Adaptations of hepatic lipid metabolism and mitochondria in dairy cows with mild fatty liver.

Published on Oct 1, 2018in Journal of Dairy Science3.333
· DOI :10.3168/JDS.2018-14546
Xiliang Du12
Estimated H-index: 12
(JLU: Jilin University),
Taiyu Shen5
Estimated H-index: 5
(JLU: Jilin University)
+ 13 AuthorsXinwei Li23
Estimated H-index: 23
(JLU: Jilin University)
Sources
Abstract
ABSTRACT The inevitable deficiency in nutrients and energy at the onset of lactation requires an optimal adaptation of the hepatic metabolism to overcome metabolic stress. Fatty liver is one of the main health disorders after parturition. Therefore, to investigate changes in hepatic lipid metabolic status and mitochondria in dairy cows with mild fatty liver, liver and blood samples were collected from healthy cows (n = 15) and cows with mild fatty liver (n = 15). To determine the effects of palmitic acids (PA), one of the major component of fatty acids, on lipid metabolism and mitochondria in vitro, calf hepatocytes were isolated from healthy calves and treated with various concentrations of PA (0, 50, 100, and 200 μM). Dairy cows with mild fatty liver displayed hepatic lipid accumulation. The protein levels of sterol regulatory element-binding protein 1c (SREBP-1c) and peroxisome proliferator-activated receptor-α (PPARα) and mRNA levels of acetyl CoA carboxylase 1 (ACC1), fatty acid synthase (FAS), acyl-CoA oxidase (ACO), and carnitine palmitoyltransferase 1A (CPT1A) were significantly higher in dairy cows with mild fatty liver than in control cows. The hepatic mitochondrial DNA content, mRNA levels of oxidative phosphorylation complexes I to V (CO 1-V), protein levels of cytochrome c oxidase subunit IV (COX IV), voltage dependent anion channel 1 (VDAC1), peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α) and nuclear respiratory factor 1 (NRF1), and adenosine triphosphate (ATP) content were all markedly increased in the liver of dairy cows with mild fatty liver compared with healthy cows. The PA treatment significantly increased lipid accumulation; protein levels of SREBP-1c and PPARα; and mRNA levels of ACC1, FAS, ACO, and CPT1A in calf hepatocytes. Moreover, the mitochondrial DNA content, mRNA levels of CO 1-V, protein levels of COX IV, VDAC1, PGC-1α, NRF1, mitochondrial transcription factor A, and ATP content were significantly increased in PA-treated hepatocytes compared with control hepatocytes. The protein level of mitofusin-2 was significantly decreased in PA-treated groups. In conclusion, lipid synthesis and oxidation, number of mitochondria, and ATP production were increased in the liver of dairy cows with mild fatty liver and PA-treated calf hepatocytes. These changes in hepatic mitochondria and lipid metabolism may be the adaptive mechanism of dairy cows with mild fatty liver.
📖 Papers frequently viewed together
10 Authors (Xinwei Li, ..., Guowen Liu)
75 Citations
88 Citations
11 Authors (Yu Li, ..., Jinjie Wu)
2 Citations
References52
Newest
#1Wenwen Gao (JLU: Jilin University)H-Index: 5
#2Xiliang Du (JLU: Jilin University)H-Index: 12
Last. Xinwei Li (JLU: Jilin University)H-Index: 23
view all 9 authors...
: The aim of this study was to investigate the changes in hepatic oxidative phosphorylation (OXPHOS) complexes (COs) in patients and cows with non-alcoholic steatohepatitis (NASH) and to investigate the mechanism that links mitochondrial dysfunction and hepatic insulin resistance induced by non-esterified fatty acids (NEFAs). Patients and cows with NASH displayed high blood NEFAs, TNF-α and IL-6 concentrations, mitochondrial dysfunction and insulin resistance. The protein levels of peroxisome pr...
22 CitationsSource
#1Xiliang Du (JLU: Jilin University)H-Index: 12
#2Yiwei Zhu (JLU: Jilin University)H-Index: 9
Last. Guowen Liu (JLU: Jilin University)H-Index: 27
view all 14 authors...
