Daily Injection of the β2 Adrenergic Agonist Clenbuterol Improved Muscle Glucose Metabolism, Glucose-Stimulated Insulin Secretion, and Hyperlipidemia in Juvenile Lambs Following Heat-Stress-Induced Intrauterine Growth Restriction
Stress-induced fetal programming diminishes β2 adrenergic tone, which coincides with intrauterine growth restriction (<b>IUGR</b>) and lifelong metabolic dysfunction. We determined if stimulating β2 adrenergic activity in IUGR-born lambs would improve metabolic outcomes. IUGR lambs that...
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MDPI AG
2024-03-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/14/3/156 |
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| author | Rachel L. Gibbs James A. Wilson Rebecca M. Swanson Joslyn K. Beard Zena M. Hicks Haley N. Beer Eileen S. Marks-Nelson Ty B. Schmidt Jessica L. Petersen Dustin T. Yates |
| author_facet | Rachel L. Gibbs James A. Wilson Rebecca M. Swanson Joslyn K. Beard Zena M. Hicks Haley N. Beer Eileen S. Marks-Nelson Ty B. Schmidt Jessica L. Petersen Dustin T. Yates |
| author_sort | Rachel L. Gibbs |
| collection | DOAJ |
| description | Stress-induced fetal programming diminishes β2 adrenergic tone, which coincides with intrauterine growth restriction (<b>IUGR</b>) and lifelong metabolic dysfunction. We determined if stimulating β2 adrenergic activity in IUGR-born lambs would improve metabolic outcomes. IUGR lambs that received daily injections of saline or the β2 agonist clenbuterol from birth to 60 days were compared with controls from pair-fed thermoneutral pregnancies. As juveniles, IUGR lambs exhibited systemic inflammation and robust metabolic dysfunction, including greater (<i>p</i> < 0.05) circulating TNFα, IL-6, and non-esterified fatty acids, increased (<i>p</i> < 0.05) intramuscular glycogen, reduced (<i>p</i> < 0.05) circulating IGF-1, hindlimb blood flow, glucose-stimulated insulin secretion, and muscle glucose oxidation. Daily clenbuterol fully recovered (<i>p</i> < 0.05) circulating TNFα, IL-6, and non-esterified fatty acids, hindlimb blood flow, muscle glucose oxidation, and intramuscular glycogen. Glucose-stimulated insulin secretion was partially recovered (<i>p</i> < 0.05) in clenbuterol-treated IUGR lambs, but circulating IGF-1 was not improved. Circulating triglycerides and HDL cholesterol were elevated (<i>p</i> < 0.05) in clenbuterol-treated IUGR lambs, despite being normal in untreated IUGR lambs. We conclude that deficient β2 adrenergic regulation is a primary mechanism for several components of metabolic dysfunction in IUGR-born offspring and thus represents a potential therapeutic target for improving metabolic outcomes. Moreover, benefits from the β2 agonist were likely complemented by its suppression of IUGR-associated inflammation. |
| first_indexed | 2024-04-24T18:01:37Z |
| format | Article |
| id | doaj.art-796faf6ba8084cc28e137e9b559de208 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-04-24T18:01:37Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-796faf6ba8084cc28e137e9b559de2082024-03-27T13:54:09ZengMDPI AGMetabolites2218-19892024-03-0114315610.3390/metabo14030156Daily Injection of the β2 Adrenergic Agonist Clenbuterol Improved Muscle Glucose Metabolism, Glucose-Stimulated Insulin Secretion, and Hyperlipidemia in Juvenile Lambs Following Heat-Stress-Induced Intrauterine Growth RestrictionRachel L. Gibbs0James A. Wilson1Rebecca M. Swanson2Joslyn K. Beard3Zena M. Hicks4Haley N. Beer5Eileen S. Marks-Nelson6Ty B. Schmidt7Jessica L. Petersen8Dustin T. Yates9Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USADepartment of Biology, University of Nebraska-Omaha, Omaha, NE 68182, USADepartment of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USADepartment of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USADepartment of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USADepartment of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USADepartment of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USADepartment of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USADepartment of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USADepartment