Accurately quantifying activated immune system energy requirements in vivo is difficult, but a better understanding may advance strategies to maximize animal productivity. Study objectives were to estimate whole-body glucose utilization following an i.v. endotoxin challenge. Lactating Holstein cows were jugular catheterized and assigned 1 of 3 bolus treatments: control (CON; 5 mL of saline; n = 6), lipopolysaccharide (LPS)-administered (LPS-C; 1.5 μg/kg of body weight; Escherichia coli 055:B5; n = 6), and LPS + euglycemic clamp (LPS-Eu; 1.5 μg/kg of body weight; 50% glucose solution infusion; n = 6). After LPS administration, blood glucose was determined every 10 min and glucose infusion rates were adjusted in LPS-Eu cows to maintain euglycemia for 720 min. Blood samples were obtained 180, 360, 540, and 720 min postbolus for further analysis. Cows were milked 360 and 720 min postbolus. Blood glucose was increased 84% in LPS-administered cows for up to 150 min postbolus; thereafter, circulating glucose was decreased 30% in LPS-C relative to LPS-Eu and CON cows. Mild hyperthermia (+0.5°C) occurred between 30 and 90 min postbolus in LPS-administered relative to CON cows; thereafter, rectal temperature did not differ between treatments. Milk yield and lactose percentage were decreased 80 and 11%, respectively, in LPS-administered relative to CON cows. Circulating insulin was increased 4 fold and nonesterified fatty acids, β-hydroxybutyrate, and ionized Ca were decreased ∼50% in LPS-administered compared with CON cows. Plasma l-lactate, haptoglobin, and serum amyloid A increased ∼160, 260, and 75%, respectively, in LPS-administered relative to CON cows. Overall, LPS-binding protein was increased 87% in LPS-administered relative to CON cows; however, at 720 min, it was decreased 25% in LPS-Eu compared with LPS-C cows. White blood cell count decreased ∼90% in LPS-administered cows at 180 min and progressively increased to ∼50% of CON values by 720 min. Total glucose deficit during the 720 min following LPS administration was calculated as the decrease in the amount of glucose required to synthesize milk (due to the decrease in milk yield relative to prebolus levels) plus the amount of glucose infused to maintain euglycemia (in LPS-Eu cows only) and was 461, 1,259, and 1,553 g for CON, LPS-C, and LPS-Eu cows, respectively. Our data indicate an acutely activated immune system uses >1 kg of glucose within 720 min and maintaining euglycemia did not rescue milk synthesis.

Heat stress (HS) decreases milk protein synthesis beyond what would be expected based on the concomitant reduction in feed intake. The aim of the present study was to evaluate the direct effects of HS on milk protein production. Four multiparous, lactating Holstein cows (101 ± 10 d in milk, 574 ± 36 kg of body weight, 38 ± 2 kg of milk/d) were individually housed in environmental chambers and randomly allocated to 1 of 2 groups in a crossover design. The study was divided into 2 periods with 2 identical experimental phases (control phase and trial phase) within each period. During phase 1 or control phase (9 d), all cows were housed in thermal neutral conditions (TN; 20°C, 55% humidity) and fed ad libitum. During phase 2 or treatment phase (9 d), group 1 was exposed to cyclical HS conditions (32 to 36°C, 40% humidity) and fed ad libitum, whereas group 2 remained in TN conditions but was pair-fed (PFTN) to their HS counterparts to eliminate the confounding effects of dissimilar feed intake. After a 30-d washout period in TN conditions, the study was repeated (period 2), inverting the environmental treatments of the groups relative to period 1: group 2 was exposed to HS and group 1 to PFTN conditions. Compared with PFTN conditions, HS decreased milk yield (17.0%), milk protein (4.1%), milk protein yield (19%), 4% fat-corrected milk (23%), and fat yield (19%). Apparent digestibility of dry matter, organic matter, neutral detergent fiber, acid detergent fiber, crude protein, and ether extract was increased (11.1-42.9%) in HS cows, as well as rumen liquor ammonia (before feeding 33.2%; after feeding 29.5%) and volatile fatty acid concentration (45.3%) before feeding. In addition, ruminal pH was reduced (9.5 and 6% before and after feeding, respectively) during HS. Heat stress decreased plasma free amino acids (AA; 17.1%) and tended to increase and increased blood, urine, and milk urea nitrogen (17.2, 243, and 24.5%, respectively). Further, HS cows had reduced plasma glucose (8%) and nonesterified fatty acid (39.8%) concentrations compared with PFTN controls. These data suggest that HS increases systemic AA utilization (e.g., decreased plasma AA and increased nitrogen excretion), a scenario that limits the AA supply to the mammary gland for milk protein synthesis. Furthermore, the increase in AA requirements during HS might represent the increased need for gluconeogenic precursors, as HS is thought to prioritize glucose utilization as a fuel at the expense of nonesterified fatty acids.

