310. Award Talk: Immunometabolism Reprioritizes the Hierarchy of Nutrient Parturition During Growth.

Abstract Various stressors impair growth in livestock, with heat stress (HS) being among the most extensively researched due to its detrimental effects on all aspects of animal performance. Beyond reductions in feed intake, HS independently disrupts numerous endocrine, physiological, metabolic, circulatory, and immune parameters. These alterations are interconnected over time, centering on impaired integrity of the gastrointestinal tract (GIT) barrier. Increased GIT permeability permits leakage of luminal antigens into circulation, triggering immune activation with both localized and widespread inflammation. Upon stimulation, activated leukocytes predominantly shift to aerobic glycolysis from oxidative phosphorylation, demanding over 1 mg glucose per kg of metabolic body weight. Systemic adaptations prioritize glucose supply to immune cells, featuring elevated basal and post-stimulation insulin levels, increased cortisol and prolactin in circulation, and enhanced liver glucose production. This endocrine pattern coincides with reduced adipose tissue breakdown and insulin resistance in skeletal muscle. Notably, this physiological response closely mirrors that observed under diverse abiotic and biotic challenges, such as restricted feeding, weaning, cold exposure, auditory stress, and direct pathogen challenge, all sharing comparable metabolic and hormonal signatures. Fundamentally, these stressors can be viewed as “psychological” in nature, originating their detrimental effects from GIT barrier dysfunction. Such psychological stress impairs gastrointestinal epithelial function through at least two pathways: (1) degranulation of mast cells and (2) generation of a pro-oxidant milieu at the apical surface by immune cells, which counterintuitively promotes pathogen survival. Although stress is frequently described as immunosuppressive—explaining heightened disease susceptibility under adverse conditions—it remains uncertain if in vitro immune assays truly indicate suppression or instead capture the altered leukocyte behavior in vivo during ongoing immune activation driven by leaky gut.