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Objectives were to determine the effects of a product containing electrolytes, osmolytes, and energetic compounds (EOEC) on body temperature indices in heat-stressed (HS) Holstein cows. Lactating cows were assigned to 1 of 2 treatments: 1) a control diet (n = 10) or 2) a control diet supplemented with 113 g/d of EOEC (n = 10; Bovine BlueLite® Pellets; TechMix LLC, Stewart, MN). The trial consisted of 2 experimental periods (P). During P1 (4 d), cows were fed their respective treatments and housed in thermoneutral conditions. During P2 (4 d), HS was artificially induced using an electric heat blanket (EHB). Overall, HS markedly increased vaginal temperature (Tv), rectal temperature (Tr), skin temperature (Ts), and respiration rate (RR) (P .01). There were no dietary treatment differences in Tv, Tr, or RR; however, during P2 EOEC-supplemented cows had increased Ts (0.8 °C; P = .04). Compared to P1, HS decreased DMI and milk yield (45 and 27%, respectively, P .01) similarly amongst treatments. Relative to P1, circulating insulin decreased (41%; P = .04) in CON cows, whereas it remained unaffected in EOEC-supplemented cows, resulting in a 2-fold increase in EOEC compared with CON-fed cows (P .01) during P2. Relative to P1, HS increased circulating non-esterified fatty acids (NEFA; 63%; P .01). During P2, there tended to be a treatment by day interaction on circulating NEFA, as concentrations decreased from d 2 to 4 of P2 in EOEC-fed cows but continued to increase in CON cows. In summary, feeding EOEC altered some key aspects of energetic metabolism and increased Ts.

Periparturient hypocalcemia is a common metabolic disorder and it is ostensibly associated with negative health and production outcomes. Acute infection also markedly decreases circulating Ca, but the reasons for and consequences of it on physiological and immunological parameters are unknown. Objectives were to evaluate the effects of maintaining eucalcemia on production, metabolic, and immune variables following an intravenous lipopolysaccharide (LPS) challenge. Twelve multiparous lactating Holstein cows (717 ± 20 kg of body weight; 176 ± 34 d in milk; parity 3 ± 0.2) were enrolled in a study containing 2 experimental periods (P); during P1 (3 d), cows consumed feed ad libitum and baseline values were obtained. At the initiation of P2 (4 d), cows were randomly assigned to 1 of 2 treatments: (1) LPS administered (LPS-Con; 0.5 μg/kg of body weight LPS; n = 6) or (2) LPS administered + eucalcemic clamp (LPS-Ca; 0.5 μg/kg of body weight LPS; Ca infusion; n = 6). Cows were fasted for the first 12 h during P2. After LPS administration, ionized Ca was determined every 15 min for 6 h and every 30 min for an additional 6 h and intravenous Ca infusion was adjusted in LPS-Ca cows to maintain eucalcemia. Blood ionized Ca was decreased 23% for the first 12 h postbolus in LPS-Con cows, and by design, Ca infusion prevented hypocalcemia. To maintain eucalcemia for the 12 h, 13.7 g of Ca was infused. The total Ca deficit (including Ca not secreted into milk) accumulated over the 12 h was 10.4 and 20.2 g for the LPS-Con and LPS-Ca treatments, respectively. Mild hyperthermia (0.8°C) occurred for ∼6 h post-LPS administration relative to P1. From 6 to 7 h postbolus rectal temperature from LPS-Ca cows was increased (0.6°C) relative to LPS-Con cows. On d 1 of P2, milk yield decreased (61%) in both treatments relative to P1. Relative to LPS-Con cows, milk yield decreased (15%) in LPS-Ca cows during P2. Overall, circulating LPS-binding protein continuously increased postbolus, and at 24 h LPS-binding protein levels in LPS-Ca cows were increased (80%) relative to LPS-Con cows. During P2, serum amyloid A increased (4-fold) in both treatments relative to P1. Administering LPS initially decreased circulating neutrophils, then cell counts progressively increased with time. Calcium infusion decreased neutrophil counts (40%) from 9 to 12 h postbolus relative to LPS-Con cows. Neutrophil function, as assessed by oxidative burst and myeloperoxidase production, did not differ due to treatment. In summary, maintaining eucalcemia (via intravenous Ca infusion) during an immune challenge appeared to intensify inflammation and adversely affect lactation performance.

The efficacy of an electric heat blanket (EHB) has previously been confirmed as an alternative method to evaluate heat stress (HS). However, a pair-feeding design has not been used with the EHB model. Therefore, study objectives were to determine the contribution of the nutritional plane to altered metabolism and productivity during EHB-induced HS. Multiparous Holstein cows (n = 18; 140 ± 10 d in milk) were subjected to 2 experimental periods (P); during P1 (4 d), cows were in thermoneutral conditions with ad libitum feed intake. During P2 (4 d), cows were assigned to 1 of 2 treatments: (1) thermoneutral conditions and pair-fed (PF; n = 8) or (2) EHB-induced HS with ad libitum feed intake (n = 10). Overall, the EHB increased rectal temperature, vaginal temperature, skin temperature, and respiration rate (1.4°C, 1.3°C, 0.8°C, and 42 breaths/min, respectively) relative to PF cows. The EHB reduced dry matter intake (DMI; 47%) and, by design, PF cows had a similar pattern and extent of decreased DMI. Milk yield decreased in EHB and PF cows by 27.3% (12.1 kg) and 13.4% (5.4 kg), respectively, indicating that reduced DMI accounted for only ∼50% of decreased milk synthesis. Milk fat content tended to increase (19%) in the EHB group, whereas in the PF cows it remained similar relative to P1. During P2, milk protein and lactose contents tended to decrease or decreased (1.3 and 2.2%, respectively) in both EHB and PF groups. Milk urea nitrogen remained unchanged in PF controls but increased (34.2%) in EHB cows relative to P1. The EHB decreased blood partial pressure of CO2, total CO2, HCO3, and base excess levels (17, 16, 17, and 81%, respectively) compared with those in PF cows. During P2, the EHB and PF cows had similar decreases (4%) in plasma glucose content, but no differences in circulating insulin were detected. However, a group by day interaction was detected for plasma nonesterified fatty acids; levels progressively increased in PF controls but remained unaltered in the EHB cows. Blood urea nitrogen increased in the EHB cows (61%) compared with the PF controls. In summary, utilizing the EHB model indicated that reduced nutrient intake explains only about 50% of the decrease in milk yield during HS, and the postabsorptive changes in nutrient partitioning are similar to those obtained in climate-controlled chamber studies. Consequently, the EHB is a reasonable and economically feasible model to study environmental physiology of dairy cows.

