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Factors Regulating Muscle Protein Synthesis and Accretion in Horses
K. L. Urschel
Department of Animal and Food Sciences
Although the horse is widely recognized as an athletic animal, to date there has been little research in horses that has focused on the factors, such as exercise, age, feeding and diet composition, and the mechanisms that regulate muscle protein synthesis.
In humans, aging is associated with a loss of muscle mass known as sarcopenia and a similar decrease in lean mass with age has also been described in horses. In an athletic animal, an additional implication of the loss of muscle reduced is performance and an increased susceptibility to injury. One proposed cause of sarcopenia in humans is that there is a reduction in the rate of protein synthesis relative to the rate of protein breakdown, possibly due to dysfunctions in the mammalian target of rapamycin (mTOR) signaling pathway. There is limited data relating to the regulation of rates of whole-body and muscle protein synthesis and mTOR-related signaling in horses of any age and therefore additional research is necessary.
For a more complete understanding of the mechanisms underlying the loss of muscle mass in old horses, it is necessary to understand the factors regulating whole-body and muscle protein synthesis and metabolism in growing and mature healthy horses. This can be accomplished by studying the effects of various anabolic stimuli (ie. feeding, insulin) and physiological states (ie. growth, aging, exercise) on the activation of the translation initiation factors of the mTOR signaling pathway and on muscle and whole-body protein synthesis rates. Understanding the factors that regulate protein metabolism in old horses will allow for better management strategies to promote the maintenance of lean mass in this population of horses.
This research will elucidate the factors that regulate protein synthesis in horses of a variety of ages and physiological states and will help bring our level of understanding of protein synthesis in horses up to a level more comparable to other more intensely studied species such as rodents, pigs and humans. Once the factors underlying the regulation of protein synthesis are known, future studies can investigate ways to manipulate protein synthesis during critical times, including athletic training, old age and in disease states in order to encourage the accretion and maintenance of lean body mass.
The work to be conducted in growing horses (at rest and during exercise) may also be relevant to human adolescents, an age group where there is an absence of data relating to regulation of muscle protein synthesis. Furthermore, if the horse does in fact display similar age-related changes in protein synthesis as elderly humans, the horse may prove to be a useful research model for studying aspects of age-related sarcopenia that are not optimally studied using a rodent model.
2009 Project Description
This Hatch project is only in its very beginning phases. To date, the sample collection periods for Study 1 (Developing sampling methods and protocols to study the mTOR-related signaling in equine skeletal muscle)and Study 2 (Differences in mTOR-related signaling in skeletal muscle in yearling, 2 year old and mature horses have been completed). HPLC analysis of all plasma samples and feed samples from both studies has been completed, although statistical analyses have not been completed. The antibodies to be used in the Western blot analyses have been re-validated for use in equine muscle samples using blocking peptides. To date, we have completed the Western blot analysis of the Akt protein (both total and phosphorylated forms) in Study 2.
Other activities associated with this study include teaching and mentoring: this study is the PhD research of Ashley Wagner and it was her first time conducting research in horses. Over the course of these studies she learned catheterization and muscle biopsying techniques and she is continuing to learn and develop her laboratory techniques under my guidance. Additionally, other graduate and undergraduate students assisted with these projects and were exposed to the different techniques used.
So far, the only portion of this research that has been disseminated is the Akt data from Study 2 which was presented in poster form at the University of Kentucky Center for Muscle Biology annual retreat day.
At this time there are insufficient data/results available to comment on the outcomes or the impact of the research.
Abstracts: Wagner AL* and Urschel KL. Feeding, but not age, affects Akt phosphorylation in adolescent and mature horses. University of Kentucky Center for Muscle Biology 2009 Fall Retreat, Lexington KY, October 28, 2009. Abstract #17.
Submitted abstracts: Wagner AL*, Gould JC, Ennis RB and Urschel KL. The increase in Akt phosphorylation following feeding is independent of age in growing and mature Thoroughbred mares. Submitted for the 2010 Experimental Biology conference on November 3, 2009 (Submission #3089).