418 Awardee Talk: Heat Stress-Mediated Muscle Dysfunction

Abstract

Abstract Ongoing climate change with more frequent, longer-lasting, extreme heat events, threatens advances in efficient production and costs the U.S. Swine Industry more than $900 million annually. Continued selection for rapid lean tissue accretion may further compromise heat resistance as it is associated with greater metabolic heat production. The long-term objective of our work is to develop therapeutic strategies to mitigate the deleterious consequences of prolonged, environment-induced heat stress (HS) with a driving philosophy that elucidation of cellular and systemic pathologies caused by prolonged hyperthermia is a prerequisite to development of etiological interventions. Our working model suggests that in skeletal and cardiac muscle, HS causes Ca2+ dysregulation and subsequent mitochondrial dysfunction, which results in free radical injury and metabolic dysregulation. Oxidative stress may impair autophagy, the very process intended to remove damaged mitochondria, and contribute to an accumulation of damaged mitochondria. Our most recent data indicate that during HS, barrows were able to maintain growth despite a higher rectal temperature than gilts. Further, among other changes, HS caused mitochondrial hyper-fusion in gilts and dysregulation of the muscle metabolome was greater in gilts than barrows. Additionally, we discovered HS caused sex-specific reductions in mitochondrial function. These changes were associated with decreased degradation of autophagosomes and markers of mitophagy in muscle from gilts, but not barrows. Finally, muscle from barrows appeared resistant to oxidative stress, whereas in muscle from gilts, HS increased oxidative modification of lipids and nucleic acids. In an independent experiment, we considered HS-mediated consequences in the myocardium and discovered that 1 day of HS caused ventricle-specific architectural and biochemical changes in gilts. Our future work will focus on continued testing of our working model and consideration of recovery from HS as well as development of effective management and therapeutic strategies that can be economically deployed to offset HS-mediated losses.