Previous research revealed a potential effect of dietary trace mineral source on both ruminal and fecal microbiota. However, the effect of Zn source, specifically, has not previously been considered. Based on reported postruminal solubility, we hypothesized that Zn hydroxychloride would decrease

Lipopolysaccharide (LPS) administration causes immunoactivation, which negatively affects production and fertility, but experimental exposure via an acute bolus is unlikely to resemble natural infections. Thus, the objectives were to characterize effects of chronic endotoxemia on production parameters and follicular development in estrous-synchronized lactating cows. Eleven Holstein cows (169 ± 20 d in milk; 681 ± 16 kg of body weight) were acclimated to their environmental surroundings for 3 d and then enrolled in 2 experimental periods (P). During P1 (3 d) cows consumed feed ad libitum and baseline samples were obtained. During P2 (7 d), cows were assigned to continuous infusion of either (1) saline-infused and pair-fed (CON-PF; 40 mL/h of saline i.v.; n = 5) or (2) LPS infused and ad libitum fed (LPS-AL; Escherichia coli O55:B5; 0.017, 0.020, 0.026, 0.036, 0.055, 0.088, and 0.148 μg/kg of body weight/h i.v. on d 1 to 7, respectively; n = 6). Controls were pair-fed to the LPS-AL group to eliminate confounding effects of dissimilar nutrient intake. Infusing LPS temporally caused mild hyperthermia on d 1 to 3 (+0.49°C) relative to baseline. Dry matter intake of LPS-AL cows decreased (28%) on d 1 of P2, then progressively returned to baseline. Relative to baseline, milk yield from LPS-AL cows was decreased on d 1 of P2 (12%). No treatment differences were observed in milk yield during P2. Follicular growth, dominant follicle size, serum progesterone (P4), and follicular P4 and 17β-estradiol concentrations were similar between treatments. Serum 17β-estradiol tended to increase (115%) and serum amyloid A and LPS-binding protein were increased (118 and 40%, respectively) in LPS-AL relative to CON-PF cows. Compared with CON-PF, neutrophils in LPS-AL cows were initially increased (45%), then gradually decreased. In contrast, monocytes were initially decreased (40%) and progressively increased with time in the LPS-AL cows. Hepatic mRNA abundance of cytochrome P450 family 2 subfamily C (CYP2C) or CYP3A was not affected by LPS, nor was there a treatment effect on toll-like receptor 4 or LBP; however, acyloxyacyl hydrolase and RELA subunit of nuclear factor kappa B tended to be increased in LPS-AL cows. These data suggest lactating dairy cows become tolerant to chronic and exponentially increasing LPS infusion in terms of production and reproductive parameters.

Experimental objectives of this study were to characterize the systemic and intracellular metabolic response to continuous lipopolysaccharide (LPS) infusion in mid-lactation Holstein cows (169 ± 20 d in milk; 681 ± 16 kg of body weight). Following 3 d of acclimation, cows were enrolled in 2 experimental periods (P). During P1 (3 d), cows were fed ad libitum and baseline data were collected. In P2 (8 d), cows were assigned to 1 of 2 treatments: (1) saline-infused and pair-fed (CON-PF; i.v. sterile saline at 40 mL/h; n = 5) or (2) LPS-infused and fed ad libitum (LPS-AL; Escherichia coli O55:B5 at 0.017, 0.020, 0.026, 0.036, 0.055, 0.088, 0.148, and 0.148 µg/kg of body weight per hour for d 1 through 8, respectively; n = 6). During P2, CON-PF cows were pair-fed to LPS-AL cows to eliminate confounding effects of dissimilar nutrient intake. Blood samples were collected on d 1 and 2 of P1 and d 1, 3, 5, and 7 of P2. Following the P2 d 7 a.m. milking, adipose tissue, skeletal muscle, and liver biopsies were collected for reverse transcription quantitative PCR and Western blot analysis. To assess whole-body nutrient trafficking, an i.v. glucose tolerance test (GTT) was performed following the a.m. milking on P2 d 8; 4 h after the GTT, cows received an epinephrine challenge. During P2, there were no treatment differences in circulating glucose. Relative to P1, CON-PF cows had or tended to have decreased plasma β-hydroxybutyrate and insulin (29 and 47%, respectively) during P2, whereas neither variable changed in LPS-AL cows, leading to an overall increase in β-hydroxybutyrate and insulin (41 and 140%, respectively) relative to CON-PF cows. Circulating nonesterified fatty acids were increased from d 1 to 3 and subsequently decreased from d 3 to 7 in cows from both treatments. Blood urea nitrogen gradually decreased in CON-PF cows and increased in LPS-AL cows from d 1 to 5 of P2, resulting in an overall 25% increase in LPS-AL versus CON-PF cows. In response to the GTT, the glucose and insulin area under the curve were increased 33 and 56%, respectively, in LPS-AL compared with CON-PF cows; changes reflective of whole-body insulin resistance. However, protein abundance of insulin signaling markers within muscle, liver, and adipose tissue were similar between treatments. There were no observable treatment differences in the glucose or nonesterified fatty acids response to the epinephrine challenge. No treatment differences were observed in hepatic mRNA abundance of key gluconeogenic or lipid export enzymes. In conclusion, chronic LPS exposure altered multiple parameters of basal and stimulated metabolism, but did not appear to affect the molecular machinery evaluated herein.