of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USAStress-induced fetal programming diminishes β2 adrenergic tone, which coincides with intrauterine growth restriction (<b>IUGR</b>) and lifelong metabolic dysfunction. We determined if stimulating β2 adrenergic activity in IUGR-born lambs would improve metabolic outcomes. IUGR lambs that received daily injections of saline or the β2 agonist clenbuterol from birth to 60 days were compared with controls from pair-fed thermoneutral pregnancies. As juveniles, IUGR lambs exhibited systemic inflammation and robust metabolic dysfunction, including greater (<i>p</i> < 0.05) circulating TNFα, IL-6, and non-esterified fatty acids, increased (<i>p</i> < 0.05) intramuscular glycogen, reduced (<i>p</i> < 0.05) circulating IGF-1, hindlimb blood flow, glucose-stimulated insulin secretion, and muscle glucose oxidation. Daily clenbuterol fully recovered (<i>p</i> < 0.05) circulating TNFα, IL-6, and non-esterified fatty acids, hindlimb blood flow, muscle glucose oxidation, and intramuscular glycogen. Glucose-stimulated insulin secretion was partially recovered (<i>p</i> < 0.05) in clenbuterol-treated IUGR lambs, but circulating IGF-1 was not improved. Circulating triglycerides and HDL cholesterol were elevated (<i>p</i> < 0.05) in clenbuterol-treated IUGR lambs, despite being normal in untreated IUGR lambs. We conclude that deficient β2 adrenergic regulation is a primary mechanism for several components of metabolic dysfunction in IUGR-born offspring and thus represents a potential therapeutic target for improving metabolic outcomes. Moreover, benefits from the β2 agonist were likely complemented by its suppression of IUGR-associated inflammation.https://www.mdpi.com/2218-1989/14/3/156carbohydrate metabolismdevelopmental origins of health and diseaseDOHaDfetal programmingmetabolic dysfunction |
| spellingShingle | Rachel L. Gibbs James A. Wilson Rebecca M. Swanson Joslyn K. Beard Zena M. Hicks Haley N. Beer Eileen S. Marks-Nelson Ty B. Schmidt Jessica L. Petersen Dustin T. Yates Daily Injection of the β2 Adrenergic Agonist Clenbuterol Improved Muscle Glucose Metabolism, Glucose-Stimulated Insulin Secretion, and Hyperlipidemia in Juvenile Lambs Following Heat-Stress-Induced Intrauterine Growth Restriction Metabolites carbohydrate metabolism developmental origins of health and disease DOHaD fetal programming metabolic dysfunction |
| title | Daily Injection of the β2 Adrenergic Agonist Clenbuterol Improved Muscle Glucose Metabolism, Glucose-Stimulated Insulin Secretion, and Hyperlipidemia in Juvenile Lambs Following Heat-Stress-Induced Intrauterine Growth Restriction |
| title_full | Daily Injection of the β2 Adrenergic Agonist Clenbuterol Improved Muscle Glucose Metabolism, Glucose-Stimulated Insulin Secretion, and Hyperlipidemia in Juvenile Lambs Following Heat-Stress-Induced Intrauterine Growth Restriction |
| title_fullStr | Daily Injection of the β2 Adrenergic Agonist Clenbuterol Improved Muscle Glucose Metabolism, Glucose-Stimulated Insulin Secretion, and Hyperlipidemia in Juvenile Lambs Following Heat-Stress-Induced Intrauterine Growth Restriction |
| title_full_unstemmed | Daily Injection of the β2 Adrenergic Agonist Clenbuterol Improved Muscle Glucose Metabolism, Glucose-Stimulated Insulin Secretion, and Hyperlipidemia in Juvenile Lambs Following Heat-Stress-Induced Intrauterine Growth Restriction |
| title_short | Daily Injection of the β2 Adrenergic Agonist Clenbuterol Improved Muscle Glucose Metabolism, Glucose-Stimulated Insulin Secretion, and Hyperlipidemia in Juvenile Lambs Following Heat-Stress-Induced Intrauterine Growth Restriction |
| title_sort | daily injection of the β2 adrenergic agonist clenbuterol improved muscle glucose metabolism glucose stimulated insulin secretion and hyperlipidemia in juvenile lambs following heat stress induced intrauterine growth restriction |
| topic | carbohydrate metabolism developmental origins of health and disease DOHaD fetal programming metabolic dysfunction |
| url | https://www.mdpi.com/2218-1989/14/3/156 |
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