Plasma paraoxonase, health, inflammatory conditions, and liver function in transition dairy cows.

Paraoxonase (PON) is a liver protein with hydrolase activity that is released into the blood stream. Paraoxonase may serve as an index of liver function because it is drastically reduced in chronic liver damage. Sixty-seven periparturient dairy cows were used to evaluate the relationship between plasma PON, health problems, inflammatory conditions, and liver function. Baseline plasma PON concentrations during the first 30 d in milk (DIM) were retrospectively used to group cows into quartiles. Metabolic profile, lipid metabolites (e.g., nonesterified fatty acids, beta-hydroxybutyrate), inflammatory indices (haptoglobin, ceruloplasmin), low and high density lipoprotein cholesterol, vitamin A, vitamin E, reactive oxygen metabolites, total antioxidants, and PON in plasma were measured 2 wk before to 8 wk after calving. Weekly milk yield, body condition score, and all health problems were recorded. After parturition (7 DIM), cows in the lower PON group had the lowest plasma concentrations of negative acute phase proteins compared with the higher PON group for retinol binding protein (23.2 +/- 2.86 vs. 36.0 +/- 2.96 microg/dL of vitamin A), albumin (31.6 +/- 0.73 vs. 33.9 +/- 0.75 g/L), total cholesterol (2.04 +/- 0.30 vs. 2.45 +/- 0.42 mmol/L), and the highest concentrations of haptoglobin (0.67 vs. 0.24 +/- 0.03 g/L; positive acute phase protein) and globulins (37.2 vs. 32.3 +/- 1.4 g/L). Plasma bilirubin was highest in the cows (10.1 vs. 6.2 +/- 0.6 micromol/L) in the lowest PON quartile. Plasma PON was negatively correlated with haptoglobin (r = -0.39) and bilirubin (r = -0.42) and positively correlated with retinol binding protein (r = 0.54), albumin (r = 0.38), and cholesterol (r = 0.55) fractions. A total of 82.3% of cows in the lower quartile and no cows in the upper quartile experienced serious inflammation. Lower quartile cows produced 28.1 +/- 10.3 kg of milk/d; whereas upper quartile cows produced 38.3 +/- 7.7 kg of milk/d during the first 30 DIM. A reduction in the ability of the liver to cope with the increased metabolic demand near parturition in dairy cows can be diagnosed using changes in baseline plasma PON

Metabolic and biochemical changes in plasma of the periparturient rabbit does with different litter size.

The aim of this study was to investigate the metabolic and biochemical changes in plasma that occur in the reproductive rabbit doe close to the parturition, as well as if the number of offspring affects the metabolism and the health status of the doe. At −3, 4 and 12 days from parturition (–D3, D4, and D12, respectively) nine rabbit does at their third parity from a commercial hybrid line (HYPLUS PS 19) selected for high prolificacy were weighted and blood was collected for a wide inflammometabolic profile. According to the number of offspring the does were retrospectively divided in two groups: high litter size group (HI; n=5) and low litter size group (LO; n=4). BW was higher (P<0.01) at –D3 and had the lowest values at D4. At D12, the BW was lower (P<0.05) in LO compared with HI. Several metabolites significantly changed from dry to lactation period. Glucose and cholesterol had the lowest levels at –D3; non-esterified fatty acid (NEFA) and aspartate aminotransferase had the highest values before parturition (P<0.05); creatinine and β-hydroxybutyrate (BHBA) were higher at –D3 with respect to D4 (P<0.05). The lowest value of paraoxonase was observed in does at –D3 (P<0.05), whereas at this time ceruloplasmin and total bilirubin had the highest concentration (P<0.05). The differences for blood profile parameters between does grouped according to litter size were mainly evident before parturition (–D3). In particular, BHBA, NEFA and total bilirubin had higher concentrations (P<0.05) in HI v. LO group, whereas albumin and PON were lower in HI group (P<0.01). After parturition there were no significant differences for the metabolic parameters between the two groups. The results show that for reproductive rabbit doe the last days of gestation are very stressful from a metabolic and inflammatory point of view. The genetic selection of does for higher litter size has increased their ability to mobilize body reserves in order to guarantee the nutrients to a high number of kits. This exposes them to a more severe metabolic and inflammatory challenge during the transition period. Consequently, feeding and managerial strategies for high prolificacy periparturient rabbit does should be revised

