Dataset Information

Integrative analyses of hepatic differentially expressed genes and blood biomarkers during the peripartal period between dairy cows overfed or restricted-fed energy prepartum.

ABSTRACT: Using published dairy cattle liver transcriptomics dataset along with novel blood biomarkers of liver function, metabolism, and inflammation we have attempted an integrative systems biology approach applying the classical functional enrichment analysis using DAVID, a newly-developed Dynamic Impact Approach (DIA), and an upstream gene network analysis using Ingenuity Pathway Analysis (IPA). Transcriptome data was generated from experiments evaluating the impact of prepartal plane of energy intake [overfed (OF) or restricted (RE)] on liver of dairy cows during the peripartal period. Blood biomarkers uncovered that RE vs. OF led to greater prepartal liver distress accompanied by a low-grade inflammation and larger proteolysis (i.e., higher haptoglobin, bilirubin, and creatinine). Post-partum the greater bilirubinaemia and lipid accumulation in OF vs. RE indicated a large degree of liver distress. The re-analysis of microarray data revealed that expression of >4,000 genes was affected by diet × time. The bioinformatics analysis indicated that RE vs. OF cows had a liver with a greater lipid and amino acid catabolic capacity both pre- and post-partum while OF vs. RE cows had a greater activation of pathways/functions related to triglyceride synthesis. Furthermore, RE vs. OF cows had a larger (or higher capacity to cope with) ER stress likely associated with greater protein synthesis/processing, and a higher activation of inflammatory-related functions. Liver in OF vs. RE cows had a larger cell proliferation and cell-to-cell communication likely as a response to the greater lipid accumulation. Analysis of upstream regulators indicated a pivotal role of several lipid-related transcription factors (e.g., PPARs, SREBPs, and NFE2L2) in priming the liver of RE cows to better face the early postpartal metabolic and inflammatory challenges. An all-encompassing dynamic model was proposed based on the findings.

SUBMITTER: Shahzad K

PROVIDER: S-EPMC4051754 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Integrative analyses of hepatic differentially expressed genes and blood biomarkers during the peripartal period between dairy cows overfed or restricted-fed energy prepartum.

Shahzad Khuram K Bionaz Massimo M Trevisi Erminio E Bertoni Giuseppe G Rodriguez-Zas Sandra L SL Loor Juan J JJ

PloS one 20140610 6

Using published dairy cattle liver transcriptomics dataset along with novel blood biomarkers of liver function, metabolism, and inflammation we have attempted an integrative systems biology approach applying the classical functional enrichment analysis using DAVID, a newly-developed Dynamic Impact Approach (DIA), and an upstream gene network analysis using Ingenuity Pathway Analysis (IPA). Transcriptome data was generated from experiments evaluating the impact of prepartal plane of energy intake ...[more]

