Beta adrenergic agonist induces a shift in mitochondria metabolism in porcine skeletal muscle

During phases of skeletal muscle growth, the metabolic processes regulating muscle tissue exhibit remarkable adaptability. This metabolic flexibility is an essential component of maintaining the health and functionality of skeletal muscle, which allows the capacity to transition between oxidative and glycolytic metabolic pathways. Within the occurrence of these metabolic shifts, the exact underlying mechanisms that orchestrate these transitions within the context of mitochondrial function remain unresolved. Therefore, our objective is to determine the role of mitochondria during a shift in metabolism, through measuring functional capacity, gene expression, and protein abundance. To investigate this shift, we utilized β-adrenergic agonists (BAA) supplementation, due to its ability to increase the proportion of fast-twitch fibers in skeletal muscle. To assess the role of the mitochondria, we utilized a mutated pig, containing a constitutively active adenosine monophosphate activated protein kinase (AMPKγ3R200Q) that contains a greater oxidative capacity in a habitually glycolytic skeletal muscle. In this current study, mature pigs (wildtype and AMPKγ3R200Q) were fed BAA (0 and 9ppm) for 1 week, then euthanized and longissimus dorsi muscle samples were collected. Mitochondria of AMPK mutated pigs had a higher ( P = 0.08) oxygen consumption rate with pyruvate/malate substrates when stimulated with ADP when compared to their wildtype (WT) counterpart. When given succinate/rotenone substrates, there was an interaction ( P = 0.04) noted for basal respiration, where WT pigs fed control diets had lower oxygen consumption compared to that of AMPK mutated pigs and those fed BAA. These data suggest that BAA has more of an effect on WT pigs than AMPK mutated pigs, possibly due to the inherent increased oxidative metabolism in mutant pigs. In addition, skeletal muscle mitochondria of AMPK mutated pigs had higher ( P = 0.04) maximal respiration compared to that of their WT counterpart. After 1 week of feeding BAA, there were no differences in mitochondrial DNA content, but there was an increase in β1-adrenergic receptor gene expression in pigs fed BAA (Diet, P = 0.06; Interaction P = 0.08). Oxidative protein abundance increased for succinate dehydrogenase ( P < 0.01) and citrate synthase ( P = 0.08) in the skeletal muscle of AMPK mutated pigs. Glycolytic proteins were increased for lactate dehydrogenase ( P < 0.05) and glyceraldehyde 3-phosphate dehydrogenase ( P < 0.01) in the muscle of WT pigs. No interactions between genotype and diet on the protein abundance level was noted. Together, these data show that mitochondria function is altered in porcine skeletal muscle when pigs are supplemented with 1 week of BAA; however, it is not detected in protein levels after 1 week. These data suggest part of the mechanism by which BAA supplementation augments muscle growth in pigs lies within the regulation of β1-adrenergic receptors and changes in mitochondrial function. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.