The Role of Postnatal Adrenergic Manipulation in the Mediation of Fetal Programming Adaptions in Growth and Skeletal Muscle Glucose Metabolism That Persist in the Juvenile IUGR-born Lamb

Authors

Rachel L. Gibbs, University of Nebraska - LincolnFollow

First Advisor

Dr. Dustin Yates

Date of this Version

Summer 7-2020

Comments

A THESIS Presented to the Faculty of The Graduate College at the University of Nebraska In Partial Fulfillment of Requirements For the Degree of Master of Science, Major: Animal Science, Under Supervision of Professor Dustin T. Yates. Lincoln, Nebraska: July 2020

Copyright 2020 Rachel L. Gibbs

Abstract

Our 1^st study assessed growth deficits in IUGR juvenile lambs and the benefits of treatment with adrenergic and inflammatory mediators. Growth metrics including bodyweight, rate of gain, and crown-rump length were diminished by placental insufficiency-induced IUGR through 2 mo. of age but were recovered by daily clenbuterol or curcumin supplementation. Body composition metrics indicated by bioelectrical impedance, proximate analysis, and loin size revealed that fat-free lean mass, specific muscle group sizes, and protein-to-fat ratios were reduced in unsupplemented IUGR lambs but recovered to or even past controls in clenbuterol-supplemented lambs. From these findings, we conclude that IUGR impairs postnatal growth and body composition through the juvenile stage, but postnatal treatment with clenbuterol or curcumin effectively recovered some aspects of diminished growth and improved body composition in IUGR lambs.

Our 2^nd study determined whether IUGR-induced fetal programming previously observed in skeletal muscle glucose metabolism and pancreatic β cell function progressed in juvenile-aged offspring and whether postnatal adrenergic modification via daily clenbuterol injection improves these deficits. Juvenile IUGR lambs continued to exhibit reduced skeletal muscle glucose oxidation and glucose-stimulated insulin secretion (GSIS). Clenbuterol effects on glucose metabolism in IUGR muscle varied. In vivo hindlimb glucose uptake and oxidation were improved by clenbuterol, but ex vivo glucose uptake was not improved and ex vivo glucose oxidation was further reduced in clenbuterol-supplemented IUGR primary muscle. Clenbuterol also recovered GSIS in IUGR lambs. Thus, results suggest that IUGR adaptions in insulin-stimulated glucose metabolism progress through the juvenile age. Furthermore, clenbuterol supplementation is effective when administered daily but loses its effect when removed.

Our 3^rd study sought to determine the impact of stress on BIA-estimated body composition in neonatal IUGR-born lambs and in heat-stressed feedlot wethers. The BIA successfully detected changes in fat-free mass and fat-free soft tissue in IUGR neonatal lamb at 25 d of age and in heat-stressed wethers but not in IUGR lambs at 3 d of age. The BIA, however did not detect differences in nutrient or specific muscle group mass in either cohort. Thus, we conclude that BIA reasonably estimates stress-induced changes in lamb body composition, except in very young animals.

Advisor: Dustin T. Yates