Whole-body phenylalanine kinetics and skeletal muscle protein signaling in horses with pituitary pars intermedia dysfunction

Laurel M. Mastro Departments of Animal and Food Sciences, College of Agriculture, Food and the Environment, University of Kentucky, Lexington, KY 40546.

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Amanda A. Adams Veterinary Science, College of Agriculture, Food and the Environment, University of Kentucky, Lexington, KY 40546.

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Kristine L. Urschel Departments of Animal and Food Sciences, College of Agriculture, Food and the Environment, University of Kentucky, Lexington, KY 40546.

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Abstract

Objective—To compare whole-body phenylalanine kinetics and the abundance of factors in signaling pathways associated with skeletal muscle protein synthesis and protein breakdown between horses with pituitary pars intermedia dysfunction (PPID) and age-matched control horses without PPID.

Animals—12 aged horses (6 horses with PPID and 6 control horses; mean age, 25.0 and 25.7 years, respectively).

Procedures—Plasma glucose, insulin, and amino acids concentrations were determined before and 90 minutes after feeding. Gluteal muscle biopsy samples were obtained from horses 90 minutes after feeding, and the abundance and activation of factors involved in signaling pathways of muscle protein synthesis and breakdown were determined. The next day, horses received a priming dose and 2 hours of a constant rate infusion of 13C sodium bicarbonate followed by a priming dose and 4 hours of a constant rate infusion of 1-13C phenylalanine IV; whole-body protein synthesis was determined.

Results—Plasma glucose and insulin concentrations were higher after feeding than they were before feeding for both groups of horses; however, no significant postprandial increase in plasma amino acids concentrations was detected for either group. Phenylalanine flux, oxidation, release from protein breakdown, and nonoxidative disposal were not significantly different between groups. No significant effect of PPID status was detected on the abundance or activation of positive or negative regulators of protein synthesis or positive regulators of protein breakdown.

Conclusions and Clinical Relevance—Results of this study suggested that whole-body phenylalanine kinetics and the postprandial activation of signaling pathways that regulate protein synthesis and breakdown in muscles were not affected by PPID status alone in aged horses.

Abstract

Objective—To compare whole-body phenylalanine kinetics and the abundance of factors in signaling pathways associated with skeletal muscle protein synthesis and protein breakdown between horses with pituitary pars intermedia dysfunction (PPID) and age-matched control horses without PPID.

Animals—12 aged horses (6 horses with PPID and 6 control horses; mean age, 25.0 and 25.7 years, respectively).

Procedures—Plasma glucose, insulin, and amino acids concentrations were determined before and 90 minutes after feeding. Gluteal muscle biopsy samples were obtained from horses 90 minutes after feeding, and the abundance and activation of factors involved in signaling pathways of muscle protein synthesis and breakdown were determined. The next day, horses received a priming dose and 2 hours of a constant rate infusion of 13C sodium bicarbonate followed by a priming dose and 4 hours of a constant rate infusion of 1-13C phenylalanine IV; whole-body protein synthesis was determined.

Results—Plasma glucose and insulin concentrations were higher after feeding than they were before feeding for both groups of horses; however, no significant postprandial increase in plasma amino acids concentrations was detected for either group. Phenylalanine flux, oxidation, release from protein breakdown, and nonoxidative disposal were not significantly different between groups. No significant effect of PPID status was detected on the abundance or activation of positive or negative regulators of protein synthesis or positive regulators of protein breakdown.

Conclusions and Clinical Relevance—Results of this study suggested that whole-body phenylalanine kinetics and the postprandial activation of signaling pathways that regulate protein synthesis and breakdown in muscles were not affected by PPID status alone in aged horses.

Contributor Notes

This manuscript represents a portion of a thesis submitted by Laurel Mastro to the University of Kentucky Department of Animal and Food Sciences as partial fulfillment of the requirements for a Master of Science degree.

Supported by the Morris Animal Foundation First Award Grant (D09EQ-310).

The authors thank Sara Tanner, Tammy Brewster-Barnes, and Nicole Holownia for assistance with care of the horses and sample collection. Dr. Macarena Sanz for placement of IV catheters in horses, and Dr. Jessica Suagee for assistance with statistical analysis.

The information reported in this manuscript is part of a project of the Kentucky Agricultural Experiment Station and is published with the approval of the director.

Address correspondence to Dr. Urschel (klur222@uky.edu).
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