Study objectives were to determine the effects of dietary live yeast (Saccharomyces cerevisiae strain CNCM I-4407; ActisafHR+; 0.25g/kg of feed; Phileo by Lesaffre, Milwaukee, WI) on growth performance and biomarkers of metabolism and inflammation in heat-stressed and nutrient-restricted pigs. Crossbred barrows (n = 96; 79 ± 1 kg body weight [BW]) were blocked by initial BW and randomly assigned to one of six dietary-environmental treatments: 1) thermoneutral (TN) and fed ad libitum the control diet (TNCon), 2) TN and fed ad libitum a yeast containing diet (TNYeast), 3) TN and pair-fed (PF) the control diet (PFCon), 4) TN and PF the yeast containing diet (PFYeast), 5) heat stress (HS) and fed ad libitum the control diet (HSCon), or 6) HS and fed ad libitum the yeast diet (HSYeast). Following 5 d of acclimation to individual pens, pigs were enrolled in two experimental periods (P). During P1 (7 d), pigs were housed in TN conditions (20 °C) and fed their respective dietary treatments ad libitum. During P2 (28 d), HSCon and HSYeast pigs were fed ad libitum and exposed to progressive cyclical HS (28–33 °C) while TN and PF pigs remained in TN conditions and were fed ad libitum or PF to their HSCon and HSYeast counterparts. Pigs exposed to HS had an overall increase in rectal temperature, skin temperature, and respiration rate compared to TN pigs (0.3 °C, 5.5 °C, and 23 breaths per minute, respectively; P < 0.01). During P2, average daily feed intake (ADFI) decreased in HS compared to TN pigs (30%; P < 0.01). Average daily gain and final BW decreased in HS relative to TN pigs (P < 0.01); however, no differences in feed efficiency (G:F) were observed between HS and TN treatments (P > 0.16). A tendency for decreased ADFI and increased G:F was observed in TNYeast relative to TNCon pigs (P < 0.10). Circulating insulin was similar between HS and TN pigs (P > 0.42). Triiodothyronine and thyroxine levels decreased in HS compared to TN treatments (~19% and 20%, respectively; P < 0.05). Plasma tumor necrosis factor-alpha (TNF-α) did not differ across treatments (P > 0.57) but tended to decrease in HSYeast relative to HSCon pigs (P = 0.09). In summary, dietary live yeast did not affect body temperature indices or growth performance and had minimal effects on biomarkers of metabolism; however, it tended to improve G:F under TN conditions and tended to reduce the proinflammatory mediator TNF-α during HS. Further research on the potential role of dietary live yeast in pigs during HS or nutrient restriction scenarios is warranted.

The progression from gestation into lactation represents the transition period, and it is accompanied by marked physiological, metabolic, and inflammatory adjustments. The entire lactation and a cow's opportunity to have an additional lactation are heavily dependent on how successfully she adapts during the periparturient period. Additionally, a disproportionate amount of health care and culling occurs early following parturition. Thus, lactation maladaptation has been a heavily researched area of dairy science for more than 50 yr. It was traditionally thought that excessive adipose tissue mobilization in large part dictated transition period success. Further, the magnitude of hypocalcemia has also been assumed to partly control whether a cow effectively navigates the first few months of lactation. The canon became that adipose tissue released nonesterified fatty acids (NEFA) and the resulting hepatic-derived ketones coupled with hypocalcemia lead to immune suppression, which is responsible for transition disorders (e.g., mastitis, metritis, retained placenta, poor fertility). In other words, the dogma evolved that these metabolites and hypocalcemia were causal to transition cow problems and that large efforts should be enlisted to prevent increased NEFA, hyperketonemia, and subclinical hypocalcemia. However, despite intensive academic and industry focus, the periparturient period remains a large hurdle to animal welfare, farm profitability, and dairy sustainability. Thus, it stands to reason that there are alternative explanations to periparturient failures. Recently, it has become firmly established that immune activation and the ipso facto inflammatory response are a normal component of transition cow biology. The origin of immune activation likely stems from the mammary gland, tissue trauma during parturition, and the gastrointestinal tract. If inflammation becomes pathological, it reduces feed intake and causes hypocalcemia. Our tenet is that immune system utilization of glucose and its induction of hypophagia are responsible for the extensive increase in NEFA and ketones, and this explains why they (and the severity of hypocalcemia) are correlated with poor health, production, and reproduction outcomes. In this review, we argue that changes in circulating NEFA, ketones, and calcium are simply reflective of either (1) normal homeorhetic adjustments that healthy, high-producing cows use to prioritize milk synthesis or (2) the consequence of immune activation and its sequelae.

Study objectives were to evaluate the effects of replacing 40 mg/kg of dietary Zn from Zn sulfate (ZS) with Zn amino acid complex (ZA; Zinpro Corporation, Eden Prairie, MN) on inflammation and intestinal integrity in heat-stressed and pair-fed (PF) ruminants. Forty Holstein steers (173.6 ± 4.9 kg) were randomly assigned to 1 of 5 dietary-environmental treatments: (1) thermoneutral (TN) ad libitum with 75 mg/kg of dry matter (DM) ZS (ZSCON); (2) TN pair-fed with 75 mg/kg DM ZS (ZSPF); (3) TN pair-fed with 40 mg/kg DM ZA and 35 mg/kg DM ZS (ZAPF); (4) heat stress (HS) ad libitum with 75 mg/kg DM ZS (ZSHS); and (5) HS ad libitum 40 mg/kg DM ZA and 35 mg/kg DM ZS (ZAHS). Before study initiation, calves were fed their respective diets for 21 d. Following the pre-feeding phase, steers were transferred into environmental chambers and were subjected to 2 successive experimental periods. During period 1 (5 d), all steers were fed their respective diets ad libitum and housed in TN conditions (20.2 ± 1.4°C, 30.4 ± 4.3% relative humidity). During period 2 (6 d), ZSHS and ZAHS steers were exposed to cyclical HS conditions (27.1 ± 1.5°C to 35.0 ± 2.9°C, 19.3 ± 3.5% relative humidity), whereas the ZSCON, ZSPF, and ZAPF steers remained in TN conditions and were fed ad libitum or pair-fed relative to their ZSHS and ZAHS counterparts. Overall, steers exposed to HS had markedly increased rectal temperature (0.83°C), respiration rate (26 breaths per min), and skin temperature (8.00°C) relative to TN treatments. Rectal temperature from ZAHS steers was decreased (0.24°C) on d 4 to 6 of HS relative to ZSHS steers. Regardless of diet, HS decreased DMI (18%) relative to ZSCON steers. Circulating glucose from HS and PF steers decreased (16%) relative to ZSCON steers. Heat stress and nutrient restriction increased circulating nonesterified fatty acids 2- and 3-fold, respectively, compared with ZSCON steers. Serum amyloid A increased ~2-fold in PF relative to ZSCON and HS steers. We detected no treatment effect on blood pH; however, ZAHS steers had increased HCO3 relative to ZSHS. Relative to ZSHS, ZAHS steers had increased jejunum villi height (25%), a tendency for increased ileum villi height (9%), and decreased duodenal villi width (16%). In summary, ZA supplementation has some beneficial effects on thermal indices, intestinal architecture characteristics, and biomarkers of leaky gut in heat-stressed steers, indicative of an ameliorated heat load, and thus may be a nutritional strategy to minimize negative consequences of HS.

