, hypothyroidism decreased the activation of other signaling pathways like p38 MAPK, AMPK and calcineurin. These results show that cellular hypothyroidism can hardly account for the specific energetic alterations of HF.
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Contributor : Renée Ventura-Clapier <>
Submitted on : Tuesday, June 24, 2008 - 5:21:11 PM
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Yoni Athéa, Anne Garnier, Dominique Fortin, Lahoucine Bahi, Vladimir Veksler, et al.. Mitochondrial and energetic cardiac phenotype in hypothyroid rat. Relevance to heart failure.: Hypothyroidism and cardiac energy metabolism. Pflügers Archiv European Journal of Physiology, Springer Verlag, 2007, 455 ((3)), pp.431-42. ⟨inserm-00290146⟩



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