The effects of non-esterified fatty acids and β-hydroxybutyrate on the hepatic CYP2E1 in cows with clinical ketosis

Peng, Zheng; Li, Xiaobing; Wang, Zhe; Liu, Zhaoxi

doi:10.1017/s0022029919000025

Cited by 5 publications

(5 citation statements)

References 18 publications

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“…To our knowledge, there are no studies that specifically investigate the relationship between CYP1A2 and ketosis in cows. However, there are studies that examine the effect of ketosis on the expression of other cytochrome P450 genes in cows, for example, Peng et al [16] found that the expression of CYP2E1 was significantly upregulated in the liver of cows with clinical ketosis compared to healthy cows. Another study by Gaddis et al [17] indicate a relationship between ketosis and CYP26B1 gene expression.…”

Section: The Mrna Expression Of Hepatocytes-specific Genesmentioning

confidence: 99%

Short Culture of Bovine Hepatocytes Biopsied from Dairy Cows as a Model for Toxicological Studies—CYP 1A1 Activity Response to Zearalenone Treatment

Barć

Flaga

Kozubek

et al. 2023

IJMS

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This study presents a simple and cost-effective method for isolating hepatocytes from liver biopsies obtained from healthy and ketotic dairy cows, which can be utilized for studying cellular metabolism, drug toxicity, and hepatocyte-specific gene function and regulation. The expression of hepatocyte marker genes (G6PC, ALB, CYP1A2) was measured and found to be highest at 6 h post-isolation, with a subsequent decrease over time. Cells isolated from ketotic livers exhibited lower expression levels than those from healthy livers. Furthermore, for the functional characterization of ketotic hepatocytes, the cells were exposed to varying doses of zearalenone (ZEA). While doses of 10–50 µM did not affect cell viability, the highest dose of ZEA (100 µM) significantly decreased cell viability, as measured using XTT assay. Additionally, the potential induction of cytochrome P450 A1 (CYP1A1) by ZEA was found. Despite limitations such as a short-term culture, this model provides a useful tool for conducting toxicological research.

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Section: The Mrna Expression Of Hepatocytes-specific Genesmentioning

confidence: 99%

Short Culture of Bovine Hepatocytes Biopsied from Dairy Cows as a Model for Toxicological Studies—CYP 1A1 Activity Response to Zearalenone Treatment

Barć

Flaga

Kozubek

et al. 2023

IJMS

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“…2,5 Excess FFA accumulation overwhelms the hepatic processing capacity, inducing β-oxidation, which increases ketone levels and causes ketosis in dairy cows. 6,7 During ketosis, the supraphysiological circulating concentration of FFA causes mammary gland injury in dairy cows, as there is a high demand for mammary glands to produce milk. 2,8 Thus, ketosis has been associated with reduced milk yield during early lactation, causing economic losses.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Ketosis is a common metabolic disease that occurs in dairy cows during early lactation and is associated with several other periparturient diseases and reduced milk yield. , Ketosis susceptibility has been associated with an imbalance between the increased nutrient demands of lactation and a decrease in dry matter intake (DMI) during the postpartum transition period, , which elevates fat mobilization and increases fatty acid (FFA) concentration in the blood. , Excess FFA accumulation overwhelms the hepatic processing capacity, inducing β-oxidation, which increases ketone levels and causes ketosis in dairy cows. , During ketosis, the supraphysiological circulating concentration of FFA causes mammary gland injury in dairy cows, as there is a high demand for mammary glands to produce milk. , Thus, ketosis has been associated with reduced milk yield during early lactation, causing economic losses …”

Section: Introductionmentioning

confidence: 99%

Free Fatty Acids Induce Apoptosis of Mammary Epithelial Cells of Ketotic Dairy Cows via the Mito-ROS/NLRP3 Signaling Pathway

Chang,

Jia,

Dong

et al. 2023

J. Agric. Food Chem.

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Early lactation increases metabolic stress in ketotic dairy cows, leading to mitochondrial damage, apoptosis, and inflammatory response in mammary epithelial cells. The pyrin domain 3 (NLRP3) pathway involving the mitochondrial reactive oxygen species (Mito-ROS)-induced nucleotide-binding oligomerization domain-like receptor has been recognized as a key mechanism in this inflammatory response and cell apoptosis. This study aimed to elucidate the underlying regulatory mechanism of Mito-ROS–NLRP3 pathway-mediated mammary epithelial cell apoptosis in dairy cows with ketosis. Mitochondrial damage and cellular apoptotic program and NLRP3 inflammasome activation were observed in the mammary gland of ketotic cows. Similar damage was detected in MAC-T cells treated with exogenous fatty acids (FFAs). However, NLRP3 inhibitor MCC950 pretreatment or Mito-ROS scavenging by MitoTEMPO attenuated apoptosis in FFA-induced MAC-T cells by inhibiting the NLRP3 inflammasome pathway. These findings reveal that the Mito-ROS–NLRP3 pathway activation is a potent mechanism underlying mammary epithelial cell apoptosis in response to metabolic stress in ketotic dairy cows, which further contributes to reduced milk yield.

