Research Accomplishment Reports 2010

Factors Regulating Muscle Protein Synthesis and Accretion in Horses

K. L. Urschel
Department of Animal and Food Sciences

 

Non-Technical Summary

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.

2010 Project Description

This year, the majority of the sample analysis for the "Developing sampling methods and protocols to study the mTOR-related signaling in equine skeletal muscle" and the "Differences in mTOR-related signaling in skeletal muscle in yearling, 2 year old and mature horses" projects was completed. Specifically, the Western immunoblot analysis for the mTOR-related signaling factors, plasma insulin and glucose concentrations, plasma, tissue and feed amino acid concentrations were determined in both studies.

Additionally, the animal sampling portions of the study entitled "Quantifying differences in muscle protein synthesis between mature and "old" horses" was completed and sample analysis is underway, with the majority of the Western immunoblot analysis already completed. This study was slightly different than the originally proposed study, with the omission of the euglycemic, isoaminoacidemic insulin clamp procedures, because it was performed in conjunction with a related study that was funded by an outside organization (Morris Animal Foundation).

At this time, the outputs have been disseminated primarily in abstract form and as presentations at scientific meetings. In the last year, abstracts were submitted to Experimental Biology 2010 (1 abstract, presented as a poster), ASAS annual meeting 2010 (1 abstract, presented as a 15 minute talk), at the University of Kentucky Center for Muscle Biology Annual Retreat (2 abstracts, presented as posters), and at the Dorothy Havemeyer Equine Geriatric Workshop (1 abstract, presented as a 30 minute talk). Additionally, 1 abstract has been submitted to Experimental Biology 2011.

2010 Impact

This project is still in its relatively early stages and final results are still somewhat limited. At this time, we have been able to show that the depth at which muscle biopsy samples are obtained does not appear to affect mTOR-related signaling in response to feeding. This information will be useful in the design and interpretation of future studies.

Additionally, in the completed study that compared the effects of age (yearling versus two year old versus mature) on the responsiveness of mTOR-related signaling to feeding, there does not appear to be a consistent age effect: all ages of horses studied appeared to have muscle that was equally responsive to feeding in terms of the activation of muscle protein synthesis. Based on research in other species, we had expected the younger horses to be more responsive than the older horses; however, it is possible that we did not study young enough (ie. less than 1 year) horses and therefore missed the critical time point where there were age-related changes. This study will need to be repeated using younger horses to quantify the changes in the activation of muscle protein synthesis that occur in the first year of life.

Quantifying the factors that regulate muscle protein synthesis during growth and maturity could have important implications in how horses are fed (amounts and timing of protein feeding) and managed, in order to optimize muscle protein accretion; although additional research is certainly needed. Results are not yet available for the "old horse" study; however, it is expected that there will be differences in muscle protein metabolism in "old" horses, and these changes will partially explain the loss of muscle mass that occurs during the aging process. In the future this will help us to develop strategies to help old horses maintain muscle mass and quality of life.

2010 Publications

Tanner SL, Wagner AL and Urschel KL. Biopsy depth had no effect on amino acid concentrations or translation initiation factor activation in equine gluteus medius muscle. University of Kentucky Center for Muscle Biology 2010 Fall Retreat, Lexington KY, October 28, 2010. Abstract 7. Poster presentation given by S.L. Tanner.

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. Experimental Biology 2010, Anaheim CA, April 24 to 28, 2010. FASEB J 24: Abstract 927.7. Poster presentation by A.L. Wagner

Wagner AL, Gould JC, Ennis RB and Urschel KL. Ontogenic changes in the activation of translation initiation factors post feeding are not seen in adolescent Thoroughbred mares. 2010 Joint ADSA-PSA-AMPA-CSAS-ASAS Meeting July 11 to 15, 2010. J Anim Sci 88 (E-Suppl 2) (J Dairy Sci 93 (E-Suppl 1)): Abstract 109. Oral presentation by A.L. Wagner.

Urschel KL, Wagner AL and Horohov DW. Effects of old age on protein metabolism in horses. 2010 Dorothy Havemeyer Geriatric Workshop October 24 to 27, 2010. p.5. An invited presentation was given at the workshop by K.L. Urschel.

Wagner AL, Ennis RB, Horohov DW and Urschel KL Administration of phenylbutazone to mature and geriatric horses influences the activation of factors in the mTOR signaling pathway. University of Kentucky Center for Muscle Biology 2010 Fall Retreat, Lexington KY, October 28, 2010. Abstract 8. Poster presentation given by A.L. Wagner