Inflammation appears to be a predisposing factor and key component of hepatic steatosis in a variety of species. Objectives were to evaluate effects of inflammation [induced via intravenous lipopolysaccharide (LPS) infusion] on metabolism and liver lipid content in experimentally induced hyperlipidemic lactating cows. Cows (765 ± 32 kg of body weight; 273 ± 35 d in milk) were enrolled in 2 experimental periods (P); during P1 (5 d), baseline data were obtained. At the start of P2 (2 d), cows were assigned to 1 of 2 treatments: (1) intralipid plus control (IL-CON; 3 mL of saline; n = 5) or (2) intralipid plus LPS (IL-LPS; 0.375 μg of LPS/kg of body weight; n = 5). Directly following intravenous bolus (saline or LPS) administration, intralipid (20% fat emulsion) was intravenously infused continuously (200 mL/h) for 16 h to induce hyperlipidemia during which feed was removed. Blood samples were collected at -0.5, 0, 4, 8, 12, 16, 24, and 48 h relative to bolus administration, and liver biopsies were obtained on d 1 of P1 and at 16 and 48 h after the bolus. By experimental design (feed was removed during the first 16 h of d 1), dry matter intake decreased in both treatments on d 1 of P2, but the magnitude of reduction was greater in LPS cows. Dry matter intake of IL-LPS remained decreased on d 2 of P2, whereas IL-CON cows returned to baseline. Milk yield decreased in both treatments during P2, but the extent and duration was longer in LPS-infused cows. Administering LPS increased circulating LPS-binding protein (2-fold) at 8 h after bolus, after which it markedly decreased (84%) below baseline for the remainder of P2. Serum amyloid A concentrations progressively increased throughout P2 in IL-LPS cows (3-fold, relative to controls). Lipid infusion gradually increased nonesterified fatty acids and triglycerides in both treatments relative to baseline (3- and 2.5-fold, respectively). Interestingly, LPS infusion blunted the peak in nonesterified fatty acids, such that concentrations peaked (43%) higher in IL-CON compared with IL-LPS cows and heightened the increase in serum triglycerides (1.5-fold greater relative to controls). Liver fat content remained similar in IL-LPS relative to P1 at 16 h; however, hyperlipidemia alone (IL-CON) increased liver fat (36% relative to P1). No treatment differences in liver fat were observed at 48 h. In IL-LPS cows, circulating insulin increased markedly at 4 h after bolus (2-fold relative to IL-CON), and then gradually decreased during the 16 h of lipid infusion. Inducing inflammation with simultaneous hyperlipidemia altered the characteristic patterns of insulin and LPS-binding protein but did not cause fatty liver.

Study objectives were to determine the effects of zinc (Zn) amino acid complex (Availa Zn, Zinpro Corporation, Eden Prairie, MN) on metabolism, biomarkers of leaky gut, and inflammation during and following heat stress (HS) and nutrient restriction. Crossbred gilts (n = 50; 50 ± 2 kg BW) were blocked by initial BW and randomly assigned to one of five treatments: 1) thermoneutral (TN) and ad libitum fed a control diet (TNCtl), 2) TN and pair-fed a control diet (PFCtl), 3) TN and pair-fed a Zn-supplemented diet (PFZn), 4) HS and ad libitum fed a control diet (HSCtl), and 5) HS and ad libitum fed a Zn-supplemented diet (HSZn). The study consisted of 3 experimental periods (P): during P1 (7 d), all pigs were fed their respective diets ad libitum and housed in TN conditions (20.84 ± 0.03 °C, 47.11 ± 0.42% relative humidity). During P2 (7 d), HSCtl and HSZn pigs were exposed to progressive cyclical HS conditions (27 to 30 °C, 41.9 ± 0.5% relative humidity), while TNCtl, PFCtl, and PFZn pigs remained in TN conditions and were fed ad libitum or pair-fed to their respective HSCtl and HSZn counterparts. During P3 (5 d; "recovery phase"), all pigs were housed in TN conditions and fed ad libitum. Pigs exposed to HS had overall increased rectal temperature, skin temperature, and respiration rate (0.33 °C, 3.76 °C, and 27 bpm, respectively; P 0.10). In summary, Zn reduced TNFα (regardless of HS), and the stimulatory effect of HS on insulin secretion is amplified during HS recovery.

Inadequate feed consumption reduces intestinal barrier function in both ruminants and monogastrics. Objectives were to characterize how progressive feed restriction (FR) affects inflammation, metabolism, and intestinal morphology, and to investigate if glucagon-like peptide 2 (GLP2) administration influences the aforementioned responses. Twenty-eight Holstein cows (157 ± 9 d in milk) were enrolled in 2 experimental periods. Period 1 [5 d of ad libitum (AL) feed intake] served as baseline for period 2 (5 d), during which cows received 1 of 6 treatments: (1) 100% of AL feed intake (AL100; n = 3), (2) 80% of AL feed intake (n = 5), (3) 60% of AL feed intake (n = 5), (4) 40% of AL feed intake (AL40; n = 5), (5) 40% of AL feed intake + GLP2 administration (AL40G; 75 µg/kg of BW s.c. 2×/d; n = 5), or (6) 20% of AL feed intake (n = 5). As the magnitude of FR increased, body weight and milk yield decreased linearly. Blood urea nitrogen and insulin decreased, whereas nonesterified fatty acids and liver triglyceride content increased linearly with progressive FR. Circulating endotoxin, lipopolysaccharide binding protein, haptoglobin, serum amyloid A, and lymphocytes increased or tended to increase linearly with advancing FR. Circulating haptoglobin decreased (76%) and serum amyloid A tended to decrease (57%) in AL40G relative to AL40 cows. Cows in AL100, AL40, and AL40G treatments were euthanized to evaluate intestinal histology. Jejunum villus width, crypt depth, and goblet cell area, as well as ileum villus height, crypt depth, and goblet cell area, were reduced (36, 14, 52, 22, 28, and 25%, respectively) in AL40 cows compared with AL100 controls. Ileum cellular proliferation tended to be decreased (14%) in AL40 versus AL100 cows. Relative to AL40, AL40G cows had improved jejunum and ileum morphology, including increased villus height (46 and 51%), villus height to crypt depth ratio (38 and 35%), mucosal surface area (30 and 27%), cellular proliferation (43 and 36%), and goblet cell area (59 and 41%). Colon goblet cell area was also increased (48%) in AL40G relative to AL40 cows. In summary, progressive FR increased circulating markers of inflammation, which we speculate is due to increased intestinal permeability as demonstrated by changes in intestinal architecture. Furthermore, GLP2 improved intestinal morphology and ameliorated circulating markers of inflammation. Consequently, FR is a viable model to study consequences of intestinal barrier dysfunction and administering GLP2 appears to be an effective mitigation strategy to improve gut health.

