140 Young Scholar Presentation: Immune activation and its effects on energetics and calcium homeostasis
Abstract Nutrient partitioning towards productive processes (i.e., milk production, growth, and reproduction) is key to economically profitable agriculture. During immune activation, the hierarchy of coordinated nutrient trafficking is reprioritized towards the immune system at the expense of production. Dairy cows encounter frequent immune challenges, as bacterial insults can originate from a myriad of sources including the uterus, mammary gland, and gastrointestinal tract. Regardless of the origin, immune activation hinders animal welfare and evidence suggests it may play a role in many post-calving undesirable phenotypes (i.e., decreased DMI, increased NEFA, hypocalcemia). Following activation, leukocytes undergo a metabolic shift from oxidative phosphorylation to aerobic glycolysis (a phenomenon known as the “Warburg effect”) and begin consuming copious amounts of glucose. In a lactating cow the glucose requirement of the acutely activated immune system exceeds 1 kg in a 12-hour period. To ensure adequate glucose delivery to leukocytes several well-characterized metabolic adjustments are employed including hyperglycemia or hypoglycemia (depending on the stage and severity of infection), increased insulin and glucagon, increased skeletal muscle catabolism, hypertriglyceridemia, and hypoketonemia. The energetic burden of immune activation is intensified by a simultaneous decrease in feed intake and thus reduced intestinally derived substrates. In addition to energetic metabolism, immune activation induces a marked and sustained decrease in circulating calcium (Ca). Recently, we have demonstrated that the total Ca deficit was ~20 g during an acute (12 hour) and intense model of immune activation. Infection-induced hypocalcemia is a species conserved response, yet, it remains largely unknown what role Ca plays during infection and why it acutely decreases. Although, evidence suggests it may serve as a protective strategy to prevent a hyper-inflammatory systemic response during infection. In summary, immune activation negatively influences metabolic, hormonal, and Ca homeostasis and these alterations closely mimic changes observed in poorly transitioning dairy cows. Having a better understanding of the impact of immune activation on nutrient trafficking and Ca homeostasis will provide foundational information for developing strategies aimed at minimizing production losses during infection.