Differential gene expression in dairy cows under negative energy balance and ketosis: A systematic review and meta-analysis

Abstract Development of ketosis in high-producing dairy cows contributes to animal health issues and highlights the need for better understanding the genetic basis of metabolic diseases. Thus, the aim of this study was to evaluate the pattern of differential gene expression in liver of cows under negative energy balance (NEB), subclinical, and clinical ketosis through a systematic review and meta-analysis of published gene expression and genome-wide association studies (GWAS) results. After screening of the 118 articles found in the systematic review, 20 articles were included in the analysis. For this, 430 significant SNPs identified by GWAS were investigated to see if they were located within genes reported in gene expression studies. A permutation approach was used to identify the biological pathways associated with the metabolic conditions studied. A gene network was created using the differentially expressed genes harboring significant SNPs and a QTL enrichment analysis was performed to identify potential positional candidate loci. This study revealed 14 genes that are differentially expressed in the liver of cows in different metabolic conditions, which harbor 24 significant polymorphisms in reported GWAS. Three significant metabolic pathways were associated with NEB, subclinical and clinical ketosis. In addition, two important genes, PPARA and ACACA, were identified as differentially expressed in the three metabolic conditions. Gene network analysis revealed co-expression interactions among 34 genes associated with functions involving fatty acid transport and metabolism. The genes FN1 and PTK2 were enriched for QTL previously associated with the trait “ketosis” on chromosome 2 and with the trait “milk iron content” on chromosome 14, respectively. These findings improve the understanding of negative energy balance and ketosis in dairy cows, which could enhance selection for cows less susceptible to ketosis and help with the development of potential biomarkers for early diagnosis and prevention of ketosis.

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Impact of negative energy balance on transcriptomic profiles of three endometrial cell types isolated by laser capture microdissection in postpartum dairy cows

10.21203/rs.3.rs-36108/v1 ◽

2020 ◽

Author(s):

Wiruntita Chankeaw ◽

Sandra Lignier ◽

Christophe Richard ◽

Theodoros Ntallaris ◽

Mariam Raliou ◽

...

Keyword(s):

Gene Expression ◽

Energy Balance ◽

Dairy Cows ◽

Cell Types ◽

Negative Energy ◽

Negative Energy Balance ◽

Specific Response ◽

Endometrial Cell ◽

Expression Of Genes ◽

Constitutive Gene Expression

Abstract Background: In postpartum dairy cows, the energy needs to satisfy high milk production induces a more or less pronounced Negative Energy Balance (NEB) status. NEB associated with fat mobilization impairs reproductive function. This study investigated the specific impact of NEB on gene expression in the three main types of endometrial cells at time planned for insemination and implantation. Endometrial cell types (stromal, glandular and luminal epithelial cells) were isolated by laser micro-dissection allowing the study of constitutive gene expression and their specific response to NEB. Methods: Nine Swedish Red cows receiving a control diet or a mild restricted diet to induce differences of energy balance were categorized into mild (MNEB, n = 5) and severe negative energy balance (SNEB, n = 4). The three endometrial cell types: luminal (LE), glandular (GE) epithelium and stroma (ST) were collected by laser microdissection from endometrial biopsies performed at 80 days postpartum. Results: Transcriptome profiles obtained by RNA sequencing revealed differences in constitutive gene expression between the three cells types and also differences in specific responses related to the severity of NEB. Number of differentially expressed genes between SNEB and MNEB cows was higher in ST than in LE and GE, respectively. SNEB was associated with differential expression of genes related to metabolic processes and embryo-maternal interactions in ST. Under-expression of genes related to cell structure was found in GE whereas genes related to pro-inflammatory pathways were over-expressed. Genes associated to adaptive immunity were under-expressed in LE. Conclusion: The three different main cells types of the endometrium, have very different patterns of gene expression. The severity of NEB after calving is associated with changes in gene expression at time of breeding. Specific alterations in GEs are associated with activation of pro-inflammatory mechanisms. Concomitantly, changes in the expression of genes related to cell to cell interactions and maternal recognition of pregnancy takes place in ST. The combination of these effects possibly altering the uterine environment and embryo maternal interactions may negatively influence the establishment of pregnancy.