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.

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.

Objectives were to evaluate the effects of an oral supplement containing soluble Ca, and live yeast in LPS-challenged dairy cows. The trial consisted of 2 experimental periods (P). During P1 (3 d), cows (n = 12) were fed ad libitum and baseline data was collected. At the beginning of P2 (which lasted 96 h), all cows were i.v. challenged with 0.375 μg/kg BW LPS. Cows were assigned randomly to 1 of 2 treatments: 1) control (CON; no bolus; n = 6) or 2) an oral bolus containing Ca and live yeast (CLY; YMCP Vitall® 44.718 g of elemental Ca; TechMix, LLC., Stewart, MN; n = 6), administered -0.5 and 6.5 h relative to LPS infusion. Following LPS administration, circulating Ca decreased in both treatments but supplemental CLY ameliorated the hypocalcemia (48 h area under the curve: -10.8 vs. -1.9 mmol/L × h; P .01). Lipopolysaccharide decreased dry matter intake (DMI; 60%) similarly for both treatments on d 1, but overall (d 1-4) DMI tended to be reduced less (14 vs. 30%; P = .06) in CLY supplemented vs CON cows. Lipopolysaccharide reduced milk yield (70%; P .01) from 12 to 24 h, but throughout P2, milk yield from CLY supplemented cows was increased (38%; P = .03) relative to CON cows. Overall during P2, circulating LPS-binding protein and serum amyloid A increased post LPS (3- and 4-fold, respectively, P .01), but were unaffected by treatment (P ≥ .68). In conclusion, providing an oral supplement containing Ca and live yeast prior to and following LPS administration markedly ameliorated LPS-induced hypocalcemia and improved DMI and milk yield.

Heat stress (HS) negatively impacts production parameters, including milk yield and composition, growth and reproduction. Precisely studying HS typically requires expensive climate-controlled facilities, resources often inaccessible to most scientists. Therefore, we evaluated the efficacy of using an electric heat blanket (EHB) as an alternative and cost-effective method to study HS and determine whether EHB-induced hyperthermia affects physiological and production parameters similar to natural HS. This was the first proof of concept study examining this model. Results indicated increased body temperature indices (i.e., rectal temperature and respiration rate) and reduced DMI and milk yield, as well as altered milk composition similar to natural and climate-controlled HS studies. In experiment 2, we examined the EHB model in combination with a pair-feeding (PF) design. By employing the PF design, we clearly illustrated that a lowered nutritional plane explains only approximately 50% of the decreased milk yield in HS cows, with the remaining portion due to changes in post-absorptive changes in nutritional physiology. In addition, the EHB blunted adipose tissue mobilization and increased plasma biomarkers of muscle catabolism. Results from this study validated that the EHB is a valid model to study HS; therefore, experiment 3 was designed to assess nutritional HS mitigation strategies using the EHB model. Dietary electrolyte, osmolyte, and energetic compounds (EOEC) were evaluated as re-hydration therapy on body temperature indices in HS lactating Holstein cows. Skin temperature was increased in EOEC-supplemented cows relative to controls which suggests that EOEC increased heat dissipation. In addition, EOEC-supplemented cows had increased glucose and insulin levels compared with controls which is due to the energetic compounds (i.e., dextrose) present in the EOEC supplement. Collectively, employing EHB model provides an excellent new platform for discovery research and evaluating pragmatic HS mitigation strategies.

Circulating serotonin (5-hydroxytryptamine; 5-HT) appears to be associated with various energetic disorders and hypocalcemia during the transition period. The objective of this study was to evaluate the effects of ketosis, feed restriction (FR), and endotoxin challenge (models in which energetic and calcium metabolism are markedly altered) on circulating 5-HT in lactating Holstein cows. Blood samples were obtained from 3 separate experiments; circulating β-hydroxybutyrate (BHB), nonesterified fatty acids (NEFA), and glucose were measured in all 3 experiments, whereas ionized calcium (iCa2+) was measured only in the endotoxin challenge. In the ketosis study, blood samples from cows clinically diagnosed with ketosis (n = 9) or classified as healthy (n = 9) were obtained from a commercial dairy farm at d -7, 3, and 7 relative to calving. Ketosis was diagnosed using a urine-based test starting at 5 d in milk. There was no effect of health status on circulating 5-HT and no association between 5-HT and BHB, NEFA, or glucose; however, 5-HT concentrations progressively decreased following calving. In the FR experiment, mid-lactation cows were either fed ad libitum (n = 3) or restricted to 20% of their ad libitum intake (n = 5) for 5 d. There were no FR effects on circulating 5-HT, nor was FR correlated with energetic metabolites. In the immune activation model, mid-lactation cows were intravenously challenged with either lipopolysaccharide (LPS; 1.5 µg/kg of BW; n = 6) or sterile saline (control; n = 6). Administering LPS decreased (56%) blood iCa2+ but had no effect on circulating 5-HT, nor was there a correlation between circulating 5-HT and NEFA, BHB, or iCa2+. Circulating 5-HT tended to be positively correlated (r = 0.54) with glucose in Holstein cows administered LPS. In summary, in contrast to expectations, circulating 5-HT was unaffected in models of severely disturbed energetic and Ca2+ homeostasis.

Ketosis is a prevalent periparturient metabolic disorder and we hypothesize that lipopolysaccharide (LPS) infiltration may play a key role in its etiology. Study objectives were to characterize biomarkers of inflammation during the transition period in healthy and clinically diagnosed ketotic cows. Cows were retrospectively categorized into one of two groups: healthy and clinically diagnosed ketotic. Two data sets were utilized; the first dataset (Study A) was obtained as a subset of cows (n=16) enrolled in a larger experiment conducted at the Iowa State University Dairy utilizing Holstein cows (8 healthy; 8 ketotic), and the second dataset (Study B; 22 healthy; 22 ketotic) was obtained from a commercial farm. For both experiments, blood samples were collected prior to and following calving. Ketotic cows in both studies had reduced milk production compared to healthy cows (P0.01). Post-calving, ketotic cows had increased serum amyloid A (4.2 and 1.8 fold in studies A and B, respectively; P=0.03 and P=0.04), haptoglobin (6 fold and ~4 fold; P=0.04 and P=0.03), and lipopolysaccharide binding protein (66 and 45%; P0.01 and P=0.02) compared with their healthy counterparts. Antepartum circulating LPS in ketotic cows was increased (2.3 fold; P=0.01) compared to healthy cows in Study B. In summary, increased biomarkers of inflammation appear to be closely associated with ketosis in transition dairy cows.

