Serum hepatokines in dairy cows: periparturient variation and changes in energy-related metabolic disorders

Wang, Jianguo; Zhu, Xiaoyan; Guang-hui, She; Kong, Yezi; Guo, Yazhou; Wang, Zhe; Liu, Zhaoxi; Zhao, Bin

doi:10.1186/s12917-018-1560-7

Cited by 24 publications

(29 citation statements)

References 54 publications

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“…Many studies have found that BHBA is a predominant and stable blood ketone body in ruminant ketosis [4,10], which, therefore, has been widely used for clinically diagnosing and classifying ketosis in dairy cows [11]. Furthermore, a large number of molecular biomarkers have been also identified to be associated with ketosis, such as milk fatty acids [12], serum hepatokines [13], inflammatory biomarkers [14], methylglyoxal [2], metabolites [15], mineral elements [16], protein profiling [17], and amino acids [18] in blood.…”

Section: Introductionmentioning

confidence: 99%

Clinical Ketosis-Associated Alteration of Gene Expression in Holstein Cows

Chen

Qin

et al. 2020

Genes

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Ketosis is one of the most prevalent transition metabolic disorders in dairy cows, and has been intrinsically influenced by both genetic and nutritional factors. However, altered gene expression with respective to dairy cow ketosis has not been addressed yet, especially at the genome-wide level. In this study, we recruited nine Holsteins diagnosed with clinical ketosis and ten healthy controls, for which whole blood samples were collected at both prepartum and postpartum. Four groups of blood samples were defined: from cows with ketosis at prepartum (PCK, N = 9) and postpartum (CK, N = 9), respectively, and controls at prepartum (PHC, N = 10) and postpartum (HC, N = 10). RNA-Seq approach was used for investigating gene expression, by which a total of 27,233 genes were quantified with four billion high-quality reads. Subsequently, we revealed 75 and four differentially expressed genes (DEGs) between sick and control cows at postpartum and prepartum, respectively, which indicated that sick and control cows had similar gene expression patterns at prepartum. Meanwhile, there were 95 DEGs between postpartum and prepartum for sick cows, which showed depressed changes of gene expression during this transition period in comparison with healthy cows (428 DEGs). Functional analyses revealed the associated DEGs with ketosis were mainly involved in biological stress response, ion homeostasis, AA metabolism, energy signaling, and disease related pathways. Finally, we proposed that the expression level of STX1A would be potentially used as a new biomarker because it was the only gene that was highly expressed in sick cows at both prepartum and postpartum. These results could significantly help us to understand the underlying molecular mechanisms for incidence and progression of ketosis in dairy cows.

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Section: Introductionmentioning

confidence: 99%

Clinical Ketosis-Associated Alteration of Gene Expression in Holstein Cows

Chen

Qin

et al. 2020

Genes

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“…Further elevation in its concentration has been recorded with ketosis and fatty liver disease in cows. 10 Adenoviralmediated overexpression of ANGPTL4 caused severe elevation in the concentration of plasma TG due to decreased VLDL clearance under the fasting conditions in mice. 8 Other supporting evidence demonstrated that the inhibition of ANGPTL4 to LPL in rich-LPL tissues, including adipose tissues, resulted in increasing the plasma TG concentrations.…”

Section: Discussionmentioning

confidence: 99%

“…10 Moreover, the plasma concentration of ANGPTL4 was found to be significantly higher in cows with fatty liver and ketosis than in healthy cows. 10 High concentrations of NEFA, which is an important indicator of NEB, notably stimulates the expression and secretion of ANGPTL4 in bovine hepatocytes in vitro. 11,12 Thus, NEB promotes the expression of ANGPTL4, thereby possibly contributing pathologically to energy metabolism disorders in dairy cows during their peripartum period.…”

Section: Introductionmentioning

confidence: 94%

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Angiopoietin‐like protein 4 promotes very‐low‐density lipoprotein assembly and secretion in bovine hepatocytes in vitro