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Impact of the severity of negative energy balance on gene expression in the subcutaneous adipose tissue of periparturient primiparous Holstein dairy cows: Identification of potential novel metabolic signals for the reproductive system

PLoS ONE ◽

10.1371/journal.pone.0222954 ◽

2019 ◽

Vol 14 (9) ◽

pp. e0222954

Author(s):

Namya Mellouk ◽

Christelle Rame ◽

Delphine Naquin ◽

Yan Jaszczyszyn ◽

Jean-Luc Touzé ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Energy Balance ◽

Dairy Cows ◽

Reproductive System ◽

Subcutaneous Adipose Tissue ◽

Negative Energy ◽

Negative Energy Balance ◽

Subcutaneous Adipose ◽

Holstein Dairy Cows

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Pleiotropic effects of negative energy balance in the postpartum dairy cow on splenic gene expression: repercussions for innate and adaptive immunity

Physiological Genomics ◽

10.1152/physiolgenomics.90394.2008 ◽

2009 ◽

Vol 39 (1) ◽

pp. 28-37 ◽

Cited By ~ 33

Author(s):

D. G. Morris ◽

S. M. Waters ◽

S. D. McCarthy ◽

J. Patton ◽

B. Earley ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Energy Balance ◽

Dairy Cows ◽

Adaptive Immunity ◽

Dairy Cow ◽

Negative Energy ◽

Negative Energy Balance ◽

Innate And Adaptive Immunity ◽

Early Postpartum

Increased energy demands to support lactation, coupled with lowered feed intake capacity results in negative energy balance (NEB) and is typically characterized by extensive mobilization of body energy reserves in the early postpartum dairy cow. The catabolism of stored lipid leads to an increase in the systemic concentrations of nonesterified fatty acids (NEFA) and β-hydroxy butyrate (BHB). Oxidation of NEFA in the liver result in the increased production of reactive oxygen species and the onset of oxidative stress and can lead to disruption of normal metabolism and physiology. The immune system is depressed in the peripartum period and early lactation and dairy cows are therefore more vulnerable to bacterial infections causing mastitis and or endometritis at this time. A bovine Affymetrix oligonucleotide array was used to determine global gene expression in the spleen of dairy cows in the early postpartum period. Spleen tissue was removed post mortem from five severe NEB (SNEB) and five medium NEB (MNEB) cows 15 days postpartum. SNEB increased systemic concentrations of NEFA and BHB, and white blood cell and lymphocyte numbers were decreased in SNEB animals. A total of 545 genes were altered by SNEB. Network analysis using Ingenuity Pathway Analysis revealed that SNEB was associated with NRF2-mediated oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, natural killer cell signaling, p53 signaling, downregulation of IL-15, BCL-2, and IFN-γ; upregulation of BAX and CHOP and increased apoptosis with a potential negative impact on innate and adaptive immunity.

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Metabolic Adaptations to Dynamic Energy Requirements during Lactation and Pregnancy in Dairy Cows with Varying Proportions of Holstein and Simmental Breed

Proceedings ◽

10.3390/ieca2020-08833 ◽

2020 ◽

Vol 73 (1) ◽

pp. 9

Author(s):

Deise Aline Knob ◽

André Thaler Neto ◽

Helen Schweizer ◽

Anna Weigand ◽

Roberto Kappes ◽

...