Study objectives were to determine the effects of chromium (Cr) propionate (Cr propionate 0.04%; 0.5 g/kg of feed to deliver 200 parts per billion Cr/d; KemTRACE Cr, Kemin Industries, Inc., Des Moines, IA) on growth performance, metabolism, and health biomarkers in heat-stressed and nutrient-restricted pigs. Crossbred barrows (n = 96; 105 ± 1 kg BW) were enlisted in an experiment conducted in two replicates, blocked by initial BW, and randomly assigned to one of six dietary-environmental treatments: (i) thermoneutral (TN) and fed ad libitum a control diet (TNCtl), (ii) TN and fed ad libitum a Cr supplemented diet (TNCr), (iii) TN and pair-fed a control diet (PFCtl), (iv) TN and pair-fed a Cr supplemented diet (PFCr), (v) heat stress (HS) and ad libitum fed a control diet (HSCtl), or (vi) HS and ad libitum fed a Cr supplemented diet (HSCr). The study consisted of three experimental periods (P). During P0 (5 d), all pigs were housed in TN conditions (21.3 ± 0.1 °C, 56.8 ± 0.3% relative humidity [RH]) and fed the control diet ad libitum. During P1 (5 d), pigs were fed their respective dietary treatments ad libitum and kept in TN conditions. During P2 (35 d), HSCtl and HSCr-treated pigs were fed ad libitum and exposed to progressive cyclical HS conditions (27 to 31 °C, 50 ± 0.3% RH), while TNCtl, TNCr, PFCtl, and PFCr pigs remained in TN conditions and were fed ad libitum or pair-fed to their respective HSCtl and HSCr counterparts to eliminate the confounding effects of dissimilar feed intake. Overall, HS pigs had increased (P < 0.01) rectal temperature, skin temperature, and respiration rate (0.3 °C, 3.8 °C, and 32 breaths per minute, respectively) relative to TN pigs. Overall, HS decreased ADFI and ADG (20 and 21%, respectively; P < 0.01) compared with TN controls. Final BW tended to be increased in HSCr (2.7 kg, P = 0.06) compared with HSCtl pigs. Similarly, ADG tended to be increased during P2 in HSCr relative to HSCtl-treatment (0.77 vs. 0.72 kg/d; P = 0.10). There were no effects of Cr on most production parameters, but ADFI tended to be increased in Cr relative to Ctl-fed pigs (3.19 vs. 3.09 kg/d; P = 0.08). No effects of Cr supplementation were detected on circulating glucose, insulin, NEFA, cholesterol, triglycerides, or lipopolysaccharide binding protein. However, blood neutrophils were increased in HSCr (37%; P < 0.01) relative to HSCtl pigs. In summary, these results suggest Cr supplementation may benefit growth performance during HS.

Heat stress (HS) jeopardizes animal productivity and health. The intestinal barrier is sensitive to HS and heat-induced hyperpermeability plays a key role in its pathophysiology. However, the biology of recovery following HS is less understood. Thus, study objectives were to determine the temporal pattern of metabolic, inflammatory, and intestinal histological parameters during HS recovery. Female pigs (n = 32; 19.5 ± 0.5 kg BW) were sacrificed following exposure to 1 of 4 environmental treatments: 1) constant thermoneutral (TN) conditions (TNC; 24.2 ± 0.5°C), 2) no TN recovery post HS (0D), 3) 3 d of TN recovery post HS (3D), and 4) 7 d of TN recovery post HS (7D). The HS protocol was cyclical (33.6 ± 1.8 to 37.4 ± 2.1°C) and lasted for 3 d for all HS treatments. During the 3 d of HS, rectal temperature, skin temperature, and respiration rates were increased (1.3°C, 4.8°C, and 77 breaths/min, respectively; P < 0.01) and ADFI was decreased (27%; P < 0.01) compared to TNC pigs. Skin temperature tended to be decreased 0.6°C in 3D pigs during days 1-3 of recovery (P = 0.06) and was decreased 1.6 and 0.7°C during days 1-3 and 4-7 of recovery, respectively, in 7D pigs (P ≤ 0.03) compared to TNC. Relative to TNC pigs, ADFI remained 14% decreased during days 1-3 of recovery in both 3D and 7D pigs, and 17% decreased during days 4-7 in 7D pigs (P ≤ 0.01). Plasma glucose was decreased (10%; P = 0.03) for 0D and 3D relative to TNC pigs. Circulating lipopolysaccharide-binding protein was increased in 3D and 7D vs. TNC pigs (110 and 147%, respectively; P = 0.01) and tended to increase linearly with increasing recovery time (P = 0.08). Circulating tumor necrosis factor alpha was decreased (15%) in 0D pigs and increased linearly with advancing recovery time (P < 0.01). Jejunum and ileum villus height were reduced 17 and 11% in 0D vs. TNC pigs and increased linearly with progressive recovery time (P < 0.01). Jejunum and ileum mucosal surface areas were reduced 17 and 9% in 0D pigs and remained decreased in the jejunum while the ileum recovered to TNC levels by day 3 of recovery. Relative to TNC pigs, goblet cell area was similar in jejunum and colon of 0D pigs but was reduced in the ileum of 0D pigs and in jejunum, ileum, and colon of 3D and 7D relative to TNC pigs (P < 0.01). In summary, HS has deleterious effects on intestinal morphology that seem to improve with recovery time. In contrast, feed consumption remained suppressed and inflammatory biomarkers indicative of leaky gut increased following the heat load.

