Effects of weaning age and pace on blood metabolites, cortisol concentration, and mRNA abundance of inflammation-related genes in gastrointestinal, adipose, and liver tissue of Holstein dairy calves.

The objective of this study was to evaluate the effects of weaning age and pace on blood metabolites, cortisol concentration, and mRNA abundance of inflammation-related genes in Holstein dairy calves. A total of 70 1-d-old calves (38.8 ± 4.4 kg BW ± SD), blocked by sex and birth BW, were randomly assigned to a 2 × 2 factorial arrangement of treatments. The first factor was weaning age, which was either early (6 wk) or late (8 wk). The second factor was weaning pace, which was either abrupt (4 steps down over 3 d; the initial milk replacer was 7.6 L, which was reduced by 1.9 L in each step-down) or gradual (7 steps down over 14 d; the initial milk replacer was 7.6 L, which was reduced by 1.09 L in each step-down), generating early-abrupt (EA), early-gradual (EG), late-abrupt (LA), and late-gradual (LG) treatments. All treatments had 10 female and 8 male calves, except EA that had 1 fewer male calf. Milk replacer (24% CP, 17% fat) was bottle fed, up to 1,200 g/d, twice daily (0600 h and 1800 h). The EA and EG treatment calves received 46.2 kg of milk replacer, and the LA and LG treatment calves received 63 kg of milk replacer. The study had 2 cohorts (2020, n = 40; 2021, n = 31), and each cohort included all treatments. Blood was collected from the jugular vein at 0900 h at 3 and 7 d of age, and a day before starting and a day after weaning completion. Male calves were humanely killed a day after weaning. Rumen, jejunum, large intestine, liver, omental adipose and perirenal adipose tissues were sampled to determine the mRNA abundance of inflammation-related genes. Weaning pace, age, pace × age, birth BW, and sex were included as fixed and cohort was included as random effects in the model. Blood metabolites and cortisol were analyzed as repeated measures, and sampling day, pace × sampling day, and age × sampling day were also included as additional fixed effects. Significance was noted at P ≤ 0.05 and tendencies when 0.05 <P ≤ 0.10. The EA calves showed a tendency to have the greatest nonesterified fatty acid (NEFA) concentration compared with all other treatments. We observed a pace × day effect on serum NEFA and BHB; calves weaned at an abrupt pace had an increased level of NEFA after weaning compared with those weaned gradually. Calves weaned at the gradual pace showed the greatest serum BHB after weaning. Most mRNA abundances for inflammation-related genes affected by treatments showed a similar pattern. They were downregulated by the abrupt (liver IL-1β) and early weaning (jejunum TNF-α and ICAM), and in some cases, the interaction intensified the effect, demonstrating a weakened immune response in calves experiencing more stressful conditions (EA: IL-6 in the liver and NF-κB in the perirenal adipose tissue). Overall, the downregulation of the mRNA abundance of inflammation-related genes in EA calves may be attributed to the suppression of the immune system and an immature immune response. Furthermore, the greater NEFA in EA calves could be attributed to a reduced starter intake, less developed rumen, or shorter time during the weaning transition.