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“…The NEB initiates fat mobilization followed by a significant increase in blood concentrations of free fatty acids (FFA), which are the hallmark of NEB status (Duffield et al, 1998;Itle et al, 2015). Because an overload of hepatocytes with FFA is beyond the processing capacity of the liver, a large number of ketones is synthesized, among which the dominant is BHB, leading to the onset of ketosis (Peng et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Impaired autophagy aggravates oxidative stress in mammary gland of dairy cows with clinical ketosis

Yue

Loor

et al. 2022

Journal of Dairy Science

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When ketosis occurs, supraphysiological levels of free fatty acids (FFA) can cause oxidative injury to the mammary gland and autophagy can regulate the cellular oxidative status. The aim of this study was to investigate the autophagy status of mammary tissue and its associations with oxidative stress in healthy and clinically ketotic dairy cows. Mammary tissue and blood samples were collected from healthy cows [n = 15, β-hydroxybutyrate (BHB) <0.6 mM] and clinically ketotic cows (n = 15, BHB >3.0 mM) at 3 to 15 (average = 7) days in milk. For in vitro study, bovine mammary epithelial cells (BMEC) isolated from healthy cows were treated with 0, 0.3, 0.6, or 1.2 mM FFA for 24 h. Furthermore, BMEC were pretreated with 100 nM rapamycin, an autophagy activator, for 4 h or 50 mM 3-methyladenine (3-MA), an autophagy inhibitor, for 1 h, followed by treatment with or without FFA (1.2 mM) for another 24 h. Oxidation indicators and autophagyrelated protein abundance were measured. Compared with healthy cows, serum concentrations of FFA, BHB, and malondialdehyde were greater in clinically ketotic cows, but milk production (kg/d), milk protein (kg/d), activities of superoxide dismutase, catalase, and glutathione peroxidase were lower. Abundances of mRNA and protein of autophagy-related gene 5 (ATG5) and 7 (ATG7) were lower, but sequestosome-1 (SQSTM1, also called p62) greater in mammary tissue of clinically ketotic cows. The mRNA abundance of microtubuleassociated protein 1 light chain 3 (MAP1LC3, also called LC3) and protein abundance of LC3-II were lower in mammary tissue of clinically ketotic cows. In vitro, exogenous FFA increased the content of malondialdehyde and reactive oxygen species, but decreased the activities of superoxide dismutase, catalase, and plasma glutathione peroxidase. Compared with the 0 mM FFA group, abundance of ATG5, ATG7, LC3-II was greater, but p62 was lower in the 0.6 mM FFA-treated cells. Similarly, abundance of ATG5, ATG7, and LC3-II was lower, but p62 greater in the 1.2 mM FFA-treated cells relative to 0 mM FFA group. Culture with rapamycin alleviated oxidative stress induced by 1.2 mM FFA, whereas 3-MA aggravated it. Overall, results indicated that a low concentration (0.6 mM) of FFA can induce oxidative stress and activate autophagy in BMEC. At higher concentrations of FFA (1.2 mM), autophagy is impaired and oxidative stress is aggravated. Autophagy is a mechanism for BMEC to counteract FFA-induced stress. As such, it could serve as a potential target for further development of novel strategies against oxidative stress.

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The effects of non-esterified fatty acids and β-hydroxybutyrate on the hepatic CYP2E1 in cows with clinical ketosis

Cited by 5 publications

References 18 publications

Short Culture of Bovine Hepatocytes Biopsied from Dairy Cows as a Model for Toxicological Studies—CYP 1A1 Activity Response to Zearalenone Treatment

Short Culture of Bovine Hepatocytes Biopsied from Dairy Cows as a Model for Toxicological Studies—CYP 1A1 Activity Response to Zearalenone Treatment

Free Fatty Acids Induce Apoptosis of Mammary Epithelial Cells of Ketotic Dairy Cows via the Mito-ROS/NLRP3 Signaling Pathway

Impaired autophagy aggravates oxidative stress in mammary gland of dairy cows with clinical ketosis

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