PMID: 24914544

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Project description:BackgroundThe aim of the study was to investigate the effect of energy overfeeding during the dry period on adipose tissue transcriptome profiles during the periparturient period in dairy cows.MethodsFourteen primiparous Holstein cows from a larger cohort receiving a higher-energy diet (1.62 Mcal of net energy for lactation/kg of dry matter; 15% crude protein) for ad libitum intake to supply 150% (OVR) or 100% (CTR) of energy requirements from dry off until parturition were used. After calving, all cows received the same lactation diet. Subcutaneous adipose tissue (SAT) biopsies were collected at - 14, 1, and 14 d from parturition (d) and used for transcriptome profiling using a bovine oligonucleotide microarray. Data mining of differentially expressed genes (DEG) between treatments and due to sampling time was performed using the Dynamic Impact Approach (DIA) and Ingenuity Pathway Analysis (IPA).ResultsThere was a strong effect of over-feeding energy on DEG with 2434 (False discovery rate-corrected P < 0.05) between OVR and CTR at - 14 d, and only 340 and 538 at 1 and 14 d. The most-impacted and activated pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database that were highlighted by DIA analysis at - 14 d in OVR vs. CTR included 9 associated with carbohydrate metabolism, with 'Pyruvate metabolism', 'Glycolysis/gluconeogenesis', and 'Pentose phosphate pathway' among the most-activated. Not surprisingly, OVR led to marked activation of lipid metabolism (e.g. 'Fatty acid biosynthesis' and 'Glycerolipid metabolism'). Unexpected metabolic pathways that were activated at - 14 d in OVR included several related to metabolism of amino acids (e.g. branched chain) and of cofactors and vitamins (thiamin). Among endocrine and immune system pathways, at - 14 d OVR led to marked activation of 'PPAR signalling' and 'Antigen processing and presentation'. Among key pathways affected over time in OVR, a number were related to translation (e.g. mTOR signaling), endocrine/immune signaling (CXCR4 and IGF1), and lipid metabolism (oxidative phosphorylation) with greater activation in OVR vs. CTR specifically at - 14 d. Although statistical differences for several pathways in OVR vs. CTR nearly disappeared at 1 and 14 vs. - 14 d, despite the well-known catabolic state of adipose depots after calving, the bioinformatics analyses suggested important roles for a number of signaling mechanisms at - 14 vs. 14 than 1 vs. -14 d. This was particularly evident in cows fed to meet predicted energy requirements during the dry period (CTR).ConclusionsData underscored a strong activation by overfeeding energy of anabolic processes in the SAT exclusively prepartum. The study confirmed that higher-energy diets prepartum drive a transcriptional cascade of events orchestrated in part by the activation of PPARγ that regulate preadipocyte differentiation and lipid storage in SAT. Novel aspects of SAT biology to energy overfeeding or change in physiologic state also were uncovered, including the role of amino acid metabolism, mTOR signaling, and the immune system.

Project description:Periparturient diseases of dairy cows are caused by disproportionate energy metabolism, mineral imbalance, and perturbed immune function. The aim of the present study was to characterize metabolism, innate immune endometrial gene expression, and uterine microbial populations of transition animals receiving normal or restricted energy diets. Pregnant multiparous Holstein cows (n = 14) were randomly assigned to one of the two dietary treatments from 20 d prepartum until 35 d postpartum (DPP). One group was fed a diet providing 100% energy requirements (NE), whereas the other received an energy-restricted diet providing 80% energy requirements (RE). Feed intake, milk yield, body weight, body condition score, temperature, respiratory, and pulse rate were recorded. After calving, blood was collected weekly to analyze nonesterified fatty acids (NEFAs), β-hydroxybutyrate (BHB), and total cholesterol (TC). Endometrial cytobrushes were collected for gene expression analysis of inflammatory markers, microbial populations determination, and cytological evaluation. The restricted energy diet did not alter feed intake or milk yield but changed energy balance and metabolites levels (P < 0.05). In fact, RE animals had high NEFA and BHB levels, and low TC concentrations (P < 0.05). Moreover, RE animals had upregulated gene expression of serum amyloid A3 (SAA3) at 35 DPP (P < 0.05) and CXC chemokine receptor 2 (CXCR2) at 14 DPP (P < 0.01). Interleukin (IL) 1 and IL8 genes were downregulated 14 DPP but upregulated 35 DPP in RE animals, whereas IL6 and lipopolysaccharide-binding protein (LBP) genes were upregulated at 14 DPP (P ≤ 0.05). The most abundant phyla in RE animals (n = 3) were Bacteroidetes and Fusobacteria, whereas Proteobacteria was the least abundant at both 14 and 35 DPP. In conclusion, it can be speculated that energy balance is one of the main drivers for uterine inflammation by affecting metabolism, immune function, and uterine microbiota. However, these findings should be validated in a larger sample size.

