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
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
Affiliations
Rachel L. Gibbs
Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USA
James A. Wilson
Department of Biology, University of Nebraska-Omaha, Omaha, NE 68182, USA
Rebecca M. Swanson
Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USA
Joslyn K. Beard
Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USA
Zena M. Hicks
Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USA
Haley N. Beer
Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USA
Eileen S. Marks-Nelson
Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USA
Ty B. Schmidt
Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USA
Jessica L. Petersen
Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USA
Dustin T. Yates
Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USA
Stress-induced fetal programming diminishes β2 adrenergic tone, which coincides with intrauterine growth restriction (IUGR) 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 (p p p p p p < 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.
