TY - JOUR
T1 - Sex-specific skeletal muscle fatigability and decreased mitochondrial oxidative capacity in adult rats exposed to postnatal hyperoxia
AU - Tetri, Laura H.
AU - Diffee, Gary M.
AU - Barton, Gregory P.
AU - Braun, Rudolf K.
AU - Yoder, Hannah E.
AU - Haraldsdottir, Kristin
AU - Eldridge, Marlowe W.
AU - Goss, Kara N.
N1 - Publisher Copyright:
© 2018 Tetri, Diffee, Barton, Braun, Yoder, Haraldsdottir, Eldridge and Goss.
PY - 2018/3/29
Y1 - 2018/3/29
N2 - Premature birth affects more than 10% of live births, and is characterized by relative hyperoxia exposure in an immature host. Long-term consequences of preterm birth include decreased aerobic capacity, decreased muscular strength and endurance, and increased prevalence of metabolic diseases such as type 2 diabetes mellitus. Postnatal hyperoxia exposure in rodents is a well-established model of chronic lung disease of prematurity, and also recapitulates the pulmonary vascular, cardiovascular, and renal phenotype of premature birth. The objective of this study was to evaluate whether postnatal hyperoxia exposure in rats could recapitulate the skeletal and metabolic phenotype of premature birth, and to characterize the subcellular metabolic changes associated with postnatal hyperoxia exposure, with a secondary aim to evaluate sex differences in this model. Compared to control rats, male rats exposed to 14 days of postnatal hyperoxia then aged to 1 year demonstrated higher skeletal muscle fatigability, lower muscle mitochondrial oxidative capacity, more mitochondrial damage, and higher glycolytic enzyme expression. These differences were not present in female rats with the same postnatal hyperoxia exposure. This study demonstrates detrimental mitochondrial and muscular outcomes in the adult male rat exposed to postnatal hyperoxia. Given that young adults born premature also demonstrate skeletal muscle dysfunction, future studies are merited to determine whether this dysfunction as well as reduced aerobic capacity is due to reduced mitochondrial oxidative capacity and metabolic dysfunction.
AB - Premature birth affects more than 10% of live births, and is characterized by relative hyperoxia exposure in an immature host. Long-term consequences of preterm birth include decreased aerobic capacity, decreased muscular strength and endurance, and increased prevalence of metabolic diseases such as type 2 diabetes mellitus. Postnatal hyperoxia exposure in rodents is a well-established model of chronic lung disease of prematurity, and also recapitulates the pulmonary vascular, cardiovascular, and renal phenotype of premature birth. The objective of this study was to evaluate whether postnatal hyperoxia exposure in rats could recapitulate the skeletal and metabolic phenotype of premature birth, and to characterize the subcellular metabolic changes associated with postnatal hyperoxia exposure, with a secondary aim to evaluate sex differences in this model. Compared to control rats, male rats exposed to 14 days of postnatal hyperoxia then aged to 1 year demonstrated higher skeletal muscle fatigability, lower muscle mitochondrial oxidative capacity, more mitochondrial damage, and higher glycolytic enzyme expression. These differences were not present in female rats with the same postnatal hyperoxia exposure. This study demonstrates detrimental mitochondrial and muscular outcomes in the adult male rat exposed to postnatal hyperoxia. Given that young adults born premature also demonstrate skeletal muscle dysfunction, future studies are merited to determine whether this dysfunction as well as reduced aerobic capacity is due to reduced mitochondrial oxidative capacity and metabolic dysfunction.
KW - Mitochondria
KW - Preterm birth
KW - Sex differences
KW - Skeletal muscle
KW - Skeletal muscle metabolism
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U2 - 10.3389/fphys.2018.00326
DO - 10.3389/fphys.2018.00326
M3 - Article
C2 - 29651255
AN - SCOPUS:85044868928
SN - 1664-042X
VL - 9
JO - Frontiers in Physiology
JF - Frontiers in Physiology
IS - MAR
M1 - 326
ER -