Project description:A transcriptomic approach was used to evaluate potential interactions between prepartum body condition score (BCS) and feeding management in the weeks before calving on hepatic metabolism during the transition period. Thirty-two mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to one of four treatment groups in a 2 × 2 factorial arrangement: two prepartum BCS categories [4.0 (thin, BCS4) and 5.0 (optimal, BCS5); based on a 10-point scale], and two levels of energy intake during the 3 wk preceding calving (75 and 125% of estimated requirements). Liver samples were obtained at -7, 7, and 28 d relative to parturition and subsequent RNA was hybridized to the Agilent 44K Bovine (V2) Microarray chip. The Dynamic Impact Approach was used for pathway analysis, and Ingenuity Pathway Analysis was used for gene network analysis. The greater number of differentially expressed genes in BCS4 cows in response to prepartum feed allowance indicated that these animals were more responsive to prepartum nutrition management than optimally-conditioned cows. However, independent of prepartum BCS, pathway analysis revealed that prepartal feeding level had a marked effect on carbohydrate, amino acid, lipid, and glycan metabolism. Altered carbohydrate and amino acid metabolism indicated a greater and more prolonged negative energy balance post-calving in BCS5 cows overfed prepartum. This was indicated by opposite effects of pre-calving feeding in in BCS4 compared with BCS5 cows in amino acid, vitamin, and co-factor metabolism. The prepartum feed restriction ameliorated the metabolic adaptation to the new lactation in BCS5 cows, while detrimentally affecting BCS4 cows, which seemed to adapt better when overfed. Moreover, alterations in the glycosaminoglycans synthesis pathway support this idea, indicating better hepatic health status in feed-restricted BCS5 cows and overfed BCS4 animals. IPA network analysis indicated liver damage in feed-restricted thin cows, likely due to metabolic overload. Overall, the data indicate that overfeeding in late-pregnancy should be limited to underconditioned animals, while cow with optimal degree of body condition should be maintained on an energy restricted diet.

Project description:BackgroundOverconditioned dairy cows are susceptible to excessive lipolysis and increased insulin resistance during the transition period. The associations among body fat reserve, insulin resistance, and lipolysis in adipose tissues (AT) remain to be elucidated. Therefore, this study aimed to investigate whether excessive fat reserves influence the insulin signaling pathway in AT postpartum.ResultsTwenty multiparous dairy cows were selected and assigned to one of two groups, according to prepartum body condition score (BCS): Control group (BCS = 3.0-3.5; n = 10) and Overconditioned group (BCS ≥ 4.0; n = 10). Blood samples were collected on days -14, -7, -4, -2, -1, 0, 1, 2, 4, 7, and 14 relative to parturition. Subcutaneous AT were collected on day 2 following parturition for quantitative real-time polymerase chain reaction and western blot analyses. No differences were observed between the two groups in serum glucose, non-esterified fatty acids, β-hydroxybutyric acid, tumor necrosis factor (TNF) α, insulin, or leptin concentrations during the experimental period. Compared with the control cows, the overconditioned cows had lower serum triglyceride levels and higher adiponectin concentrations. In the AT postpartum, insulin receptor mRNA and protein levels were lower in the overconditioned cows than in the control cows, and no differences were found in glucose transporter 4 mRNA. Compared with the control cows, the overconditioned cows had lower mRNA levels of TNFα and higher mRNA levels of peroxisome proliferator-activated receptor gamma (PPARγ) in AT postpartum. The phosphorylated protein kinase B (AKT) content and phosphorylation rate of AKT were increased in the overconditioned cows compared with the control cows, which suggested that the downstream insulin signaling in AT was affected.ConclusionsIn the present study, transition dairy cows with higher BCS did not show more fat mobilization. The changes of insulin signaling pathway in AT postpartum of overconditioned cows may be partly related to the expression of PPARγ and TNFα, and the secretion of adiponectin.

Dataset Information

Integrative analyses of hepatic differentially expressed genes and blood biomarkers during the peripartal period between dairy cows overfed or restricted-fed energy prepartum.

Publications

Integrative analyses of hepatic differentially expressed genes and blood biomarkers during the peripartal period between dairy cows overfed or restricted-fed energy prepartum.

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