Effect of dietary starch level and high rumen-undegradable protein on endocrine-metabolic status, milk yield, and milk composition in dairy cows during early and late lactation

Diet composition defines the amount and type of nutrients absorbed by dairy cows. Endocrine-metabolic interactions can influence these parameters, and so nutrient availability for the mammary gland can significantly vary and affect milk yield and its composition. Six dairy cows in early and then late lactation received, for 28 d in a changeover design, 2 diets designed to provide, within the same stage of lactation, similar amounts of rumen fermentable material but either high starch plus sugar (HS) content or low starch plus sugar content (LS). All diets had similar dietary crude protein and calculated supply of essential amino acids. Dry matter intake within each stage of lactation was similar between groups. Milk yield was similar between groups in early lactation, whereas a higher milk yield was observed in late lactation when feeding HS. At the metabolic level, the main difference observed between the diets in both stages of lactation was lower blood glucose in cows fed LS. The lower glucose availability during consumption of LS caused substantial modifications in the circulating and postprandial pattern of metabolic hormones. Feeding LS versus HS resulted in an increase in the ratio of bovine somatotropin to insulin. This increased mobilization of lipid reserves resulted in higher blood concentrations of nonesterified fatty acids and β-hydroxybutyrate, which contributed to the higher milk fat content in both stages of lactation in the LS group. This greater recourse to body fat stores was confirmed by the greater loss of body weight during early lactation and the slower recovery of body weight in late lactation in cows fed LS. The lower insulin to glucagon ratio observed in cows fed LS in early and late lactation likely caused an increase in hepatic uptake and catabolism of amino acids, as confirmed by the higher blood urea concentrations. Despite the higher catabolism of amino acids in LS in early lactation, similar milk protein output was observed for both diets, suggesting similar availability of amino acids for peripheral tissue and mammary gland. The latter could be the result of sparing of amino acids at the gut level due to starch that escaped from the rumen, and to the balanced amino acid profile of digestible protein. This last aspect appears worthy of further research, with the aim to enhance the efficiency of protein metabolism of dairy cows, reducing environmental nitrogen pollution without affecting milk yield potential

Effect of litter size on prepartum metabolic and amino acidic profile in rabbit does.

The use of modern prolific lines of rabbit does in intensive production systems leads to an increase in productivity but also causes a rise in several problems related to the does' health status. Hence, the aim of this study was to investigate the effect of the litter size on the metabolic, inflammatory and plasma amino acid profile in rabbit does. The blood of 30 pregnant does was sampled on the 27th day of pregnancy. The does were retrospectively grouped according to the number of offspring into a high litter size group (HI, does with ≥ 12 kits; n = 16) and a low litter size group (LO, does with ≤ 11 kits; n = 14). Data were subjected to Pearson's correlation analysis. Further, data were analysed in agreement to a completely randomized design in which the main tested effect was litter size. The linear or quadratic trends of litter size on parameters of interests were post hoc compared by using orthogonal contrasts. In addition, compared with the LO group, the HI group had lower levels of glucose (-5%; P < 0.01), zinc (-19%; P < 0.05), albumin (-6%; P < 0.05) and total cholesterol (-13%; P < 0.07), but the total bilirubin level was higher in the HI group (+14%; P < 0.05). Regarding the plasma amino acids, the HI group had lower concentrations of threonine (-15%), glycine (-16%), lysine (-16%) and tryptophan (-26%) and a higher level of glutamic acid (+43%; P < 0.05) compared with the LO group. The exclusively ketogenic amount of amino acids was lower (P < 0.06) in the HI (55.8 mg/100 ml) does compared with the LO does (56.8 mg/100 ml). These results show that a few days before delivery, rabbit does that gave birth to a higher number of offspring had a metabolic profile and an inflammatory status that was less favourable with respect to does who gave birth to a lower number of offspring. Moreover, the plasma amino acid profile points out that there was an enhanced catabolic condition in the rabbit does with a high number of gestated foetuses; it was likely related to the greater energy demand needed to support the pregnancy and an early inflammatory response

Dietary energy level affects adipose depot mass but does not impair in vitro subcutaneous adipose tissue response to short-term insulin and tumor necrosis factor-α challenge in nonlactating, nonpregnant Holstein cows.