Keyword(s):

Energy Balance ◽

Dairy Cows ◽

Fixed Effects ◽

Mixed Model ◽

Negative Energy ◽

Negative Energy Balance ◽

Repeated Measure ◽

Holstein Cows ◽

Mixed Model Analysis ◽

Genetic Groups

Depending on the breed or crossbreed line, cows have to cope with a more or less severe negative energy balance during the period of high milk yields in early lactation, which can be detected by beta-hydroxybutyrate (BHBA) and non-esterified fatty acids (NEFAs) in blood. Preventing cows from undergoing a severe negative energy balance by breeding and/or feeding measures is likely to be supported by the public and may help to improve the sustainability of milk production. The aim was to compare BHBA and NEFA concentrations in the blood of Holstein and Simmental cows and their crosses during the prepartum period until the end of lactation. In total, 164 cows formed five genetic groups according to their theoretic proportion of Holstein and Simmental genes as follows: Holstein (100% Holstein; n = 9), R1-Hol (51–99% Holstein; n = 30), F1 crossbreds (50% Holstein, 50% Simmental; n = 17), R1-Sim (1–49% Holstein; n = 81) and Simmental (100% Simmental; n = 27). NEFA and BHBA were evaluated once a week between April 2018 and August 2019. A mixed model analysis with fixed effects breed, week (relative to calving), the interaction of breed and week, parity, calving year, calving season, milking season, and the repeated measure effect on cows was used. Holstein cows had higher NEFAs (0.196 ± 0.013 mmol/L), and Simmental cows had the lowest NEFA concentrations (0.147 ± 0.008 mmol/L, p = 0.03). R1-Sim, F1 and R1-Hol cows had intermediate values (0.166 ± 0.005, 0.165 ± 0.010, 0.162 ± 0.008 mmol/L; respectively). The highest NEFA value was found in the first week after calving (0.49 ± 0.013 mmol/L). BHBA did not differ among genetic groups (p = 0.1007). There was, however, an interaction between the genetic group and week (p = 0.03). While Simmental, R1-Sim and F1 cows had the highest BHBA value, the second week after calving (0.92 ± 0.07 and 1.05 ± 0.04, and 1.10 ± 0.10 mmol/L, respectively), R1-Hol and Holstein cows showed the BHBA peak at the fourth week after calving (1.16 ± 0.07 and 1.36 ± 0.12 mmol/L, respectively). Unexpectedly, Holstein cows had a high BHBA peak again at week 34 after calving (1.68 ± 0.21 mmol/L). The genetic composition of the cows affects NEFA and BHBA. Simmental and R1-Sim cows mobilize fewer body reserves after calving. Therefore, dairy cows with higher degrees of Simmental origin might be more sustainable in comparison with Holstein genetics in the present study.

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The Capacity of Holstein-Friesian and Simmental Cows to Correct a Negative Energy Balance in Relation to Their Performance Parameters, Course of Lactation, and Selected Milk Components

Animals ◽

10.3390/ani11061674 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1674

Author(s):

Ilona Strączek ◽

Krzysztof Młynek ◽

Agata Danielewicz

Keyword(s):

Fatty Acid ◽

Energy Balance ◽

Dairy Cows ◽

Body Condition ◽

Body Condition Score ◽

Negative Energy ◽

Negative Energy Balance ◽

Holstein Friesian ◽

Condition Score ◽

Peak Lactation

A significant factor in improving the performance of dairy cows is their physiological ability to correct a negative energy balance (NEB). This study, using Simmental (SIM) and Holstein-Friesian (HF) cows, aimed to assess changes in NEB (non-esterified fatty acid; body condition score; and C16:0, C18:0, and C18:1) and its effect on the metabolic efficiency of the liver (β-hydroxybutyrate and urea). The effects of NEB on daily yield, production at peak lactation and its duration, and changes in selected milk components were assessed during complete lactation. Up to peak lactation, the loss of the body condition score was similar in both breeds. Subsequently, SIM cows more efficiently restored their BCS. HF cows reached peak lactation faster and with a higher milk yield, but they were less able to correct NEB. During lactation, their non-esterified fatty acid, β-hydroxybutyrate, C16:0, C18:0, C18:1, and urea levels were persistently higher, which may indicate less efficient liver function during NEB. The dynamics of NEB were linked to levels of leptin, which has anorectic effects. Its content was usually higher in HF cows and during intensive lactogenesis. An effective response to NEB may be exploited to improve the production and nutritional properties of milk. In the long term, it may extend dairy cows’ productive life and increase lifetime yield.