Precisely studying the biological consequences of heat stress (HS) in agriculturally relevant animals typically requires expensive climate-controlled facilities, infrastructure inaccessible to most researchers. Thus, study objectives were to explore the efficacy of an electric heat blanket (EHB) as an alternative method for evaluating HS and to determine whether EHB-induced hyperthermia affects production parameters similar to natural HS. Lactating Holstein cows (n = 8; 133 ± 3 d in milk; 709 ± 31 kg; 2.6 ± 0.3 parity) were housed in individual box stalls and allowed to acclimate for 3 d. After acclimation, the trial consisted of 2 experimental periods (P). During P1 (3 d), cows were housed in thermoneutral conditions for collecting baseline data. During P2 (7 d), cows were fitted with an EHB. During the entire experiment cows were fed ad libitum, and dry matter intake (DMI) was recorded daily. Cows were milked twice daily (0600 and 1800 h), and milk samples were collected on d 2 and 3 of P1 and d 3 and 7 of P2. Rectal temperature, respiration rate, heart rate, and skin temperature were obtained twice daily (0600 and 1800 h) during both P1 and P2. Overall, there was an increase in rectal temperature and respiration rate at 0600 h (1.0°C and 25 breaths/min, respectively) and 1800 h (1.2°C and 29 breaths/min, respectively) during P2. The EHB decreased DMI and milk yield (25 and 21%, respectively) by the end of P2. During P2, milk protein tended to decrease (4.4%) compared with P1. In contrast, milk urea nitrogen increased (33%) during P2 relative to P1. No other differences were observed in milk composition. In summary, our results indicate that employing an EHB affects physiological and production parameters similarly to natural HS (i.e., increased rectal temperature and respiration rate, decreased DMI and milk yield); thus, the EHB is an effective and inexpensive research tool for evaluating the biological consequences of HS in lactating dairy cows.

Heat stress (HS) negatively impacts several swine production variables, including carcass fat quality and quantity. Pigs reared in HS have more adipose tissue than energetically predicted, explainable, in part, by HS-induced hyperinsulinemia. Study objectives were to evaluate insulin’s role in altering fat characteristics during HS via feeding insulin-sensitizing compounds. Forty crossbred barrows (113 ± 9 kg BW) were randomly assigned to one of five environment by diet treatments: 1) thermoneutral (TN) fed ad libitum (TNAL), 2) TN and pair-fed (TNPF), 3) HS fed ad libitum (HSAL), 4) HS fed ad libitum with sterculic oil (SO) supplementation (HSSO; 13 g/d), and 5) HS fed ad libitum with dietary chromium (Cr) supplementation (HSCr; 0.5 mg/d; Kemin Industries, Des Moines, IA). The study consisted of three experimental periods (P). During P0 (2 d), all pigs were exposed to TN conditions (23 ± 3 °C, 68 ± 10% RH) and fed ad libitum. During P1 (7 d), all pigs received their respective dietary supplements, were maintained in TN conditions, and fed ad libitum. During P2 (21 d), HSAL, HSSO, and HSCr pigs were fed ad libitum and exposed to cyclical HS conditions (28 to 33 °C, 58 ± 10% RH). The TNAL and TNPF pigs remained in TN conditions and were fed ad libitum or pair-fed to their HSAL counterparts. Rectal temperature (T(R)), respiration rate (RR), and skin temperature (T(S)) were obtained daily at 0600 and 1800 h. At 1800 h, HS exposed pigs had increased T(R), RR, and T(S) relative to TNAL controls (1.13 °C, 48 bpm, and 3.51 °C, respectively; P < 0.01). During wk 2 and 3 of P2, HSSO pigs had increased 1800 h T(R) relative to HSAL and HSCr (~0.40 and ~0.42 °C, respectively; P ≤ 0.05). Heat stress decreased ADFI and ADG compared to TNAL pigs (2.24 vs. 3.28 and 0.63 vs. 1.09 kg/d, respectively; P < 0.01) and neither variable was affected by SO or Cr supplementation. Heat stress increased or tended to increase moisture content of abdominal (7.7 vs. 5.9%; P = 0.07) and inner s.c. (11.4 vs. 9.8%; P < 0.05) adipose depots compared to TNAL controls. Interestingly, TNPF pigs also had increased adipose tissue moisture content and this was most pronounced in the outer s.c. depot (15.0 vs. 12.2%; P < 0.01) compared to TNAL pigs. Heat stress had little or no effect on fatty acid composition of abdominal, inner, and outer s.c. adipose tissue depots. In summary, the negative effects of HS on fat quality do not appear to be fatty acid composition related, but may be explained by increased adipose tissue moisture content.

Administrating lipopolysaccharide (LPS) decreases circulating calcium (Ca) and markedly reduces both feed intake and milk yield in lactating cows. Calcium is involved in immune system activation and live yeast can increase feed intake. Whether supplemental live yeast and Ca benefits immune-challenged cows remains unclear. Therefore, study objectives were to evaluate if providing an oral supplement containing soluble Ca, live yeast and other micronutrients would ameliorate LPS-induced hypocalcemia and production parameters in lactating dairy cows. Providing an oral supplement containing Ca and live yeast prior to and following LPS administration markedly ameliorated the LPS-induced hypocalcemia and improved DMI and milk yield. Overall, utilizing an oral supplement may be a valuable management strategy to improve animal welfare and productivity during and following immunoactivation. Additionally, infusing i.v. LPS appears to be an effective technique to model hypocalcemia and to evaluate dietary strategies aimed at increasing circulating calcium in lactating dairy cows.