ABSTRACT The hepatic growth hormone (GH)–insulin-like growth factor (IGF)-I axis is essential for regulating intrahepatic lipid metabolism. Ketotic cows are characterized by high blood concentrations of fatty acids and β-hydroxybutyrate (BHB), which display lipotoxicity. The aim of this study was to investigate changes in the hepatic GH–IGF-I axis in ketotic cows and to determine the effects of fatty acids and BHB on the GH–IGF-I axis in calf hepatocytes. Liver and blood samples were collected f...
49 CitationsSource
#1Xiliang DuH-Index: 12
#2Zhen ShiH-Index: 10
Last. Xinwei LiH-Index: 23
view all 9 authors...
Dairy cows with ketosis are characterized by oxidative stress, hepatic damage, and hyperketonemia. Acetoacetate (AA) is the main component of ketone bodies in ketotic cows, and is associated with the above pathological process. However, the potential mechanism was not illuminated. Therefore, the aim of this study was to investigate the mechanism of AA-induced hepatic oxidative damage in ketotic cows. Compared with healthy cows, ketotic cows exhibited severe oxidative stress and hepatic damage. M...
107 CitationsSource
#1Ngoc-Thuy Ha (GAU: University of Göttingen)H-Index: 6
#2Cord Drögemüller (University of Bern)H-Index: 35
Last. Josef Johann Gross (University of Bern)H-Index: 17
view all 7 authors...
ABSTRACT During early lactation, dairy cows experience a severe metabolic load often resulting in the development of various diseases. The inevitable deficiency in nutrients and energy at the onset of lactation requires an optimal adaptation of the hepatic metabolism to overcome metabolic stress. We conducted a whole-liver transcriptome analysis for the transition cow to identify novel factors crucial for metabolic adaptation. Liver samples were obtained from 6 Red Holstein dairy cows (parity 2 ...
13 CitationsSource
#1Xiliang Du (JLU: Jilin University)H-Index: 12
#2Yuchen Yang (JLU: Jilin University)H-Index: 4
Last. Guowen LiuH-Index: 27
view all 14 authors...
// Xiliang Du 1 , Yuchen Yang 1 , Chuang Xu 2 , Zhicheng Peng 1 , Min Zhang 1 , Lin Lei 1 , Wenwen Gao 1 , Yuhao Dong 1 , Zhen Shi 1 , Xudong Sun 1 , Zhe Wang 1 , Xiaobing Li 1 , Xinwei Li 1 and Guowen Liu 1 1 Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China 2 College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China Correspondene to: Xinwei Li, email: lixinwei100@...
22 CitationsSource
#1L. Laubenthal (University of Bonn)H-Index: 5
#2L. RudaH-Index: 4
Last. S. Häussler (University of Bonn)H-Index: 12
view all 9 authors...
With the onset of lactation, dairy cows with a body condition score >3.5 are sensitive to oxidative stress and metabolic disorders. Adipose tissue (AT) can adapt to varying metabolic demands and energy requirements by the plasticity of its size during lactation. In AT, angiogenesis is necessary to guarantee sufficient oxygen and nutrient supply for adipocytes. Cellular energy metabolism is reflected mainly by mitochondria, which can be quantified by the mitochondrial DNA copy number per cell. In...
6 CitationsSource
#1Nishanth E. Sunny (UF: University of Florida)H-Index: 20
#2Fernando Bril (UF: University of Florida)H-Index: 25
Last. Kenneth Cusi (UF: University of Florida)H-Index: 71
view all 3 authors...
Nonalcoholic fatty liver disease (NAFLD) is prevalent in patients with obesity or type 2 diabetes. Nonalcoholic steatohepatitis (NASH), encompassing steatosis with inflammation, hepatocyte injury, and fibrosis, predisposes to cirrhosis, hepatocellular carcinoma, and even cardiovascular disease. In rodent models and humans with NAFLD/NASH, maladaptation of mitochondrial oxidative flux is a central feature of simple steatosis to NASH transition. Induction of hepatic tricarboxylic acid cycle closel...