We assessed effects of overfeeding energy to nonlactating and nonpregnant Holstein cows during a length of time similar to a typical dry period on body lipid storage and the abundance of genes related to insulin signaling, inflammation, and ubiquitination in subcutaneous adipose tissue (SAT) in vitro challenged with insulin and recombinant bovine tumor necrosis factor-α. Fourteen cows were randomly assigned to either a high-energy (OVE; net energy for lactation = 1.60 Mcal/kg of dry matter; n = 7) or control (CON; net energy for lactation = 1.30 Mcal/kg of dry matter; n = 7) diet for 6 wk. Immediately after slaughter, liver, kidneys, and mammary gland were separated and weighed. The adipose tissue mass in the omental, mesenteric, and perirenal depots was dissected and weighed. Subcutaneous adipose tissue was collected from the tail-head region and was used as follows: control, bovine insulin (INS) at 1 µmol/L, tumor necrosis factor-α at 5 ng/mL (TNF), and their combination. Despite a lack of difference in final body condition score, OVE cows had greater energy intake and were heavier than CON cows. Furthermore, overfeeding led to greater mass of mesenteric and perirenal adipose, liver, and mammary gland. Overall, SAT incubated with INS had an upregulation of insulin receptor (INSR), interleukin-10 (IL10), small ubiquitin-like modifier 3 (SUMO3), and ubiquitin conjugating enzyme E2I (UBC9), whereas TNF upregulated peroxisome proliferator-activated receptor gamma (PPARG), diacylglycerol O-acyltransferase 2 (DGAT2), interleukin-6 (IL6), nuclear factor kappa B subunit 1 (NFKB1), small ubiquitin-like modifier 2 (SUMO2), and UBC9. Regardless of in vitro treatment, feeding OVE upregulated PPARG, fatty acid synthase (FASN), and insulin induced gene 1 (INSIG1). Abundance of PPARG was greater in SAT of OVE cows cultured individually with INS and TNF. The interaction between diet and in vitro treatment revealed that sterol regulatory element binding transcription factor 1 (SREBF1) had greater abundance in SAT from the CON group in response to culture with INS, whereas SAT from OVE cows had greater SREBF1 abundance in response to culture with TNF. The mRNA abundance of IL6 and NFKB1 was greater in response to TNF treatment and overall in CON cows. Furthermore, SAT from these cows had greater IL10 abundance when cultured with INS and TNF. Overall, data highlighted that overfeeding energy increases adipose tissue mass in part by stimulating transcription of key genes associated with insulin signaling, adipogenesis, and lipogenesis. Because SAT thickness or mass was not measured, the lack of effect of overfeeding on body condition score limits its use to predict overall body lipid storage. An overt inflammatory response in SAT after a 6-wk period of over-consumption of energy could not be discerned

Immunometabolic status and productive performance differences between periparturient Simmental and Holstein dairy cows in response to pegbovigrastim

