Relationships between metabolic profiles and gene expression in liver and leukocytes of dairy cows in early lactation

Wathes, D C; Cheng, Zhangrui; Salavati, Mazdak; Buggiotti, Laura; Takeda, Hitoshi; Tang, Lanhua; Becker, Frank; Ingvartsen, Klaus Lønne; Ferris, C.P.; Hostens, Miel; Crowe, M.A.

doi:10.3168/jds.2020-19165

Cited by 27 publications

(23 citation statements)

References 104 publications

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“…RNA-seq data and eQTL mapping. We used RNA-seq data produced by the GplusE consortium (http://www.gpluse.eu/; EBI ArrayExpress: E-MTAB-9348 and 9871) [100]. RNA-seq libraries were constructed using Illumina TruSeq Stranded Total RNA Library Prep Ribo-Zero Gold kit (Illumina, San Diego, CA) and sequenced on Illumina NextSeq 500 sequencer with 75-nucleotide single-end reads to reach average 32 million reads per sample.…”

Section: Eqtl Mapping and Summary Data-based Mendelian Randomization Analysismentioning

confidence: 99%

A 12 kb multi-allelic copy number variation encompassing a GC gene enhancer is associated with mastitis resistance in dairy cattle

et al. 2021

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Clinical mastitis (CM) is an inflammatory disease occurring in the mammary glands of lactating cows. CM is under genetic control, and a prominent CM resistance QTL located on chromosome 6 was reported in various dairy cattle breeds. Nevertheless, the biological mechanism underpinning this QTL has been lacking. Herein, we mapped, fine-mapped, and discovered the putative causal variant underlying this CM resistance QTL in the Dutch dairy cattle population. We identified a ~12 kb multi-allelic copy number variant (CNV), that is in perfect linkage disequilibrium with a lead SNP, as a promising candidate variant. By implementing a fine-mapping and through expression QTL mapping, we showed that the group-specific component gene (GC), a gene encoding a vitamin D binding protein, is an excellent candidate causal gene for the QTL. The multiplicated alleles are associated with increased GC expression and low CM resistance. Ample evidence from functional genomics data supports the presence of an enhancer within this CNV, which would exert cis-regulatory effect on GC. We observed that strong positive selection swept the region near the CNV, and haplotypes associated with the multiplicated allele were strongly selected for. Moreover, the multiplicated allele showed pleiotropic effects for increased milk yield and reduced fertility, hinting that a shared underlying biology for these effects may revolve around the vitamin D pathway. These findings together suggest a putative causal variant of a CM resistance QTL, where a cis-regulatory element located within a CNV can alter gene expression and affect multiple economically important traits.

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Section: Eqtl Mapping and Summary Data-based Mendelian Randomization Analysismentioning

confidence: 99%

A 12 kb multi-allelic copy number variation encompassing a GC gene enhancer is associated with mastitis resistance in dairy cattle

et al. 2021

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“…Although TNF and HSP70 have important roles in the inflammatory response (Beutler and Cerami, 1989;Jacquier-Sarlin et al, 1994), their mRNA expressions were not affected by our experimental treatments. Gene expression of HSP70 was shown to be upregulated in leukocytes of early-lactating cows with an unfavorable metabolic profile (Wathes et al, 2021). As all cows enrolled in the present study were in healthy condition and had a low milk SCC before dryoff, the presented immune parameters were expressed at a basal level.…”

Section: Effect Of Dietary Treatments Feed Restriction and Dry-off On...mentioning

confidence: 76%

Effect of different dietary regimens at dry-off on performance, metabolism, and immune system in dairy cows