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Methods to increase reproducibility in differential gene expression via meta-analysis

Nucleic Acids Research ◽

10.1093/nar/gkw797 ◽

2016 ◽

Vol 45 (1) ◽

pp. e1-e1 ◽

Cited By ~ 66

Author(s):

Timothy E. Sweeney ◽

Winston A. Haynes ◽

Francesco Vallania ◽

John P. Ioannidis ◽

Purvesh Khatri

Keyword(s):

Gene Expression ◽

Differential Gene Expression ◽

Meta Analysis ◽

Differential Gene

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Changes in selected biochemical parameters during subclinical and clinical ketosis in dairy cows

Medycyna Weterynaryjna ◽

10.21521/mw.6133 ◽

2019 ◽

Vol 74 (10) ◽

pp. 6133-2019

Author(s):

YUANYUAN CHEN ◽

ZHIHAO DONG ◽

RUIRUI LI ◽

CHUANG XU

Keyword(s):

Lipid Metabolism ◽

Energy Balance ◽

Dairy Cows ◽

Perinatal Period ◽

Oxidative Capacity ◽

Negative Energy ◽

Negative Energy Balance ◽

Fibroblast Growth Factor 21 ◽

Acid Oxidation ◽

Subclinical Ketosis

Negative energy balance (NEB) is a common pathological cause of ketosis. As the major organs of lipid metabolism, the liver and fat tissue take part in regulating lipid oxidative capacity and energy demands, which is also a key metabolic pathway that regulates NEB development during the perinatal period. Fibroblast Growth Factor 21 (FGF21) is a novel metabolic regulator involved in the control of fatty acid oxidation and lipid metabolism during a prolonged negative energy balance. Our study determined a correlation between serum FGF21 and β-hydroxybutyric acid (BHBA) levels in dairy cows with ketosis. We used sixty cows with low milk yield, abnormal glucose metabolism, and ketosis. Serum FGF21 and BHBA levels were measured using commercial kits. Serum FGF21 increased with increasing BHBA levels up to 1.6 mmol/L. At BHBA levels > 1.6 mmol/L, FGF21 decreased. Serum FGF21 levels were positively associated with BHBA levels, particularly in dairy cows with subclinical ketosis (r = 0.647, P < 0.01). At BHBA levels between 1.2 mmol/L and 1.6 mmol/L, FGF21 was more closely correlated with BHBA than with other metabolic parameters. At BHBA levels > 1.6 mmol/L, the association between FGF21 and BHBA was not significant. In conclusion, our results show that FGF21 was closely related with SK in cows. FGF21 may be a promising regulator in the prevention of subclinical ketosis.

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Effect of acute nutritional restriction on periovulatory oestradiol and IGF-I in beef heifers

Proceedings of the British Society of Animal Science ◽

10.1017/s1752756200005974 ◽

2001 ◽

Vol 2001 ◽

pp. 215-215 ◽

Cited By ~ 1

Author(s):

D.R. Mackey ◽

A.R.G. Wylie ◽

J.F. Roche ◽

J.M. Sreenan ◽

M.G. Diskin

Keyword(s):

Energy Balance ◽

Dairy Cows ◽

Postpartum Period ◽

Negative Energy ◽

Oestrous Cycle ◽

Negative Energy Balance ◽

Beef Heifers ◽

Igf I ◽

Nutritional Restriction

Severe negative energy balance (NEB) in the postpartum period of dairy cows may be associated with declining fertility but the mechanisms by which nutrition influences reproduction are complex, poorly understood and confounded by lactation. Hence, both chronic and acute nutritional restriction of beef heifers have been used as models to examine the effects of NEB on ovarian and endocrine responses in the absence of lactation. Plasma IGF-I concentrations gradually decreased until the onset of anoestrus (Stagg et al., 1999) but concentrations may be confounded with stage of the oestrous cycle, especially around ovulation (Mackey et al., 2000). Therefore, the aim of this study was to examine the effect of nutritional restriction on periovulatory oestradiol (E2) and IGF-I concentrations.

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