In the present study, we aimed to investigate the side effects of pegbovigrastim, injected approximately 7 d before parturition and on the day of calving, on a panel of plasma biomarkers to evaluate energy, inflammatory, oxidative, and liver function status. We also addressed treatment responses in different breeds during the transition period. Holstein and Simmental cows were randomly assigned into 2 groups based on expected calving date and according to parity: the treated group (PEG; 14 Holstein and 12 Simmental cows) received pegylated recombinant bovine granulocyte colony stimulating factor (pegbovigrastim, Imrestor; Elanco Animal Health, Greenfield, IN), and the control group (CTR; 14 Holstein and 14 Simmental cows) received saline solution. The PEG or CTR treatments were administered via subcutaneous injection in the scapular region at approximately 7 d (mean 7.80 ± 5.50 d) before expected parturition and within 24 h after calving. Blood samples were collected at -21, -7 (before injection), 1, 3, and 28 d relative to calving. Milk production was recorded at 7, 15, 21, 30, and 42 d. A mixed model with repeated measures was fitted to the normalized data using Proc MIXED of SAS (SAS Institute Inc., Cary, NC). Simmental PEG cows showed higher plasma protein concentrations at 1 and 3 d after calving compared with Simmental CTR and Holstein PEG cows, whereas no differences were detected between Holstein PEG and CTR cows. Albumin was greater at 1 d in Simmental PEG compared with Simmental CTR cows. In contrast, γ-glutamyl transferase was higher overall (across breed) in PEG than in CTR. The PEG group had higher values throughout the postcalving period compared with CTR. Cows treated with pegbovigrastim had also higher alkaline phosphatase (ALP) activity at 1 and 3 d after calving. The Holstein PEG group had higher ALP activity at 3 d compared with the Holstein CTR and Simmental PEG groups, and higher ALP at 1 d compared with the Simmental CTR group. The PEG group had higher levels of IL-6 at 3 and 28 d but higher IL-1β only at 28 d after calving compared with the CTR group. Overall, Holstein cows were characterized by a greater response in the production of inflammation biomarkers (cytokines, haptoglobin, and ceruloplasmin). In addition, PEG cows had higher values of zinc at 1 and 3 d after calving compared with CTR cows. The response observed in plasma biomarkers for energy metabolism and liver functionality after pegbovigrastim treatment in Simmental and Holstein cows was not different from that in control cows. However, our data shed light on the different metabolic adaptations during the transition period between Simmental and Holstein cows, characterized by different energy, inflammatory, and oxidative pattern responses. For the first time, we have highlighted the effect of pegbovigrastim in maintaining stable cytokine levels during the first month after parturition, reflecting greater regulation of neutrophil recruitment, trafficking, and maturation during the inflammatory response. These results provide evidence of the immunomodulatory action of pegbovigrastim around parturition, when dairy cows are highly immunosuppressed. At the same time, these data demonstrate that increasing release of cytokines after parturition is not linked to exacerbation of a systemic inflammation evaluated based on haptoglobin and ceruloplasmin levels

A mycotoxin-deactivating feed additive counteracts the adverse effects of regular levels of Fusarium mycotoxins in dairy cows.

Little is known about the effects of commonly found levels of Fusarium mycotoxins on the performance, metabolism, and immunity of dairy cattle. We investigated the effects of regular contamination levels, meaning contamination levels that can be commonly detected in dairy feeds, of deoxynivalenol (DON) and fumonisins (FB) in total mixed ration (TMR) on the performance, diet digestibility, milk quality, and plasma liver enzymes in dairy cows. This trial examined 12 lactating Holstein dairy cows using a 3-period × 3-treatment Latin square design. The experimental period was 21 d of mycotoxin exposure followed by 14 d of washout. During treatment periods, cows received one of 3 diets: (1) CTR (control) diet of TMR contaminated with 340.5 µg of DON/kg of dry matter (DM) and 127.9 µg FB/kg of DM; (2) MTX diet of TMR contaminated with Fusarium mycotoxins at levels higher than CTR but below US and European Union guidelines (i.e., 733.0 µg of DON/kg of DM and 994.4 µg of FB/kg of DM); or (3) MDP diet, which was MTX diet supplemented with a mycotoxin deactivator product (i.e., 897.3 µg of DON/kg of DM and 1,247.1 µg of FB/kg of DM; Mycofix, 35 g/animal per day). During washout, all animals were fed the same CTR diet. Body weight, body condition score, DM intake, dietary nutrient digestibility, milk production, milk composition and rennet coagulation properties, somatic cell count, blood serum chemistry, hematology, serum immunoglobulin concentrations, and expression of multiple genes in circulating leucocytes were measured. Milk production was significantly greater in the CTR group (37.73 kg/d) than in the MTX (36.39 kg/d) and the MDP (36.55 kg/d) groups. Curd firmness and curd firming time were negatively affected by the MTX diet compared with the other 2 diets. Furthermore, DM and neutral detergent fiber digestibility were lower after the MTX diet than after the CTR diet (67.3 vs. 71.0% and 42.8 vs. 52.3%). The MDP diet had the highest digestibility coefficients for DM (72.4%) and neutral detergent fiber (53.6%) compared with the other 2 diets. The activities of plasma liver transaminases were higher after the MTX diet than after the CTR and MDP diets. Compared with the CTR diet, the MTX diet led to slightly lower expression of genes related to immune and inflammatory functions, indicating that Fusarium mycotoxins had an immunosuppressive effect. Our results indicated that feed contaminated with regular levels of Fusarium mycotoxins adversely affected the performance, milk quality, diet digestibility, metabolic variables, and immunity of dairy cows, and that supplementation with mycotoxin deactivator product counteracted most of these negative effects

