High concentrations of fatty acids and β-hydroxybutyrate impair the growth hormone-mediated hepatic JAK2-STAT5 pathway in clinically ketotic cows.

Published on Apr 1, 2018in Journal of Dairy Science3.333
· DOI :10.3168/JDS.2017-13234
Xiliang Du12
Estimated H-index: 12
(JLU: Jilin University),
Yiwei Zhu9
Estimated H-index: 9
(JLU: Jilin University)
+ 11 AuthorsGuowen Liu27
Estimated H-index: 27
(JLU: Jilin University)
Sources
Abstract
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 from healthy (n = 15) and clinically ketotic (n = 15) cows. Hepatocytes were isolated from calves and treated with various concentrations of GH, fatty acids, and BHB. The results showed that clinically ketotic cows displayed a high blood concentration of GH, a low blood concentration of IGF-I, and decreased hepatic GHR1A expression as well as impaired hepatic Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) signaling. In vitro, GH treatment induced activation of the JAK2-STAT5 pathway to increase the mRNA expression and secretion of IGF-I in calf hepatocytes. More importantly, treatment with fatty acids or BHB significantly inhibited GHR1A mRNA and JAK2 protein expression, as well as the STAT5 phosphorylation level and phospho-STAT5 nuclear translocation; these effects markedly reduced IGF1 mRNA expression and secretion in calf hepatocytes. In summary, these results indicate that high blood concentrations of fatty acids or BHB can impair the intrahepatic GH-mediated JAK2-STAT5 pathway and downregulate IGF-I expression and secretion in ketotic cows.
Download
📖 Papers frequently viewed together
113 Citations
109 Citations
80 Citations
References48
Newest
#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...
113 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@...
23 CitationsSource
#1Andrea M. Hanson (NDSU: North Dakota State University)H-Index: 3
#2Alicia T. Ickstadt (NDSU: North Dakota State University)H-Index: 2
Last. Mark A. Sheridan (NDSU: North Dakota State University)H-Index: 34
view all 5 authors...
Abstract Fish in aquatic habitats are exposed to increasing concentrations and types of environmental contaminants, including environmental estrogens (EE). While there is growing evidence to support the observation that endocrine-disrupting compounds (EDCs) possess growth-inhibiting effects, the mechanisms by which these physiological effects occur are poorly understood. In this study, we examined the direct effects of EE, specifically 17β-estradiol (E2), β-sitosterol (βS), and 4- n -nonylphenol...
11 CitationsSource
#1P.R.B. Silva (UMN: University of Minnesota)H-Index: 11
#2Wanda J Weber (UMN: University of Minnesota)H-Index: 13
Last. Ricardo C. Chebel (UF: University of Florida)H-Index: 30
view all 6 authors...
Objectives of this experiment were to evaluate the effects of recombinant bovine somatotropin (rbST) treatment of periparturient dairy cows on hepatic mRNA expression for genes related to the somatotropic axis, insulin, glucose, and lipid metabolism, inflammation, and oxidative stress. Holstein cows were enrolled in the experiment at 253 ± 3 d of gestation and assigned to 1 of 3 treatments: untreated control (n = 53), 87.5 mg of rbST (n = 56; rbST87.5), and 125 mg of rbST (n = 57; rbST125). Cows...
6 CitationsSource
#1Kevin C. Corbit (UCSF: University of California, San Francisco)H-Index: 8
Last. Ethan J. WeissH-Index: 17
view all 11 authors...
: For nearly 100 years, growth hormone (GH) has been known to affect insulin sensitivity and risk of diabetes. However, the tissue governing the effects of GH signaling on insulin and glucose homeostasis remains unknown. Excess GH reduces fat mass and insulin sensitivity. Conversely, GH insensitivity (GHI) is associated with increased adiposity, augmented insulin sensitivity, and protection from diabetes. Here, we induce adipocyte-specific GHI through conditional deletion of Jak2 (JAK2A), an obl...
