Dimming the Powerhouse: Mitochondrial Dysfunction in the Liver and Skeletal Muscle of Intrauterine Growth Restricted Fetuses
Intrauterine growth restriction (IUGR) of the fetus, resulting from placental insufficiency (PI), is characterized by low fetal oxygen and nutrient concentrations that stunt growth rates of metabolic organs. Numerous animal models of IUGR recapitulate pathophysiological conditions found in human fet...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2021.612888/full |
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| author | Alexander L. Pendleton Stephanie R. Wesolowski Timothy R. H. Regnault Ronald M. Lynch Sean W. Limesand |
| author_facet | Alexander L. Pendleton Stephanie R. Wesolowski Timothy R. H. Regnault Ronald M. Lynch Sean W. Limesand |
| author_sort | Alexander L. Pendleton |
| collection | DOAJ |
| description | Intrauterine growth restriction (IUGR) of the fetus, resulting from placental insufficiency (PI), is characterized by low fetal oxygen and nutrient concentrations that stunt growth rates of metabolic organs. Numerous animal models of IUGR recapitulate pathophysiological conditions found in human fetuses with IUGR. These models provide insight into metabolic dysfunction in skeletal muscle and liver. For example, cellular energy production and metabolic rate are decreased in the skeletal muscle and liver of IUGR fetuses. These metabolic adaptations demonstrate that fundamental processes in mitochondria, such as substrate utilization and oxidative phosphorylation, are tempered in response to low oxygen and nutrient availability. As a central metabolic organelle, mitochondria coordinate cellular metabolism by coupling oxygen consumption to substrate utilization in concert with tissue energy demand and accretion. In IUGR fetuses, reducing mitochondrial metabolic capacity in response to nutrient restriction is advantageous to ensure fetal survival. If permanent, however, these adaptations may predispose IUGR fetuses toward metabolic diseases throughout life. Furthermore, these mitochondrial defects may underscore developmental programming that results in the sequela of metabolic pathologies. In this review, we examine how reduced nutrient availability in IUGR fetuses impacts skeletal muscle and liver substrate catabolism, and discuss how enzymatic processes governing mitochondrial function, such as the tricarboxylic acid cycle and electron transport chain, are regulated. Understanding how deficiencies in oxygen and substrate metabolism in response to placental restriction regulate skeletal muscle and liver metabolism is essential given the importance of these tissues in the development of later lifer metabolic dysfunction. |
| first_indexed | 2024-12-21T09:35:29Z |
| format | Article |
| id | doaj.art-fb182e110b44438d8eb08377868b43c6 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-21T09:35:29Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-fb182e110b44438d8eb08377868b43c62022-12-21T19:08:39ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-05-011210.3389/fendo.2021.612888612888Dimming the Powerhouse: Mitochondrial Dysfunction in the Liver and Skeletal Muscle of Intrauterine Growth Restricted FetusesAlexander L. Pendleton0Stephanie R. Wesolowski1Timothy R. H. Regnault2Ronald M. Lynch3Sean W. Limesand4School of Animal and Comparative Biomedical Sciences, The University of Arizona, Tucson, AZ, United StatesDepartment of Pediatrics, University of Colorado School of Medicine, Aurora, CO, United StatesDepartment of Physiology and Pharmacology, Western University, London, ON, CanadaSchool of Animal and Comparative Biomedical Sciences, The University of Arizona, Tucson, AZ, United StatesSchool of Animal and Comparative Biomedical Sciences, The University of Arizona, Tucson, AZ, United StatesIntrauterine growth restriction (IUGR) of the fetus, resulting from placental insufficiency (PI), is characterized by low fetal oxygen and nutrient concentrations that stunt growth rates of metabolic organs. Numerous animal models of IUGR recapitulate pathophysiological conditions found in human fetuses with IUGR. These models provide insight into metabolic dysfunction in skeletal muscle and liver. For example, cellular energy production and metabolic rate are decreased in the skeletal muscle and liver of IUGR fetuses. These metabolic adaptations demonstrate that fundamental processes in mitochondria, such as substrate utilization and oxidative phosphorylation, are tempered in response to low oxygen and nutrient availability. As a central metabolic organelle, mitochondria coordinate cellular metabolism by coupling oxygen consumption to substrate utilization in concert with tissue energy demand and accretion. In IUGR fetuses, reducing mitochondrial metabolic capacity in response to nutrient restriction is advantageous to ensure fetal survival. If permanent, however, these adaptations may predispose IUGR fetuses toward metabolic diseases throughout life. Furthermore, these mitochondrial defects may underscore developmental programming that results in the sequela of metabolic pathologies. In this review, we examine how reduced nutrient availability in IUGR fetuses impacts skeletal muscle and liver substrate catabolism, and discuss how enzymatic processes governing mitochondrial function, such as the tricarboxylic acid cycle and electron transport chain, are regulated. Understanding how deficiencies in oxygen and substrate metabolism in response to placental restriction regulate skeletal muscle and liver metabolism is essential given the importance of these tissues in the development of later lifer metabolic dysfunction.https://www.frontiersin.org/articles/10.3389/fendo.2021.612888/fullmitochondrial metabolismtricarboxylic acid (TCA) cycleintrauterine growth restriction (IUGR)placental insufficiencyoxidative phosphorylation |
| spellingShingle | Alexander L. Pendleton Stephanie R. Wesolowski Timothy R. H. Regnault Ronald M. Lynch Sean W. Limesand Dimming the Powerhouse: Mitochondrial Dysfunction in the Liver and Skeletal Muscle of Intrauterine Growth Restricted Fetuses Frontiers in Endocrinology mitochondrial metabolism tricarboxylic acid (TCA) cycle intrauterine growth restriction (IUGR) placental insufficiency oxidative phosphorylation |
| title | Dimming the Powerhouse: Mitochondrial Dysfunction in the Liver and Skeletal Muscle of Intrauterine Growth Restricted Fetuses |
| title_full | Dimming the Powerhouse: Mitochondrial Dysfunction in the Liver and Skeletal Muscle of Intrauterine Growth Restricted Fetuses |
| title_fullStr | Dimming the Powerhouse: Mitochondrial Dysfunction in the Liver and Skeletal Muscle of Intrauterine Growth Restricted Fetuses |
| title_full_unstemmed | Dimming the Powerhouse: Mitochondrial Dysfunction in the Liver and Skeletal Muscle of Intrauterine Growth Restricted Fetuses |
| title_short | Dimming the Powerhouse: Mitochondrial Dysfunction in the Liver and Skeletal Muscle of Intrauterine Growth Restricted Fetuses |
| title_sort | dimming the powerhouse mitochondrial dysfunction in the liver and skeletal muscle of intrauterine growth restricted fetuses |
| topic | mitochondrial metabolism tricarboxylic acid (TCA) cycle intrauterine growth restriction (IUGR) placental insufficiency oxidative phosphorylation |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2021.612888/full |
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