Acute heat stress (HS) and heat stroke can be detrimental to the health, well-being, and performance of mammals such as swine. Therefore, our objective was to chronologically characterize how a growing pig perceives and initially copes with a severe heat load. Crossbred gilts (n = 32; 63.8 ± 2.9 kg) were subjected to HS conditions (37°C and 40% humidity) with ad libitum intake for 0, 2, 4, or 6 h (n = 8/time point). Rectal temperature (T_r), respiration rates (RR), and feed intake were determined every 2 h. Pigs were euthanized at each time point and fresh ileum and colon samples were mounted into modified Ussing chambers to assess ex vivo intestinal integrity and function. Transepithelial electrical resistance (TER) and fluorescein isothiocyanate–labeled dextran (FD4) permeability were assessed. As expected, T_r increased linearly over time (P < 0.001) with the highest temperature observed at 6 h of HS. Compared to the 0-h thermal-neutral (TN) pigs, RR increased (230%; P < 0.001) in the first 2 h and remained elevated over the 6 h of HS (P < 0.05). Feed intake was dramatically reduced due to HS and this corresponded with significant changes in plasma glucose, ghrelin, and glucose-dependent insulinotropic peptide (P < 0.050). At as early as 2 h of HS, ileum TER linearly decreased (P < 0.01), while FD4 linearly increased with time (P < 0.05). Colon TER and FD4 changed due to HS in quadratic responses over time (P = 0.050) similar to the ileum but were less pronounced. In response to HS, ileum and colon heat shock protein (HSP) 70 mRNA and protein abundance increased linearly over time (P < 0.050). Altogether, these data indicated that a short duration of HS (2–6 h) compromised feed intake and intestinal integrity in growing pigs. Copyright © 2014. American Society of Animal Science .

Dietary zinc (inorganic and organic or zinc AA complex forms) is essential for normal intestinal barrier function and regeneration of intestinal epithelium. Given that heat stress (HS) exposure can negatively affect intestinal integrity and caloric intake, possible nutritional mitigation strategies are needed to improve health, performance, and well-being. Therefore, our objective was to evaluate 2 dietary zinc sources and reduced caloric intake on intestinal integrity in growing pigs subjected to 12 h of HS. A total of 36 pigs were fed 1 of 2 diets: 1) a control diet (CON; 120 mg/kg of zinc from zinc sulfate) or 2) 60 mg/kg from zinc sulfate and 60 mg/kg from zinc AA complex (ZnAA). After 17 d, the CON pigs were then exposed to thermal neutral (TN) conditions with ad libitum intake (TN-CON), HS (37°C) with ad libitum intake (HS-CON), or pair-fed to HS intake under TN conditions (PFTN); the ZnAA pigs were exposed to only HS (HS-ZnAA). All pigs were sacrificed after 12 h of environmental exposure, and blood and tissue bioenergetics stress markers and ex vivo ileum and colon integrity were assessed. Compared with TN-CON, HS significantly (P < 0.05) increased rectal temperatures and respiration rates. Ileum villus and crypt morphology was reduced by both pair-feeding and HS. Both PFTN and HS-CON pigs also had reduced ileum integrity (dextran flux and transepithelial resistance) compared with the TN-CON pigs. However, ZnAA tended to mitigate the HS-induced changes in ileum integrity. Ileum mucin 2 protein abundance was increased due to HS and pair-feeding. Colonic integrity did not differ due to HS or PFTN treatments. Compared with the HS-CON, HS-ZnAA pigs tended to have reduced blood endotoxin concentrations. In conclusion, HS and reduced feed intake compromised intestinal integrity in pigs, and zinc AA complex source mitigates some of these negative effects.

