Dairy cows are highly susceptible after parturition to developing liver lipidosis and ketosis, which are costly diseases to farmers. A bovine microarray platform consisting of 13,257-annotated oligonucleotides was used to study hepatic gene networks underlying nutrition-induced ketosis. On day 5 postpartum, 14 Holstein cows were randomly assigned to ketosis-induction (n = 7) or control (n = 7) groups. Cows in the ketosis-induction group were fed at 50% of day 4 intake until they developed signs of clinical ketosis, and cows in the control group were fed ad libitum throughout the treatment period. Liver was biopsied at 10-14 (ketosis) or 14 days postpartum (controls). Feed restriction increased blood concentrations of nonesterified fatty acids and beta-hydroxybutyrate, but decreased glucose. Liver triacylglycerol concentration also increased. A total of 2,415 genes were altered by ketosis (false discovery rate = 0.05). Ingenuity Pathway Analysis revealed downregulation of genes associated with oxidative phosphorylation, protein ubiquitination, and ubiquinone biosynthesis with ketosis. Other molecular adaptations included upregulation of genes and nuclear receptors associated with cytokine signaling, fatty acid uptake/transport, and fatty acid oxidation. Genes downregulated during ketosis included several associated with cholesterol metabolism, growth hormone signaling, proton transport, and fatty acid desaturation. Feed restriction and ketosis resulted in previously unrecognized alterations in gene network expression underlying key cellular functions and discrete metabolic events. These responses might help explain well-documented physiological adaptations to reduced feed intake in early postpartum cows and, thus, provide molecular targets that might be useful in prevention and treatment of liver lipidosis and ketosis.

Long-term molecular adaptations in liver from high-producing dairy cows are virtually unknown. Liver from five Holstein cows was biopsied at -65, -30, -14, +1, +14, +28, and +49 days relative to parturition for transcript profiling using a microarray consisting of 7,872 annotated cattle cDNA inserts. More than 5,000 cDNA elements represented on the microarray were expressed in liver. From this set we identified 62 differentially expressed genes related to physiological state, with a false discovery rate threshold of P = 0.20. The dominant expression pattern consisted of upregulation from day -30 through day +1, followed by downregulation through day +28. There was a threefold decrease from day -65 through day +14 in expression of IGFBP3, GSTM5, and PDPK1. These genes mediate IGF-I transport, oxidative stress, and glucose homeostasis, respectively. IGFBP3, EIF4B, and GSTM5 mRNA levels were positively correlated with blood serum total protein. Correlation analysis showed positive associations between serum nonesterified fatty acids and mRNA expression for SAA1, CPT1A, ACADVL, and TFAP2A. Transcript levels of ACSL1, PPARA, and TFAP2A were positively correlated with serum beta-hydroxybutyrate. Expression patterns for certain genes (e.g., IGFBP3, HNF4A, GPAM) revealed adaptations commencing well ahead of parturition, suggesting they are regulated by factors other than periparturient hormonal environment. Results provide evidence that hepatic inflammatory responses occurring near parturition initiate or augment adipose catabolism. In this context, cytokines, acute-phase proteins, and serum nonesterified fatty acids are key players in periparturient cow metabolism. We propose a model for integrating gene expression, metabolite, and liver composition data to explain physiological events in placenta, adipose, and liver during the periparturient period.

Liver metabolism and health in dairy cows during the periparturient period are affected by plane of nutrition prepartum. Long-term adaptations in hepatic gene expression are important for complete understanding of liver function. We examined temporal gene expression profiles during the dry period and early lactation in liver of Holstein cows fed moderate dietary energy ad libitum or restricted during the entire dry period using a microarray consisting of 7,872 annotated cattle cDNA inserts and quantitative RT-PCR. We identified 85 genes with expression patterns that were affected by level of energy intake prepartum over time. Restricted energy intake prepartum resulted in more pronounced upregulation of genes with key functions in hepatic fatty acid oxidation (CPT1A, ADIPOR2), gluconeogenesis (PC), and cholesterol synthesis (SC4MOL). Ad libitum feeding upregulated a number of genes associated with liver triacylglycerol synthesis (DGAT1) and proinflammatory cytokines (TNFAIP3). Genomic responses to ad libitum feeding were accompanied by increased incorporation of palmitate to esterified products in vitro and increased liver triacylglycerol concentration in vivo. Overall, gene expression profiles due to plane of nutrition prepartum partly explained differences in rates of liver palmitate metabolism, blood serum metabolite concentrations, and liver tissue triacylglycerol concentration. Our data show that moderate overfeeding of energy in the dry period, in the absence of obesity, results in transcriptional changes predisposing cows to fatty liver and perhaps compromising overall liver health during the periparturient period. In this context, controlled energy intake may confer an advantage to the cow by triggering hepatic molecular adaptations well ahead of parturition.

BackgroundTicks attach to and penetrate their hosts’ skin and inactivate multiple components of host responses in order to acquire a blood meal. Infestation loads with the cattle tick, Rhipicephalus microplus, are heritable: some breeds carry high loads of reproductively successful ticks, whereas in others, few ticks feed and reproduce efficiently.MethodsIn order to elucidate the mechanisms that result in the different outcomes of infestations with cattle ticks, we examined global gene expression and inflammation induced by tick bites in skins from one resistant and one susceptible breed of cattle that underwent primary infestations with larvae and nymphs of R. microplus. We also examined the expression profiles of genes encoding secreted tick proteins that mediate parasitism in larvae and nymphs feeding on these breeds.ResultsFunctional analyses of differentially expressed genes in the skin suggest that allergic contact-like dermatitis develops with ensuing production of IL-6, CXCL-8 and CCL-2 and is sustained by HMGB1, ISG15 and PKR, leading to expression of pro-inflammatory chemokines and cytokines that recruit granulocytes and T lymphocytes. Importantly, this response is delayed in susceptible hosts. Histopathological analyses of infested skins showed inflammatory reactions surrounding tick cement cones that enable attachment in both breeds, but in genetically tick-resistant bovines they destabilized the cone. The transcription data provided insights into tick-mediated activation of basophils, which have previously been shown to be a key to host resistance in model systems. Skin from tick-susceptible bovines expressed more transcripts encoding enzymes that detoxify tissues. Interestingly, these enzymes also produce volatile odoriferous compounds and, accordingly, skin rubbings from tick-susceptible bovines attracted significantly more tick larvae than rubbings from resistant hosts. Moreover, transcripts encoding secreted modulatory molecules by the tick were significantly more abundant in larval and in nymphal salivary glands from ticks feeding on susceptible bovines.ConclusionsCompared with tick-susceptible hosts, genes encoding enzymes producing volatile compounds exhibit significantly lower expression in resistant hosts, which may render them less attractive to larvae; resistant hosts expose ticks to an earlier inflammatory response, which in ticks is associated with significantly lower expression of genes encoding salivary proteins that suppress host immunity, inflammation and coagulation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1945-z) contains supplementary material, which is available to authorized users.