Grain challenge affects systemic and hepatic molecular biomarkers of inflammation, stress, and metabolic responses to a greater extent in Holstein than Jersey cows

Long-term feeding of high-grain diets to dairy cows often results in systemic inflammation characterized by alterations in acute-phase proteins and other biomarkers, both in plasma and immune-responsive tissues like the liver. The molecular and systemic changes that characterize an acute grain feeding challenge remain unclear. The current study involved 6 Holstein and 6 Jersey cows in a replicated 2 × 2 Latin square. Periods (10 d) were divided into 4 stages (S): S1, d 1 to 3, served as baseline with total mixed ration (TMR) ad libitum; S2, d 4, served as restricted feeding, with cows offered 50% of the average daily intake observed in S1; S3, d 5, a grain challenge was performed, in which cows were fed a TMR ad libitum without (CON) or with an additional pellet wheat-barley (1:1; HIG) at 20% of dry matter intake top-dressed onto the TMR; S4, d 6 to 10, served as recovery during which cows were allowed ad libitum access to the TMR. Among the 28 biomarkers analyzed in blood 12 h after grain challenge on d 5, the concentrations of fatty acids and bilirubin increased in HIG Holstein but not Jersey cows. In Holsteins, feeding HIG also increased total protein and albumin while decreasing ceruloplasmin, myeloperoxidase, and alkaline phosphatase concentrations. At the molecular level, hepatic genes associated with inflammation (IL1B, IL6, TNF, TLR4, MYD88, and NFKB1) were upregulated in Holstein cows fed HIG versus CON. Despite such response, expression of the acute-phase proteins SAA and HP in Holsteins fed HIG compared with CON was markedly downregulated. In Holsteins fed HIG versus CON, the marked downregulation of SCD, ELOVL6, and MTTP along with upregulated CPT1A, ACOX1, and APOA5 indicated alterations in fatty acid and lipoprotein metabolism during grain challenge. Genes related to ketogenesis (HMGCS2 and ACAT1) were upregulated in Jerseys, and gluconeogenic genes (PDK4 and PCK1) were upregulated in Holstein cows fed HIG, suggesting alterations in ketone body and glucose production. Expression of phosphorylated p70S6K1, RPS6, and 4EBP1 proteins, as well as total mechanistic target of rapamycin (mTOR) protein, decreased in Holsteins fed HIG, whereas phosphorylated mTOR and 4EBP1 proteins increased in Jerseys fed HIG. From a metabolic and inflammatory biomarker standpoint, data indicate that Jersey cows better tolerated the acute grain challenge. Alterations in mTOR signaling proteins in both Jerseys and Holsteins fed HIG suggest a potential role for exogenous AA in the hepatic adaptations to grain challenge. It remains to be determined if these acute responses to a grain challenge can elicit long-term liver dysfunction, which could negatively affect welfare of the cow

Increasing vegetable intakes: rationale and systematic review of published interventions

Purpose While the health benefits of a high fruit and vegetable consumption are well known and considerable work has attempted to improve intakes, increasing evidence also recognises a distinction between fruit and vegetables, both in their impacts on health and in consumption patterns. Increasing work suggests health benefits from a high consumption specifically of vegetables, yet intakes remain low, and barriers to increasing intakes are prevalent making intervention difficult. A systematic review was undertaken to identify from the published literature all studies reporting an intervention to increase intakes of vegetables as a distinct food group. Methods Databases—PubMed, PsychInfo and Medline—were searched over all years of records until April 2015 using pre-specified terms. Results Our searches identified 77 studies, detailing 140 interventions, of which 133 (81 %) interventions were conducted in children. Interventions aimed to use or change hedonic factors, such as taste, liking and familiarity (n = 72), use or change environmental factors (n = 39), use or change cognitive factors (n = 19), or a combination of strategies (n = 10). Increased vegetable acceptance, selection and/or consumption were reported to some degree in 116 (83 %) interventions, but the majority of effects seem small and inconsistent. Conclusions Greater percent success is currently found from environmental, educational and multi-component interventions, but publication bias is likely, and long-term effects and cost-effectiveness are rarely considered. A focus on long-term benefits and sustained behaviour change is required. Certain population groups are also noticeably absent from the current list of tried interventions