Feeding beta adrenergic agonists alters mitochondria metabolism in porcine skeletal muscle.

During skeletal muscle growth, metabolic processes regulating muscle tissue exhibit remarkable adaptability. The objective of this study was to determine the involvement of mitochondria function in the shift of metabolism in porcine skeletal muscle. To alter metabolism, we utilized β-adrenergic agonists (BAA) supplementation known to increase the proportion of fast-twitch fibers. To assess the role of the mitochondria in this process, we utilized a naturally occurring mutation in domestic pigs containing a constitutively active adenosine monophosphate activated protein kinase (AMPKγ3R200Q) that results in greater tissue oxidative capacity. Mature pigs with or without AMPK mutation (control and AMPKγ3R200Q) were fed BAA (0 and 9 ppm) for 1 wk, then were euthanized and longissimus lumborum muscle samples were collected and mitochondria were isolated. Mitochondria from muscle of AMPKγ3R200Q pigs had higher (P < 0.05) oxygen consumption rates (OCR) than that of control pigs when using pyruvate/malate substrates under ADP-stimulated conditions. When provided succinate/rotenone substrates, an interaction (P < 0.05) was noted for basal respiration, where mitochondria from muscle of control pigs fed 0 ppm BAA had lower OCR compared to that of AMPKγ3R200Q pigs and that of those fed 9 ppm BAA. These data show that BAA have more pronounced effects on control pigs than AMPKγ3R200Q pigs which may be due to the inherently greater oxidative capacity of mutant pig muscle. After 1 wk of feeding BAA, there was an increase in β1-adrenergic receptor gene expression in pigs fed BAA (Treatment, P = 0.06; Interaction P = 0.08). Oxidative protein abundance increased for succinate dehydrogenase (P < 0.01) and citrate synthase (CS, P < 0.001) in AMPKγ3R200Q muscle. Additionally, CS activity in isolated mitochondria from muscle of AMPKγ3R200Q pigs was lower (P = 0.08), but whole muscle of AMPKγ3R200Q pigs had overall higher CS activity (P < 0.01). There were no differences in glycolytic enzyme protein abundances, however, there was increased lactate dehydrogenase (P < 0.001) activity in muscle of control pigs and that of muscle from pigs fed BAA (P < 0.05). Together, these data indicate that mitochondria function is altered in porcine skeletal muscle when pigs are supplemented with BAA and suggest part of the mechanism by which BAA supplementation augments muscle growth in pigs potentially lies within the regulation of β1-adrenergic receptors and changes in mitochondrial function.