Heat stress (HS) jeopardizes human and animal health and reduces animal agriculture productivity; however, its pathophysiology is not well understood. Study objectives were to evaluate the direct effects of HS on carbohydrate and lipid metabolism. Female pigs (57 ± 5 kg body weight) were subjected to two experimental periods. During period 1, all pigs remained in thermoneutral conditions (TN; 20°C) and were ad libitum fed. During period 2, pigs were exposed to: (1) constant HS conditions (32°C) and fed ad libitum ( n = 7), or (2) TN conditions and pair‐fed (PFTN; n = 10) to minimize the confounding effects of dissimilar feed intake. All pigs received an intravenous glucose tolerance test (GTT) and an epinephrine challenge (EC) in period 1, and during the early and late phases of period 2. After 8 days of environmental exposure, all pigs were killed and tissue samples were collected. Despite a similar reduction in feed intake (39%), HS pigs tended to have decreased circulating nonesterified fatty acids (NEFA; 20%) and a blunted NEFA response (71%) to the EC compared to PFTN pigs. During early exposure, HS increased basal circulating C‐peptide (55%) and decreased the insulinogenic index (45%) in response to the GTT. Heat‐stressed pigs had a reduced T3 to T4 ratio (56%) and hepatic 5′‐deiodinase activity (58%). After 8 days, HS decreased or tended to decrease the expression of genes involved in oxidative phosphorylation in liver and skeletal muscle, and ATGL in adipose tissue. In summary, HS markedly alters both lipid and carbohydrate metabolism independently of nutrient intake.

Study objectives were to evaluate the effects of intentionally reduced intestinal barrier function on productivity, metabolism, and inflammatory indices in otherwise healthy dairy cows. Fourteen lactating Holstein cows (parity 2.6 ± 0.3; 117 ± 18 d in milk) were enrolled in 2 experimental periods. Period 1 (5 d) served as the baseline for period 2 (7 d), during which cows received 1 of 2 i.v. treatments twice per day: sterile saline or a gamma-secretase inhibitor (GSI; 1.5 mg/kg of body weight). Gamma-secretase inhibitors reduce intestinal barrier function by inhibiting crypt cell differentiation into absorptive enterocytes. During period 2, control cows receiving sterile saline were pair-fed (PF) to the GSI-treated cows, and all cows were killed at the end of period 2. Administering GSI increased goblet cell area 218, 70, and 28% in jejunum, ileum, and colon, respectively. In the jejunum, GSI-treated cows had increased crypt depth and reduced villus height, villus height-to-crypt depth ratio, cell proliferation, and mucosal surface area. Plasma lipopolysaccharide binding protein increased with time, and tended to be increased 42% in GSI-treated cows relative to PF controls on d 5 to 7. Circulating haptoglobin and serum amyloid A concentrations increased (585- and 4.4-fold, respectively) similarly in both treatments. Administering GSI progressively reduced dry matter intake (66%) and, by design, the pattern and magnitude of decreased nutrient intake was similar in PF controls. A similar progressive decrease (42%) in milk yield occurred in both treatments, but we observed no treatment effects on milk components. Cows treated with GSI tended to have increased plasma insulin (68%) and decreased circulating nonesterified fatty acids (29%) compared with PF cows. For both treatments, plasma glucose decreased with time while β-hydroxybutyrate progressively increased. Liver triglycerides increased 221% from period 1 to sacrifice in both treatments. No differences were detected in liver weight, liver moisture, or body weight change. Intentionally compromising intestinal barrier function caused inflammation, altered metabolism, and markedly reduced feed intake and milk yield. Further, we demonstrated that progressive feed reduction appeared to cause leaky gut and inflammation.