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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.
2011 Project Description
1 student, Ashley Wagner, successfully defended her PhD thesis on November 21, 2011 that was based research that was a part of this project. In addition to Ashley, an additional PhD student, 1 technician and several other graduate and undergraduate students worked on this research. This year we primarily completed work that was already in progress.
We completed all sample analysis, statistical analysis and manuscript preparation for the studies related to Objectives 1 (Development of muscle biopsy techniques to measure mTOR signaling). Two manuscripts are in the final stages of preparation prior to submission. Additionally, this research is included as a part of a PhD thesis and some has also been presented at the American Society of Animal Science Annual Meeting (2011).
In relation to Objective 2, we completed the sample analysis and manuscript preparation for a study looking at the effects of post-natal age on mTOR signaling in growing horses. This manuscript was recently accepted for publication in the American Journal of Veterinary Research. This research was also included in a PhD thesis and was presented at scientific meetings in 2010.
The research, sample analysis and manuscript preparation has also been completed for studies related to Objective 3. Two manuscripts have been prepared: one comparing whole-body and muscle protein metabolism between mature and old horses and a second looking at the effects of anti-inflammatory administration on protein metabolism in old horses.
These papers will be submitted once other papers (the paper referred to above related to Objective 2 and another paper based on my post-doctoral research which has been accepted in the Journal of Nutrition) are in press. Results from this research have also been presented at Experimental Biology 2011 and the 2011 Equine Science Society meeting, and are included as a part of a PhD thesis.
Based on the results related to Objective 1, we have determined that sampling depth does not affect the measured mTOR signaling values. This will have important implications for studies that we will conduct in the future.
In the second study related to this objective, we found that mTOR signaling is not affected by repeated sample collection when the collection periods are separated by 24 hours and an anti-inflammatory is administered. However, if an anti-inflammatory is not administered, repeated sampling results in an increase in mTOR signaling, likely due to increased inflammation and tissue repair. This study also provides us with useful information for future study design.
For the research related to Objective 2, we found that mTOR signaling in the muscle of yearlings is more sensitive to feeding stimuli than mTOR signaling in 2 year olds. This is in agreement with findings in other species, which found that muscle protein synthesis (mTOR signaling) is most responsive to anabolic stimuli in young, growing animals. Conversely, we found that in "old" horses in a post-absorptive (quasi-fasted) state, there was reduced mTOR signaling compared to mature horses.
With regards to Objective 3, we found that "healthy" old horses did not have any differences in whole-body or muscle protein metabolism compared to the older mature horse. However, when the older horses were treated with an anti-inflammatory for 4 weeks, there were improvements in both whole-body and muscle protein synthesis and metabolism.
Overall, the results from this research project will allow for improved sample collection procedures and for the development of targeted feeding and management practices to promote the accretion and maintenance of muscle mass in horses of all ages.
Wagner AL and Urschel KL. Developmental regulation of the activation of translation initiation factors in response to feeding in the skeletal muscle of horses. Am J Vet Res, accepted August 18, 2011 (AJVR-11-06-0205).
Wagner AL, Ennis RB, Betancourt A, Adams AA, Horohov DW and Urschel KL. The effects of non-steroidal anti-inflammatory drug administration on systemic and muscle inflammation in mature and aged horses. Journal of Equine Veterinary Science, 31(5-6): 295-296. (From the 2011 Equine Science Society meeting)
Wagner AL, Ennis RB and Urschel KL. Non-steroidal anti-inflammatory drug administration and repeated muscle biopsies affect the phosphorylation of translation initiation factors. Submitted to the 2011 ADSA-ASAS Joint Annual Meeting, New Orleans LA, 07/10/2011 - 07/14/2011. J Anim Sci 88(E-suppl 2): Abstract 542.
Wagner AL, Ennis RB, Adams AA, Horohov DW and Urschel KL. Nonsteroidal anti-inflammatory drug administration to mature and old horses influences the activation of translation initiation factors. Experimental Biology 2011, Washington DC, 04/09/2011 - 04/13/2011. FASEB J 25: Abstract 109.7.