Dairy cows affected by ketosis show alterations in innate immunity and lipid and carbohydrate metabolism during the dry off period and postpartum

Zhang, Guanshi; Hailemariam, Dagnachew; Dervishi, Elda; Goldansaz, Seyed Ali; Deng, Qilan; Dunn, Suzanna M.; Ametaj, Burim N.

doi:10.1016/j.rvsc.2016.06.012

Cited by 66 publications

(75 citation statements)

References 38 publications

(29 reference statements)

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“…However, high levels of NEFAs, a pathological factor of ketosis, induce lipotoxicity and can impair cellular metabolic function and activate inflammatory pathways [17]. Many diseases that occur during the perinatal period, including mastitis and metritis, are related to elevated concentrations of NEFAs in dairy cows [7,8,18]. In the present study, we found that the blood concentrations of the proinflammatory cytokines IL-1β, IL-6, and TNF-α were significantly increased in ketotic cows and had a positive relationship with the concentrations of NEFAs.…”

Section: Discussionmentioning

confidence: 99%

“…Clinical data have indicated that high levels of NEFAs are related to the inflammatory response in the progression of some diseases, such as mastitis and metritis, in dairy cows [6,7]. Ketotic cows have high blood concentrations of the inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and are believed to be more susceptible to mastitis and metritis during the transition period [8].…”

Section: Introductionmentioning

confidence: 99%

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Non-Esterified Fatty Acids Over-Activate the TLR2/4-NF-Κb Signaling Pathway to Increase Inflammatory Cytokine Synthesis in Neutrophils from Ketotic Cows

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Dairy cows with clinical ketosis display a negative energy balance and high blood concentrations of non-esterified fatty acids (NEFAs), the latter of which is an important pathological factor of ketosis in cows. The aims of this study were to investigate the inflammatory status of ketotic cows and to determine whether and through what underlying mechanism high levels of NEFAs induce an inflammatory response. Methods: Proinflammatory factors and the nuclear factor kappa B (NF-κB) signaling pathway were evaluated in neutrophils from clinical ketotic and control cows, using methods including western blotting, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay. In vitro, the effects of NEFAs on the NF-κB signaling pathway in cow neutrophils were also evaluated using the above experimental techniques. Results: Ketotic cows displayed low blood concentrations of glucose and high blood NEFA and β-hydroxybutyrate concentrations. Importantly, Toll-like receptor 2 (TLR2) and TLR4 expression and IκBα and NF-κB p65 phosphorylation levels in neutrophils (PMNs) were significantly higher in ketotic cows than in control cows, indicating over-activation of the TLR2/4-induced NF-κB inflammatory pathway in PMNs in ketotic cows. The blood concentrations of the inflammatory cytokines interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) were also significantly increased in ketotic cows. Interestingly, we found that NEFAs were positively correlated with proinflammatory cytokines. In vitro, after pharmacological inhibition of TLR2 and TLR4 expression in cow neutrophils, TLR2 and TLR4 expression was significantly decreased, and the phosphorylation level of NF-κB p65 was also reduced. Cow neutrophils were treated with different concentrations of NEFAs and pyrrolidine dithiocarbamate (PDTC; an NF-κB inhibitor). High concentrations of NEFAs (0.5 and 1 mM) significantly increased TLR2 and TLR4 expression, IκBα and NF-κB p65 phosphorylation levels, NF-κB p65 transcriptional activity, and IL-6, IL-1β, and TNF-α synthesis in cow neutrophils. The inhibition of NF-κB by PDTC suppressed the NEFA-induced synthesis of proinflammatory cytokines. Conclusions: High concentrations of NEFAs can over-activate the TLR2/4-mediated NF-κB signaling pathway to induce the over-production of proinflammatory cytokines, thereby increasing inflammation in cows with clinical ketosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Non-Esterified Fatty Acids Over-Activate the TLR2/4-NF-Κb Signaling Pathway to Increase Inflammatory Cytokine Synthesis in Neutrophils from Ketotic Cows

Zhang

et al. 2018

Cell Physiol Biochem

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“…In our study, we found lower levels of asparagine, lysine, glutamine, histidine, tryptophan, cysteine, and ornithine. Previously, the differential levels of amino acids in the blood of dairy cattle have been shown to correlate with ketosis 18,19,27 . One study looking at dairy cows with clinical ketosis found differential levels of 13 metabolites 19 .…”

Section: Discussionmentioning

confidence: 99%

Plasma metabolomic profiles differ at the time of artificial insemination based on pregnancy outcome, in Bos taurus beef heifers

Phillips

Read

Kriese-Anderson

et al. 2018

Sci Rep

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Infertility remains the most prevalent reason for cattle being removed from production environments. We utilized metabolomic profiling to identify metabolites in the blood plasma that may be useful in identifying infertile heifers at the time of artificial insemination (AI). Prior to AI, phenotypic parameters including body condition, weight, and reproductive organ measurements were collected. These were determined not effective at differentiating between fertile and infertile heifers. Analysis of the resulting metabolomic profiles revealed 15 metabolites at significantly different levels (T-test P ≤ 0.05), with seven metabolites having a greater than 2-fold difference (T-test P ≤ 0.05, fold change ≥2, ROC-AUC ≥ 0.80) between infertile and fertile heifers. We further characterized the utility of using the levels of these metabolites in the blood plasma to discriminate between fertile and infertile heifers. Finally, we investigated the potential role inflammation may play by comparing the expression of inflammatory cytokines in the white blood cells of infertile heifers to that of fertile heifers. We found significantly higher expression in infertile heifers of the proinflammatory markers tumor necrosis factor alpha (TNFα), interleukin 6 (IL6), and the C-X-C motif chemokine 5 (CXCL5). Our work offers potentially valuable information regarding the diagnosis of fertility problems in heifers undergoing AI.

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“…У роботі [11] наведено підвищення ІЛ-6 поряд з підвищенням концентрації гід-роксибутирату у хворих на кетоз корів . Нами не виявлено подібних змін.…”

Section: висновкиunclassified

Analysis of cytokins status in blood serum of cows with subclinical form of ketosis

Kibkalo¹

2017

Bìol. Tvarin

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Dairy cows affected by ketosis show alterations in innate immunity and lipid and carbohydrate metabolism during the dry off period and postpartum

Cited by 66 publications

References 38 publications

Non-Esterified Fatty Acids Over-Activate the TLR2/4-NF-Κb Signaling Pathway to Increase Inflammatory Cytokine Synthesis in Neutrophils from Ketotic Cows

Non-Esterified Fatty Acids Over-Activate the TLR2/4-NF-Κb Signaling Pathway to Increase Inflammatory Cytokine Synthesis in Neutrophils from Ketotic Cows

Plasma metabolomic profiles differ at the time of artificial insemination based on pregnancy outcome, in Bos taurus beef heifers

Analysis of cytokins status in blood serum of cows with subclinical form of ketosis

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