Studies on Exercise and Glycogen Re- synthesis in Skeletal Muscles of Pigs with the PRKAG3 Mutation

AMP-activated protein kinase (AMPK) plays an important role in the regulation of glucose and lipid metabolism in skeletal muscle. Many pigs of Hampshire origin have a naturally occurring mutation situated in the PRKAG3 gene which encodes a muscle-specific isoform of the AMPK γ3-subunit. This mutation results in excessive glycogen storage mainly in white glycolytic skeletal muscle and an increased muscle oxidative capacity. This thesis examined the in vivo effect of the PRKAG3 mutation on skeletal muscles in association with exercise. The pigs performed standardised treadmill exercise tests before and after a 5-week training period. Muscle samples (m. biceps femoris) and blood samples were taken before and after exercise and in the recovery phase. Muscle samples from m. masseter, m. biceps femoris, m. semitendinosus and m. longissimus dorsi were taken after euthanasia. Glycogen content and its two fractions (proglycogen and macroglycogen), enzyme activity, fibre type characteristics and expression/phosphorylation of signalling proteins were analysed. Insulin, glucose, lactate and free fatty acid concentrations were analysed on the blood samples. Compared with non-carriers, carriers of the PRKAG3 mutation had higher macroglycogen content in skeletal muscles. At 3 h but not 6 h of recovery following exercise, re-synthesis of glycogen, especially of macroglycogen was higher in carriers than in non-carriers. The metabolic blood response did not differ between the genotypes. Expression of AMPK in muscle was lower in carriers than in non-carriers. The increased rate of glycogen synthesis following exercise in carriers was correlated with an increased signalling response of Akt and its substrate AS160 and a higher activity of hexokinase. This indicated increased glucose influx and phosphorylation of glucose, directed towards glycogen synthesis. The carriers had a lower percentage and relative area of type IIB fibres in m. biceps femoris and m. longissimus dorsi than non-carriers. In m. longissimus dorsi, carriers had a higher percentage of type IIAX fibres and higher citrate synthase activity. In conclusion, the PRKAG3 mutation influences, mainly the macroglycogen fraction and muscle characteristics in exercise-trained pigs, promoting varying degrees of oxidative phenotype in muscles with different functions.