110 CitationsSource
#2Celia BañulsH-Index: 23
Last. Victor M. Victor (University of Valencia)H-Index: 54
view all 6 authors...
Abstract Mitochondria play a key role in maintaining cellular metabolic homeostasis. These organelles have a high plasticity and are involved in dynamic processes such as mitochondrial fusion and fission, mitophagy and mitochondrial biogenesis. Type 2 diabetes is characterised by mitochondrial dysfunction, high production of reactive oxygen species (ROS) and low levels of ATP. Mitochondrial fusion is modulated by different proteins, including mitofusin-1 (MFN1), mitofusin-2 (MFN2) and optic atro...
146 CitationsSource
#1Xiliang Du (JLU: Jilin University)H-Index: 12
#2Liang ChenH-Index: 3
Last. Guowen Liu (JLU: Jilin University)H-Index: 27
view all 10 authors...
Background/Aims: Dairy cows with ketosis are characterized by oxidative stress and hepatic damage. The aim of this study was to investigate hepatic oxidative stress and the apoptotic status of ketotic cows, as well as the underlying apoptosis pathway. Methods: The blood aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH) and gamma-glutamyl transferase (GGT) activities and the haptoglobin (HP), serum amyloid A (SAA) and serum apoptotic cytokeratin 18 n...
60 CitationsSource
#1Xudong Sun (JLU: Jilin University)H-Index: 7
#2Xue YuanH-Index: 9
Last. Guowen Liu (JLU: Jilin University)H-Index: 27
view all 9 authors...
Background/Aims: Subacute ruminal acidosis (SARA) is a common disease in high-producing lactating cows. Rumenitis is the initial insult of SARA and is associated with the high concentrations of histamine produced in the rumen of dairy cows during SARA. However, the exact mechanism remains unclear. The objective of the current study is to investigate whether histamine induces inflammation of rumen epithelial cells and the underlying mechanism of this process. Methods: Bovine rumen epithelial cell...
77 CitationsSource
Cited By34
Newest
#1Melanie Schären (Leipzig University)H-Index: 6
#2Bjoern Riefke (Bayer)H-Index: 4
Last. Alexander Starke (Leipzig University)H-Index: 9
view all 16 authors...
The liver plays a central role in the postpartum (PP) energy metabolism of the transition dairy cow; however, studies describing the liver metabolome during this period were lacking. The aim of the presented study was therefore to compare the alterations in the liver and blood metabolome of transition dairy cows. For this purpose, an on-farm trial with 80 German Holstein cows (mean lactation number: 3.9; range: 2-9) was performed, with thorough documentation of clinical traits and clinical chemi...
2 CitationsSource
#1K.M. Kennedy (Leibniz Association)
Last. B. Kuhla (Leibniz Association)H-Index: 11
view all 4 authors...
ABSTRACT Improving feed utilization efficiency in dairy cattle could have positive economic and environmental effects that would support the sustainability of the dairy industry. Identifying key differences in metabolism between high and low feed-efficient animals is vital to enhancing feed conversion efficiency. Therefore, our objectives were (1) to determine whether cows grouped by either high or low feed efficiency have measurable differences in net fat and carbohydrate metabolism that accoun...
Source
#1Yan Huang (NWAFU: Northwest A&F University)H-Index: 2
#2Chenxu Zhao (NWAFU: Northwest A&F University)H-Index: 1
Last. Jianguo Wang (NWAFU: Northwest A&F University)H-Index: 10
view all 10 authors...
Abstract During the periparturient transition period, negative energy balance (NEB) characterized by high concentrations of non-esterified fatty acids (NEFA) may cause fatty liver and ketosis in dairy cows. Previous studies have shown that the protein kinase R-like endoplasmic reticulum kinase (PERK) branch of the endoplasmic reticulum stress (ERS) response plays an important role in lipid metabolism in hepatocytes. This study, therefore, investigated the role of the PERK-branch in NEFA-induced ...