et al. 2020

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In dairy cows, fatty liver is one of the most common metabolic diseases that occurs during the periparturient period. Angiopoietin‐like protein 4 (ANGPTL4) is a well‐known downstream target of peroxisome proliferator‐activated receptors (PPARs), which regulate the glucose and fatty acid metabolisms. The inhibition of lipoprotein lipase (LPL) activity interferes with the storage of triglycerides (TG) in adipocytes, which plays an essential role in lipid metabolism in rodents. However, it remains unclear whether ANGPTL4 is involved in the pathological process of fatty liver in dairy cows as a result of the regulation of the hepatocellular lipid transport system. This study intended to investigate the effect of ANGPTL4 on the very‐low‐density lipoprotein (VLDL) assembly and secretion in bovine hepatocytes. Bovine hepatocytes were isolated using a modified two‐step perfusion and collagenase digestion process, and treated with different concentrations of ANGPTL4 (0, 4, 12, and 24 ng/ml) for 24 hr. The results showed that a high concentration of ANGPTL4 could significantly increase the extracellular concentration of VLDL while reducing the intracellular content of TG. Thus, it was confirmed that ANGPTL4 could promote the transport of TG in the form of VLDL by partially regulating the expression of related proteins in hepatocytes, thereby contributing to the partial adaptive regulation of lipid transport in dairy cows.

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“…This disorder causes substantial economic losses due to decreased milk production, longer calving intervals, or removal from the herd (Bobe et al, 2004). The increase in plasma fatty acids due to negative energy balance around parturition is one of the causes of fatty liver, which is often followed by ketosis and insulin resistance (Wang et al, 2018). Recent data from dairy cows with fatty liver also revealed an association between increased plasma fatty acids and hepatic mitochondrial dysfunction (Du et al, 2018b).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial dysfunction and endoplasmic reticulum stress in calf hepatocytes are associated with fatty acid-induced ORAI calcium release-activated calcium modulator 1 signaling

Zhang

Yang

et al. 2020

Journal of Dairy Science

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The store-operated Ca 2+ entry (SOCE) moiety ORAI calcium release-activated calcium modulator 1 (ORAI1) located in the endoplasmic reticulum (ER) participates in key cellular functions such as protein folding, transport, and secretion, and lipid metabolism. We used an in vitro approach to test whether exogenous fatty acids alter ORAI1 signaling and to explore potential consequences on mitochondrial dysfunction and ER stress. First, hepatocytes isolated from 4 healthy female calves (1 d old, 40-50 kg) were challenged with a 1.2 mM mixture of oleic, linoleic, palmitic, stearic, and palmitoleic acids for 0.5, 1, 3, 6, 9, and 12 h to measure oxidative stress [intracellular reduced glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and hydrogen peroxide] and ER stress (protein abundance of PERK, IRE, ATF6, and GRP78). Concentrations of GSH and SOD decreased at 0.5 h, and MDA and hydrogen peroxide increased at 1 h; ER stress proteins increased at 6 h. To determine whether ER stress was caused by oxidative stress, primary calf hepatocytes were treated with the same 1.2 mM fatty acid mix or the reactive oxygen species (ROS) inhibitor N-acetylcysteine (NAC) for 6 h. We found that NAC prevented an increase in ER stress protein abundance. Next, the role of ORAI1 on ER stress was measured by transfecting hepatocytes with small interfering (si)ORAI1 or the ORAI1 inhibitor BTP2, followed by a challenge with 1.2 mM fatty acids for 3 h. Without inhibiting ORAI1, exogenous fatty acids upregulated ORAI1 mRNA and protein abundance, oxidative stress, ER stress proteins, and protein abundance of marker indicators of an opened mitochondrial permeability transition pore (mPTP). Inhibition with BPT2 or silencing via siO-RAI1 abrogated oxidative stress, including increased GSH concentration and SOD activity, decreased MDA, hydrogen peroxide, and ROS concentration; ER stress protein abundance was downregulated, and mitochondrial function was restored. Last, changes in markers of mPTP opening were evaluated by culturing hepatocytes for 6 h with the sarcoendoplasmic Ca 2+ ATPase inhibitor thapsigargin or the calcium ionophore ionomycin. We detected an increase in VDAC1, CLPP, and CypD protein abundance, all of which indicated opening of the mPTP. Overall, data from these in vitro studies suggest that ORAI1 mediates ER stress induced by high concentrations of fatty acids, in part through alleviating mitochondrial dysfunction caused by oxidative stress.

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Serum hepatokines in dairy cows: periparturient variation and changes in energy-related metabolic disorders

Cited by 24 publications

References 54 publications

Clinical Ketosis-Associated Alteration of Gene Expression in Holstein Cows

Clinical Ketosis-Associated Alteration of Gene Expression in Holstein Cows

Angiopoietin‐like protein 4 promotes very‐low‐density lipoprotein assembly and secretion in bovine hepatocytes in vitro

Mitochondrial dysfunction and endoplasmic reticulum stress in calf hepatocytes are associated with fatty acid-induced ORAI calcium release-activated calcium modulator 1 signaling

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