Activated immune cells are insulin sensitive and utilize copious amounts of glucose. Because chromium (Cr) increases insulin sensitivity and may be immunomodulatory, our objective was to evaluate the effect of supplemental Cr (KemTrace Cr propionate, 20 g/d; Kemin Industries Inc., Des Moines, IA) on immune system glucose utilization and immune system dynamics following an intravenous endotoxin challenge in lactating Holstein cows. Twenty cows (320 ± 18 d in milk) were randomly assigned to 1 of 4 treatments: (1) pair-fed (PF) control (PF-CON; 5 mL of saline; n = 5), (2) PF and Cr supplemented (PF-Cr; 5 mL of saline; n = 5), (3) lipopolysaccharide (LPS)-euglycemic clamp and control supplemented (LPS-CON; 0.375 µg/kg of body weight LPS; n = 5), and (4) LPS-euglycemic clamp and Cr supplemented (LPS-Cr; 0.375 µg/kg of body weight LPS; n = 5). The experiment was conducted serially in 3 periods (P). During P1 (3 d), cows received their respective dietary treatments and baseline values were obtained. At the initiation of P2 (2 d), either a 12-h LPS-euglycemic clamp was conducted or cows were PF to their respective dietary counterparts. During P3 (3 d), cows consumed feed ad libitum and continued to receive their respective dietary treatment. During P2, LPS administration decreased dry matter intake (DMI; 40%) similarly among diets, and by experimental design the pattern and magnitude of reduced DMI were similar in the PF cohorts. During P3, LPS-Cr cows tended to have decreased DMI (6%) relative to LPS-CON cows. Relative to controls, milk yield from LPS-challenged cows decreased (58%) during P2 and LPS-Cr cows produced less (16%) milk than LPS-CON cows. During P3, milk yield progressively increased similarly in LPS-administered cows, but overall milk yield remained decreased (24%) compared with PF controls. There were no dietary treatment differences in milk yield during P3. Circulating insulin increased 9- and 15-fold in LPS-administered cows at 6 and 12 h postbolus, respectively, compared with PF controls. Compared with LPS-CON cows, circulating insulin in LPS-Cr cows was decreased (48%) at 6 h postbolus. Relative to PF cows, circulating LPS binding protein and serum amyloid A from LPS-administered cows increased 2- and 5-fold, respectively. Compared with PF cows, blood neutrophil counts in LPS-infused cows initially decreased, then gradually increased 163%. Between 18 and 48 h postbolus, the number of neutrophils was increased (12%) in LPS-Cr versus LPS-CON cows. The 12-h total glucose deficit was 220 and 1,777 g for the PF and LPS treatments, respectively, but glucose utilization following immune activation was not influenced by Cr. In summary, supplemental Cr reduced the insulin response and increased circulating neutrophils following an LPS challenge but did not appear to alter the immune system's glucose requirement following acute and intense activation.

Activated immune cells become obligate glucose utilizers, and a large i.v. lipopolysaccharide (LPS) dose causes insulin resistance and severe hypoglycemia. Therefore, study objectives were to quantify the amount of glucose needed to maintain euglycemia following an endotoxin challenge as a proxy of leukocyte glucose requirements. Fifteen fasted crossbred gilts (30.3 ± 1.7 kg) were bilaterally jugular catheter-ized and assigned 1 of 2 i.v. bolus treatments control (CON; 10 mL sterile saline; n = 7) or LPS challenge + euglycemic clamp (LPS-Eu; Escherichia coli 055B5; 5 μg/kg BW; 50% dextrose infusion to maintain euglycemia; n = 8). Following administration, blood glucose was determined every 10 min and dextrose infusion rates were adjusted in LPS-Eu pigs to maintain euglycemia for 8 h. Pigs were fasted for 8 h prior to the bolus and remained fasted throughout the challenge. Rectal temperature was increased in LPS-Eu pigs relative to CON pigs (39.8 vs. 38.8°C; P < 0.01). Relative to the baseline, CON pigs had 20% decreased blood glucose from 300 to 480 min postbolus (P = 0.01) whereas cir- culating glucose content in LPS-Eu pigs did not differ (P = 0.96) from prebolus levels. A total of 116 ± 8 g of infused glucose was required to maintain euglycemia in LPS-Eu pigs. Relative to CON pigs, overall plasma insulin, blood urea nitrogen, β-hydroxybutrate, l-lactate, and LPS-binding protein were increased in LPS-Eu pigs (295, 108, 29, 133, and 13%, respectively; P ≤ 0.04) whereas NEFA was decreased (66%; P < 0.01). Neutrophils in LPS-Eu pigs were decreased 84% at 120 min postbolus and returned to CON levels by 480 min (P < 0.01). Overall, lymphocytes, monocytes, eosinophils, and basophils were decreased in LPS-Eu pigs relative to CON pigs (75, 87, 70, and 50%, respectively; P ≤ 0.05). These alterations in metabolism and the large amount of glucose needed to maintain euglycemia indicate nutrient repartitioning away from growth toward the immune system. Glucose is an important fuel for the immune system, and data from this study established that the glucose requirements of an intensely and acutely activated immune system in growing pigs are approximately 1.1 g/kg BW0.75/h. © 2017 American Society of Animal Science. All rights reserved.

Infection and inflammation impede efficient animal productivity. The activated immune system ostensibly requires large amounts of energy and nutrients otherwise destined for synthesis of agriculturally relevant products. Accurately determining the immune system's in vivo energy needs is difficult, but a better understanding may facilitate developing nutritional strategies to maximize productivity. The study objective was to estimate immune system glucose requirements following an i.v. lipopolysaccharide (LPS) challenge. Holstein steers (148 ± 9 kg; = 15) were jugular catheterized bilaterally and assigned to 1 of 3 i.v. TREATMENTS control (CON; 3 mL saline; = 5), LPS-administered controls (LPS-C; 055:B5; 1.5 mg/kg BW; = 5), and LPS + euglycemic clamp (LPS-Eu; 1.5 mg/kg BW; 50% dextrose infusion to maintain euglycemia; = 5). In LPS-Eu steers, postbolus blood samples were analyzed for glucose every 10 min. Dextrose infusion rates were adjusted to maintain euglycemia for 720 min. All steers were fasted during the challenge. Samples for later analysis were obtained at 180, 360, 540, and 720 min relative to LPS administration. Rectal temperature was increased ∼0.5°C in both LPS treatments relative to CON steers ( = 0.01). Steers in both LPS treatments were hyperglycemic for ∼3 h postbolus; thereafter, blood glucose was markedly decreased (30%; < 0.01) in LPS-C relative to both CON and LPS-Eu steers. A total of 516 ± 65 g of infused glucose was required to maintain continuous euglycemia in LPS-Eu steers. Circulating insulin increased in LPS-C and LPS-Eu steers relative to CON (∼70% and ∼20 fold, respectively; < 0.01). Circulating NEFA increased similarly with time for both CON and LPS-C compared to LPS-Eu steers (∼43%; < 0.01). Plasma L-lactate and LPS binding protein increased (∼198 and ∼90%, respectively; < 0.01) and ionized calcium decreased (18%; < 0.01) in both LPS treatments relative to CON steers. Circulating white blood cells decreased initially in LPS-Eu and LPS-C relative to controls (180 min; 85%) followed by a progressive increase with time ( = 0.02). Blood neutrophils followed the same pattern; however, at 720 min, neutrophils were decreased in LPS-Eu compared to LPS-C, resulting in a decreased neutrophil-to-lymphocyte ratio (54%; = 0.03). The large amount of glucose needed to maintain euglycemia indicates extensive repartitioning of nutrients away from growth and the importance of glucose as a fuel for the immune system.