24 CitationsSource
#1M.R. Sheehy (UCD: University College Dublin)H-Index: 2
#2Alan G. Fahey (UCD: University College Dublin)H-Index: 21
Last. Finbar Mulligan (UCD: University College Dublin)H-Index: 15
view all 6 authors...
Abstract Body condition score (BCS) change is an indirect measure of energy balance. Energy balance before calving may affect production and health in the following lactation. It is likely that cows may experience BCS loss before calving due to negative energy balance. The objective of this study was to determine if loss of BCS 15d before calving affected milk production, BCS profile, and metabolic status during the transition period and early lactation. On d −15 to d 0 relative to calving, BCS ...
16 CitationsSource
: The aim was to establish a cell culture of adult primary bovine hepatocytes obtained from liver following slaughter and to cultivate the cells in a sandwich culture. Cells and medium samples were taken after separation of cells (day 0), during monolayer (days 1, 2 and 3) and during sandwich culture (days 1, 2, 3, 4, 7, 10 and 14). The mRNA expression of BAX, BCL2L, FAS, IGF-1 and GHR1A was measured as well as urea and LDH. Hepatocytes were obtained by using a two-step collagenase perfusion and...
9 CitationsSource
#1Meric Erikci Ertunc (Harvard University)H-Index: 3
#2Gökhan S. Hotamisligil (Harvard University)H-Index: 111
: Lipids encompass a wide variety of molecules such as fatty acids, sterols, phospholipids, and triglycerides. These molecules represent a highly efficient energy resource and can act as structural elements of membranes or as signaling molecules that regulate metabolic homeostasis through many mechanisms. Cells possess an integrated set of response systems to adapt to stresses such as those imposed by nutrient fluctuations during feeding-fasting cycles. While lipids are pivotal for these homeost...
220 CitationsSource
#1M. L. Douglas (University of Melbourne)H-Index: 6
#2Leah C. MarettH-Index: 17
Last. Martin J. AuldistH-Index: 29
view all 7 authors...
Abstract A positive association between milk protein concentration (MPC) and reproductive performance in dairy cows has been shown in several studies globally. This association may positively influence farm productivity and profitability, particularly in seasonally calving, pasture-based herds. However, the differences in milk production and energy allocation, physical characteristics, and blood plasma nutrient status between cows with differing MPC have not been examined, and the underlying mec...
6 CitationsSource
#1Yuxiang Song (JLU: Jilin University)H-Index: 8
#2Na Li (JLU: Jilin University)H-Index: 2
Last. Guowen Liu (JLU: Jilin University)H-Index: 27
view all 11 authors...
Abstract β-Hydroxybutyrate (BHB) is an important indicator for metabolic disorders in dairy cows, such as ketosis and fatty liver. Dairy cows with ketosis display oxidative stress that may be associated with high levels of BHB. The purpose of this study was to demonstrate a correlation between the high levels of BHB and oxidative stress in dairy cows with ketosis, and to investigate the molecular mechanisms underlying oxidative damage in bovine hepatocytes. The results showed that dairy cows wit...
109 CitationsSource
Cited By51
Newest
#1Fanghui ChenH-Index: 2
#2Le ShengH-Index: 1
Last. Yafei Cai (NAU: Nanjing Agricultural University)H-Index: 4
view all 7 authors...
Source
#1Fan Minghe (JLU: Jilin University)
#2Xiliang Du (JLU: Jilin University)H-Index: 12
Last. Wenwen Gao (JLU: Jilin University)H-Index: 5
view all 16 authors...
ABSTRACT Dairy cows with ketosis exhibit signs of pronounced adipose tissue lipolysis and systemic inflammation, both of which exacerbate this metabolic disorder. In nonruminants, CIDEC plays a pivotal role in the formation of large unilocular lipid droplets. The present study aimed to ascertain the role of CIDEC in the lipolytic and inflammatory response of white adipose tissue (WAT) in vivo and in vitro. Subcutaneous adipose tissue and blood samples were collected from 15 healthy cows (blood β...
