The mechanistic action and application of a beta-3 selective adrenergic modulator (LY488756) in finishing cattle

Bohrer, Benjamin M

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https://hdl.handle.net/2142/109545 Copy

Description

Title

The mechanistic action and application of a beta-3 selective adrenergic modulator (LY488756) in finishing cattle

Author(s)

Bohrer, Benjamin M

Issue Date

2016-08-26

Director of Research (if dissertation) or Advisor (if thesis)

Boler, Dustin D

Doctoral Committee Chair(s)

Boler, Dustin D

Committee Member(s)

• Dilger, Anna C
• McKeith, Floyd K
• Loerch, Steven C
• Shipley, Clifford F

Department of Study

Animal Sciences

Discipline

Animal Sciences

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• cattle
• LY488756
• lubabegron fumerate
• ractopamine hydrochloride
• cattle metabolism
• adrenergic

Abstract

Animal-derived food products provide protein, vitamins, and minerals necessary for a healthy diet. In the next few decades, the expansion of global animal agriculture will be forced to keep pace with an expected world population growth of 2.3 billion people. Feeding the growing world will either mean producing more food with the same resources or making drastic changes to the way the world currently produces food. Growth promoting technology can be used in livestock production to increase live efficiency and improve yields of animal-derived food products. An example of a growth promoting technology in beef cattle is beta-adrenergic agonists. Research was conducted to gain a greater understanding of the mechanistic action and practical application of LY488756, a selective β3-adrenergic modulator, when fed to finishing cattle. When our efforts began, LY488756 was an investigational compound designed for the finishing phase of beef cattle. LY488756 is described as a selective β-adrenergic modulator with reported agonist effects on β3 adrenergic receptors and antagonistic effects on β1 and β2 adrenergic receptors. Much is still unknown about this compound, however clinical research suggests increased growth rate, improved feed efficiency, and more effective nutrient partitioning in finishing cattle. Using existing knowledge of beta-adrenergic agonist compounds (ractopamine hydrochloride, zilpaterol hydrochloride, and clenbuterol hydrochloride) may be helpful in understanding the basic mechanistic function and potential for application of LY488756. During the summer of 2014 (June-August), thirty-five finishing cattle were fed at the University of Illinois Beef and Sheep Field Research Laboratory. Cattle were fed LY488756 for 28 d or 56 d, ractopamine hydrochloride for 28 d or 56 d, or a control diet for 56 d. Primary objectives of this study were to study the effects of LY488756 on mechanistic action, which included beta-receptor subtype parameters, protein abundance of uncoupling protein-1, which is a marker of increased thermogenesis, and blood metabolic response. Protein expression was not different among treatments for any of the three β-adrenergic receptor subtypes when analyzed with western blotting procedures. Abundance of uncoupling protein-1 was not significantly increased in cattle fed LY488756 when compared with cattle not fed LY488756. Baseline and glucose-induced insulin levels were reduced in cattle fed LY488756 and in cattle fed ractopamine hydrochloride compared with cattle fed control. These results suggested 1) beta-receptor subtype proteins, although they may or may not remain active, were equally expressed after feeding cattle LY488756 for 28 d and 56 d, ractopamine hydrochloride for 28 d and 56 d, or a control diet; 2) cattle fed LY488756 did not experience increased thermogenesis as indicated by the lack of an increase in uncoupling protein-1; and 3) finishing cattle fed LY488756 and ractopamine hydrochloride become more insulin sensitive compared with cattle not fed LY488756 or ractopamine hydrochloride.

Graduation Semester

2016-12

Type of Resource

Thesis

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Copyright 2016 Benjamin M. Bohrer

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