Jermann

Fritsche

Wagner

et al. 2022

Journal of Dairy Science

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Concentrate withdrawal and feed restriction are commonly used to reduce milk production and to facilitate dry-off, but may impair immune function in dairy cows. We investigated the effect of feed rations providing different amounts of nutrients in combination with feed restriction on performance, endocrine, and metabolic responses, as well as on leukocyte function before and after abrupt dry-off. Forty-three cows were studied from d 12 before until d 6 after dry-off (56 d before scheduled calving). Cows were fed experimental concentrates rich in crude protein (nitrogenic, n = 14), glucogenic precursors (glucogenic, n = 14), or lipids (lipogenic, n = 15). On d 3 before dry-off, total feed allowance was restricted to 50% in half of the animals of each dietary group, whereas feed allowance remained unchanged in the other animals. Performance parameters (milk yield, milk composition, and dry matter intake) were recorded, and daily blood and milk samples were taken and analyzed for various metabolic and endocrine parameters. Additionally, activity and mRNA abundance of several genes in leukocytes were measured at selected time points before and after feed restriction and dryoff, respectively. Feed restriction immediately resulted in a negative energy balance and decreased milk production. Concomitantly, concentrations of nonesterified fatty acids increased, whereas insulin, insulin-like growth factor-1, and glucagon decreased. After dry-off, energy balance turned positive and plasma nonesterified fatty acids decreased. Plasma glucose, insulin, and insulin-like growth factor-1 concentrations increased in all groups after dry-off. Glucose, insulin, and glucagon concentrations in plasma were higher in nonrestricted compared with restricted animals after dry-off. The experimental concentrate types marginally affected the investigated metabolic and endocrine factors, with the exception of elevated milk and plasma urea concentrations in cows fed the nitrogenic concentrate. Chemotactic and phagocytic activity of leukocytes were not affected by diets, feed restriction, or dry-off. Likewise, blood leukocyte mRNA abundance encoding for tumor necrosis factor α (TNF), heat shock protein family A (HSP70), and the glucose transporters (GLUT) 1 and 3 remained unchanged throughout the study period. Overall, the short-term negative energy balance induced by feed restriction was temporarily accompanied by metabolic adaptations, but did not alter the studied factors related to the immune system. Metabolic and endocrine adaptations supporting milk synthesis were continued during the first days after dry-off despite cessation of milking. Thus, the abrupt dry-off resulted in a short-term increase of glucose and triglyceride concentrations, with a delayed endocrine response to re-establish nutrient homeostasis in blood.

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“…Functional enrichment analysis of the candidate genes was carried out, and the candidate genes were enriched by DAVID ( https://david.ncifcrf.gov/ ) [ 24 ]. The highly enriched terms of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were collected.…”

Section: Methodsmentioning

confidence: 99%

miR-155-5p regulates hypoxia-induced pulmonary artery smooth muscle cell function by targeting PYGL

2022

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Pulmonary arterial hypertension (PAH) is a cardiovascular disease that has high incidence and causes massive deaths. miR-155-5p/PYGL pathway was revealed to play a crucial role in PAH by weighted gene co-expression network analysis (WGCNA). The potential mechanism of miR-155-5p in regulating hypoxia-induced pulmonary artery smooth muscle cell (PASMC) function was analyzed through in vitro experiments. Hypoxia treatment stimulated the proliferation of PASMCs and increased the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α). At the same time, revealed by qRT-PCR and western blot, the level of miR-155-5p was raised, and the level of PYGL was decreased in hypoxia-induced PASMCs. Through CCK-8 assay, transwell assay and flow cytometry, it was revealed that miR-155-5p inhibitor remarkably inhibited the cell proliferation and migration and decreased the proportion of hypoxia-stimulated PASMCs in S and G2/M phases. Dual-luciferase reporter system was subsequently applied to validate the straight regulation of miR-155-5p on PYGL based on the analysis of online database. Furthermore, siPYGL was revealed to reverse the influence of miR-155-5p inhibitor on hypoxia-induced PASMCs. These outcomes indicate that the increased level of miR-155-5p in hypoxia-stimulated PASMCs could enhance the cell proliferation, cell migration, and cell cycle progression by targeting PYGL directly. This study may supply novel treatment strategies for PAH. Abbreviations : PH, pulmonary hypertension; PAH, pulmonary arterial hypertension; WGCNA, weighted gene co-expression network analysis; PASMCs, pulmonary artery smooth muscle cells; VEGF, vascular endothelial growth factor; HIF-1α, hypoxia-inducible factor-1α; SMCs, smooth muscle cells; DEGs, differentially expressed genes; GEO, Gene Expression Omnibus; GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; FBS, fetal bovine serum; OD, optical density; BCA, bicinchoninic acid; PVDF, polyvinylidene fluoride; PBS, phosphate-buffered saline; BP, biological process; MF, molecular function; CC, cell component.

show abstract

Relationships between metabolic profiles and gene expression in liver and leukocytes of dairy cows in early lactation

Cited by 27 publications

References 104 publications

A 12 kb multi-allelic copy number variation encompassing a GC gene enhancer is associated with mastitis resistance in dairy cattle

A 12 kb multi-allelic copy number variation encompassing a GC gene enhancer is associated with mastitis resistance in dairy cattle

Effect of different dietary regimens at dry-off on performance, metabolism, and immune system in dairy cows

miR-155-5p regulates hypoxia-induced pulmonary artery smooth muscle cell function by targeting PYGL

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