Prematurity is associated with delayed postnatal activation of mitochondrial oxidative phosphorylation and impaired switch from glycolytic to oxidative metabolism. Fatty acids (FA), which represent a major energy substrate in mature muscle cells, are engaged in the postnatal activation of genes of energy metabolism and lipid oxidation. To understand the mechanism activating mitochondria in human newborns, expression of the genes for mitochondrial uncoupling proteins (UCP) was characterized in autopsy samples of skeletal (n ϭ 28) and cardiac (n ϭ 13) muscles of preterm neonates, who mostly died during the first postnatal month, and two aborted fetuses. Transcripts levels for UCP2, UCP3, and also for genes engaged in the transport of FA between cytoplasm and mitochondria were measured using realtime reverse transcriptase PCR. In accordance with studies in mice, our results document postnatal induction of UCP3 gene expression in skeletal muscle, involvement of nutritional FA in the induction, and a role of UCP3 in mitochondrial FA oxidation. They suggest impaired postnatal activation of UCP3 gene in neonates delivered before approximately 26 wk of gestation. Mean levels of the UCP3 transcript in skeletal muscle were by two orders of magnitude higher than in the heart. In contrast to UCP3, the UCP2 gene was active in fetuses, and its expression was not affected by nutrition. Postnatal switch of glycolytic to oxidative metabolism is of crucial importance for all mammalian neonates. Several studies (1-3) demonstrate the recruitment of energy conversion and ATP synthesis in mitochondria during the early postnatal period as well as insufficient maturation of this mechanism in premature newborns (4, 5). The recruitment of mitochondrial oxidative phosphorylation in the tissues of the newborns reflects changes in the hormonal status and also a shift from glucose to lipids as the major energy source during the early postnatal period (6). However, nutritional FA serve not only as the source of energy but also as modifiers of the gene expression in many tissues (7). The effects of FA on gene expression in the newborns are of great significance with respect to the postnatal maturation of energy metabolism and mitochondrial functions. To understand the mechanisms underlying the adaptation of premature newborns to the extrauterine life, genes engaged in the control of energy metabolism must be identified. The role of the developmental status of the organism and of other possible external factors, such as nutrition, on the expression of the genes must be clarified.UCP represent an important example of developmentally regulated genes participating in the control of mitochondrial energy conversion. They belong to a family of mitochondrial inner membrane transporters and are implicated in the regulation of the proton leak across the membrane. Thus, all UCP may lower the efficiency of mitochondrial ATP production;
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