Principal Investigator: Stephanie Valberg, Ph.D.
Although the proximal cause of Duchenne Muscular Dystrophy (DMD) is the loss of the sarcolemmal protein, dystrophin, this leads to muscular degeneration because of a series of cascading effects, including loss of structural integrity in the muscle, and energy failure that undercuts muscle function. The energy component of DMD is exemplified by the fact that creatine has a beneficial effect on many boys with DMD, although this compound does not directly increase energy production in muscle but does help store energy and improve stamina. During daily exercise, glycogen (sugar stored in the liver and muscle) and fatty acids derived from fat stores, are burned to provide energy. Boys with DMD have continual leakage of metabolic intermediates through disrupted muscle cell membranes, leading to inadequate cellular energy metabolism. Thus some of the weakness in these boys is due to metabolic exhaustion. Dietary therapies for children with metabolic myopathies and muscular dystrophy usually involve the addition of fats containing an even number of carbon atoms, which are often poorly metabolized. We propose to develop a new nutritional treatment for children with metabolic myopathies or muscular dystrophies by using a synthetic fat [triheptanoin (containing 7 carbon atoms), which is metabolized into a three carbon compound and a two carbon compound. The three carbon compound is unique in that it is used instead of glycogen to replenish metabolic intermediate compounds, which helps maintain the cell’s ability to burn fats, and thus greatly increases muscle energy production. To determine the muscles ability to use C7, and to carefully monitor its effect on muscle function, we propose to study its effectiveness in treating an experimental model of muscle disease in horses. These athletic animals serve as excellent models due to their similar muscle fiber composition to humans and their high metabolic rate. Horses will perform 90 min of submaximal exercise on 2 fat diets, C7 and corn oil (C18). Our specific aims are to contrast C7 and C18 (even carbon length) diets to determine: (1) differences in blood and urine fat metabolites and fat utilization during exercise; (2) if C7 replenishes metabolic intermediates better than C18; (3) if of muscle energy depletion during submaximal exercise is less with C7 than C18. Our verification of an effective means of increasing muscle energy production will provide us with a novel way to improve energy production in DMD, which would slow muscle degeneration in that disease.