Identification of Crucial Genetic Factors, Such as PPARγ, that Regulate the Pathogenesis of Fatty Liver Disease in Dairy Cows Is Imperative for the Sustainable Development of Dairy Industry

Shi, Kerong; Li, Ranran; Xu, Zuojun; Zhang, Qin

doi:10.3390/ani10040639

Cited by 23 publications

(24 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, another of the most important risk factors is histological evidence of hepatic inflammation [33,34] caused by acute inflammation and subacute inflammation [35]. Thus, dairy cows with fatty liver disease is a typical NAFLD animal model, good for revealing the pathology and pathogenesis of NAFLD [15]. The objective of the study is to reveal the molecular mechanism of pathogenesis for NAFLD by taking fatty liver diseased dairy cattle as research model, identifying potential important biological pathways and protein targets, and thereby further discovering the therapeutic targets.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Protein acetylation in mitochondria plays critical functions in the pathogenesis of fatty liver disease

Zhang

et al. 2020

BMC Genomics

Self Cite

View full text Add to dashboard Cite

Background: Fatty liver is a high incidence of perinatal disease in dairy cows caused by negative energy balance, which seriously threatens the postpartum health and milk production. It has been reported that lysine acetylation plays an important role in substance and energy metabolism. Predictably, most metabolic processes in the liver, as a vital metabolic organ, are subjected to acetylation. Comparative acetylome study were used to quantify the hepatic tissues from the severe fatty liver group and normal group. Combined with bioinformatics analysis, this study provides new insights for the role of acetylation modification in fatty liver disease of dairy cows. Results: We identified 1841 differential acetylation sites on 665 proteins. Among of them, 1072 sites on 393 proteins were quantified. Functional enrichment analysis shows that higher acetylated proteins are significantly enriched in energy metabolic pathways, while lower acetylated proteins are significantly enriched in pathways related to immune response, such as drug metabolism and cancer. Among significantly acetylated proteins, many mitochondrial proteins were identified to be interacting with multiple proteins and involving in lipid metabolism. Furthermore, this study identified potential important proteins, such as HADHA, ACAT1, and EHHADH, which may be important regulatory factors through modification of acetylation in the development of fatty liver disease in dairy cows and possible therapeutic targets for NAFLD in human beings. Conclusion: This study provided a comprehensive acetylome profile of fatty liver of dairy cows, and revealed important biological pathways associated with protein acetylation occurred in mitochondria, which were involved in the regulation of the pathogenesis of fatty liver disease. Furthermore, potential important proteins, such as HADHA, ACAT1, EHHADH, were predicted to be essential regulators during the pathogenesis of fatty liver disease. The work would contribute to the understanding the pathogenesis of NAFLD, and inspire in the development of new therapeutic strategies for NAFLD.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Fatty liver disease in dairy cows is a type of metabolic disorder. Little is known about the pathogenesis of perinatal fatty liver in dairy cows [15]. The objective of the present study is to investigate the possible role of protein acetylation in liver function during the transition period from dry milk to lactation in dairy cattle.…”

Section: Introductionmentioning

confidence: 99%

Protein acetylation in mitochondria plays critical functions in the pathogenesis of fatty liver disease

Zhang

et al. 2020

BMC Genomics

Self Cite

View full text Add to dashboard Cite

show abstract

“…This impairs liver functionality and increases inflammatory responses (Vernon, 2005). Around half of high-yielding dairy cows are estimated to develop moderate to severe fatty liver disease within the first 14 DIM (Shi et al, 2020). It is therefore probable that a significant proportion of the IMBAL cows in this study were so affected; they also had lower glucose levels.…”

Section: Metabolic Characteristics Of Bal and Imbal Cowsmentioning

confidence: 87%

“…These changes are reflected in circulating metabolite concentrations, with increased concentrations of nonesterified fatty acids (NEFA) and BHB and decreased concentrations of glucose. This may be associated with the development of hepatic steatosis (fatty liver disease; Vernon, 2005;Ingvartsen, 2006;Shi et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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