Source
Aiming at multi-degree of freedom of traditional sport movement contour tracing, to improve precision and efficiency of the tracking algorithm, a kind of sport movement parameter adaptive Bayes tra...
Source
#1Taiyu Shen (JLU: Jilin University)H-Index: 5
#2Feng Xu (JLU: Jilin University)H-Index: 1
Last. Guowen Liu (JLU: Jilin University)H-Index: 27
view all 17 authors...
ABSTRACT Severe negative energy balance around parturition is an important contributor to ketosis, a metabolic disorder that occurs most frequently in the peripartal period. Autophagy and mitophagy are important processes responsible for breaking down useless or toxic cellular material, and in particular damaged mitochondria. However, the role of autophagy and mitophagy during the occurrence and development of ketosis is unclear. The objective of this study was to investigate autophagy and mitop...
Source
#1Xudong SunH-Index: 7
#2Yan TangH-Index: 1
Last. Chuang XuH-Index: 7
view all 12 authors...
ABSTRACT Ketosis is a serious metabolic disorder characterized by systemic and hepatic oxidative stress, inflammation, and apoptosis, as well as reduced milk yield. Because of the paucity of data on mammary responses during ketosis, the aim of this study was to evaluate alterations in oxidative stress, NF-κB signaling, NLRP3 inflammasome, and caspase apoptotic pathways in mammary gland of dairy cows with ketosis. Blood, mammary gland tissue, and milk samples were collected from healthy cows [Con...
1 CitationsSource
#1Zhou-Lin Wu (Sichuan Agricultural University)H-Index: 3
#2Chen Shiyi (Sichuan Agricultural University)H-Index: 14
Last. Songjia Lai (Sichuan Agricultural University)H-Index: 10
view all 6 authors...
Ketosis is a common metabolic disease in dairy cows during early lactation. However, information about the metabolomic and proteomic profiles associated with the incidence and progression of ketosis is still limited. In this study, an integrated metabolomics and proteomics approach was performed on blood serum sampled from cows diagnosed with clinical ketosis (case, ≥ 2.60 mmol/L plasma β-hydroxybutyrate; BHBA) and healthy controls (control, < 1.0 mmol/L BHBA). Samples were taken 2 weeks before ...
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...
1 CitationsSource
#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 ...
1 CitationsSource
#1Xinwei Li (JLU: Jilin University)H-Index: 23
#2Zhen Shi (JLU: Jilin University)H-Index: 10
Last. Guowen Liu (JLU: Jilin University)H-Index: 27
view all 15 authors...
BACKGROUND AND PURPOSE: Identifying safe and effective compounds that target to mitophagy to eliminate impaired mitochondria may be an attractive therapeutic strategy for NAFLD. Here, we investigated the effects of cyanidin-3-O-glucoside (C3G) on NAFLD and the underlying mechanism. EXPERIMENTAL APPROACH: NAFLD was induced by a high-fat diet (HFD) for 16 weeks. C3G was administered during the last 4 weeks. In vivo, recombinant adenoviruses and AAV8 were used for overexpression and knockdown of PT...
10 CitationsSource
#1Jihong Dong (JLU: Jilin University)H-Index: 7
#2Gerd Bobe (Linus Pauling Institute)H-Index: 27
Last. Xinwei Li (JLU: Jilin University)H-Index: 23
view all 10 authors...
ABSTRACT Inflammation is critical in the progression from benign hepatic lipidosis to pathological hepatic steatosis. The objective of this study was to examine the potential role of the outer mitochondrial membrane protein mitofusin 2 (MFN2) in the etiology of hepatic steatosis in dairy cows during early lactation. Using a nested case–control design, we compared blood and liver samples from 10 healthy cows and 10 age-matched cows with moderate fatty liver. Cows with moderate fatty liver had hig...
1 CitationsSource