1 CitationsSource
#1Yuxiang Song (JLU: Jilin University)H-Index: 8
#2Juan J. Loor (UIUC: University of Illinois at Urbana–Champaign)H-Index: 68
Last. Xinwei Li (JLU: Jilin University)H-Index: 23
view all 12 authors...
ABSTRACT Ketosis is a common metabolic disorder in high-producing dairy cows during the peripartal period. Negative energy balance leads to increased circulating levels of nonesterified fatty acids (NEFA) and β-hydroxybutyrate (BHB), consequently increasing the risk of ketosis. It is well-known that NEFA and BHB can induce lipotoxicity and oxidative stress in bovine tissues/organs including the liver and adipose tissue. Although the mammary gland is one important site for NEFA and BHB metabolism...
1 CitationsSource
#1Yanqing Li (JLU: Jilin University)H-Index: 11
#2Yan Jiao (JLU: Jilin University)H-Index: 11
Last. Jing Su (JLU: Jilin University)H-Index: 22
view all 6 authors...
The recovery of blood supply after a period of myocardial ischaemia does not restore the heart function and instead results in a serious dysfunction called myocardial ischaemia-reperfusion injury (IRI), which involves several complex pathophysiological processes. Mitochondria have a wide range of functions in maintaining the cellular energy supply, cell signalling and programmed cell death. When mitochondrial function is insufficient or disordered, it may have adverse effects on myocardial ischa...
Source
#1Riani Ananda Nunes Soares (U of G: University of Guelph)
#2Giovana Vargas (U of G: University of Guelph)H-Index: 1
Last. E. J. Squires (U of G: University of Guelph)H-Index: 32
view all 7 authors...
ABSTRACT Development of ketosis in high-producing dairy cows contributes to several animal health issues and highlights the need for a better understanding of the genetic basis of metabolic diseases. To evaluate the pattern of differential gene expression in the liver of cows under negative energy balance (NEB), and under subclinical and clinical ketosis, a meta-analysis of gene expression and genome-wide association studies results was performed. An initial systematic review identified 118 arti...
Source
ABSTRACT Dairy cows with fatty liver exhibit hepatic lipid accumulation and disturbances in fatty acid oxidation and lipid transport. Phosphatase and tensin homolog (PTEN), a lipid phosphatase, regulates intrahepatic fatty acid oxidation and lipid transport in mice. Whether PTEN play a role in fatty acid oxidation and very low density lipoprotein (VLDL) assembly in calf hepatocytes are unknown. Hepatocytes isolated from 3 healthy female Holstein calves (1 d old, 30–40 kg) were infected with empt...
Source
#1Bingbing ZhangH-Index: 5
#2Wei YangH-Index: 8
Last. Chuang XuH-Index: 7
view all 10 authors...
Fatty liver disease is one of the most common disorders afflicting dairy cows during the postpartum period, and is associated with increased blood non-esterified fatty acid (NEFA) uptake by the liver. Major long-chain fatty acids (LCFA) in NEFA are palmitic (PA), palmitoleic (POA), stearic (SA), oleic (OA), and linoleic (LA) acid. In order to investigate the characteristics of lipid accumulation and injury caused by these NEFA, primary calf hepatocytes were isolated and challenged for 12 h with ...
Source
#1Bingbing ZhangH-Index: 5
#2Ming LiH-Index: 8
Last. Chuang XuH-Index: 7
view all 11 authors...
ABSTRACT The store-operated Ca2+ 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 o...
Source
#1Chang ZhaoH-Index: 2
#1Chang ZhaoH-Index: 2
Last. Chuang XuH-Index: 2
view all 6 authors...
Background Subclinical ketosis (SCK) causes economic losses in the dairy industry because it reduces the milk production and reproductive performance of cows. Hypothesis/objectives To evaluate whether carboxymethyl chitosan-loaded reduced glutathione (CMC-rGSH) nanoparticles can alleviate the incidence or degree of SCK in a herd. Animals Holstein dairy cows 21 days postpartum (n = 15). Methods The trial uses a prospective study. Five cows with serum β-hydroxybutyric acid (BHBA) ≥1.20 mmol/L and ...
2 CitationsSource