Wathes

Cheng

Salavati

et al. 2021

Journal of Dairy Science

View full text Add to dashboard Cite

Homeorhetic mechanisms assist dairy cows in the transition from pregnancy to lactation. Less successful cows develop severe negative energy balance (NEB), placing them at risk of metabolic and infectious diseases and reduced fertility. We have previously placed multiparous Holstein Friesian cows from 4 herds into metabolic clusters, using as biomarkers measurements of plasma nonesterified fatty acids, β-hydroxybutyrate, glucose and IGF-1 collected at 14 and 35 d in milk (DIM). This study characterized the global transcriptomic profiles of liver and circulating leukocytes from the same animals to determine underlying mechanisms associated with their metabolic and immune function.Liver biopsy and whole-blood samples were collected around 14 DIM for RNA sequencing. All cows with available RNA sequencing data were placed into balanced (BAL, n = 44), intermediate (n = 44), or imbalanced (IMBAL, n = 19) metabolic cluster groups. Differential gene expression was compared between the 3 groups using ANOVA, but only the comparison between BAL and IMBAL cows is reported. Pathway analysis was undertaken using DAVID Bioinformatic Resources (https: / / david .ncifcrf .gov/ ). Milk yields did not differ between BAL and IMBAL cows but dry matter intake was less in IMBAL cows and they were in greater energy deficit at 14 DIM (−4.48 v −11.70 MJ/d for BAL and IMBAL cows). Significantly differentially expressed pathways in hepatic tissue included AMPK signaling, glucagon signaling, adipocytokine signaling, and insulin resistance. Genes involved in lipid metabolism and cholesterol transport were more highly expressed in IMBAL cows but IGF1 and IG-FALS were downregulated. Leukocytes from BAL cows had greater expression of histones and genes involved in nucleosomes and cell division. Leukocyte expression of heat shock proteins increased in IMBAL cows, suggesting an unfolded protein response, and several key genes involved in immune responses to pathogens were upregulated (e.g., DEFB13, HP, OAS1Z, PTX3, and TLR4). Differentially expressed genes upregulated in IMBAL cows in both tissues included CD36, CPT1, KFL11, and PDK4, all central regulators of energy metabolism. The IMBAL cows therefore had greater difficulty maintaining glucose homeostasis and had dysregulated hepatic lipid metabolism. Their energy deficit was associated with a reduced capacity for cell division and greater evidence of stress responses in the leukocyte population, likely contributing to an increased risk of infectious disease.

show abstract

“…Fatty liver disease is a prevalently occurred metabolic disorder in dairy cows during the transition from dry period to early lactation in commercial farms throughout the world [1,2], which is caused by obesity before calving and dramatic physiological change and reduction of food intake after calving [3].…”

Section: Introductionmentioning

confidence: 99%

Genome-wide analysis identified proteins associated with mitochondrial function and inflammation activation crucially regulating the pathogenesis of fatty liver disease

Zhang

Liu

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Background Fatty liver disease prevalently occurs in commercial postpartum dairies, resulting in a worldwide high culling rate because of their subsequent limitations of production and reproduction performance. Results Fatty liver-specific proteome and acetylome analysis revealed that energy metabolism suppression closely associated with mitochondrial dysfunction and inflammation activation are shown to be remarkable biological processes underlying the development of fatty liver disease, thereby acetylation modification of proteins modulating these processes. Twenty pivotal genetic factors/genes that differentially expressing and being acetylation modified in liver were identified and proposed to regulate the pathogenesis of fatty liver dairies. These proteins were confirmed to be differentially expressing in individual liver tissues, eight of which being validated through immunohistochemistry assay. Conclusion This study provided a comprehensive proteome and acetylome profile of fatty liver of dairy cows, and revealed potential important biological processes and essential regulators in the pathogenesis of fatty liver disease. Expectantly, understanding the molecular mechanisms of the pathogenesis of fatty liver disease in dairies, as an animal model of non-alcoholic fatty liver disease (NAFLD) in human beings, which is a clinico-pathologically defined process associated with metabolic syndrome, could inspire and facilitate the development of efficacious therapeutic drugs on NAFLD.

show abstract

Identification of Crucial Genetic Factors, Such as PPARγ, that Regulate the Pathogenesis of Fatty Liver Disease in Dairy Cows Is Imperative for the Sustainable Development of Dairy Industry

Cited by 23 publications

References 92 publications

Protein acetylation in mitochondria plays critical functions in the pathogenesis of fatty liver disease

Protein acetylation in mitochondria plays critical functions in the pathogenesis of fatty liver disease

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

Genome-wide analysis identified proteins associated with mitochondrial function and inflammation activation crucially regulating the pathogenesis of fatty liver disease

Contact Info

Product

Resources

About