BHBA Influences Bovine Hepatic Lipid Metabolism via AMPK Signaling Pathway

Published on Jun 1, 2015in Journal of Cellular Biochemistry4.237
· DOI :10.1002/JCB.25062
β-hydroxybutyric acid (BHBA), an important metabolite in β-oxidation, is involved in the development of ketosis in dairy cows. It is known that AMP-activated protein kinase (AMPK) signaling pathway plays an important role in the regulation of lipid metabolism in hepatocytes. In the present study, bovine hepatocytes were treated with BHBA at variable concontrations and Compound C (Cpd C, an AMPK inhibitor) to investigate the effects of BHBA on the AMPK signaling pathway. The results showed that when the concentration of BHBA reached 1.2 mM, the AMPK signaling pathway was activated and the expression of sterol regulatory element binding protein-1c (SREBP-1c) as well as its target genes were significantly decreased. And these decreases were blocked by Cpd C. The binding activity and nucleus translocation of SREBP-1c showed a similar trend. The expression of peroxisome proliferator activated receptor-α (PPARα), carbohydrates response element binding protein (ChREBP) and their target genes were significantly increased while they were negatively suppressed by the Cpd C. The content of triglyceride (TG) had no obviously change in the BHBA and Cpd C-treated groups. These results indicate that BHBA can activate AMPK signaling pathway and regulate lipid synthesis and lipid oxidation genes of AMPK but showed no effect on TG in bovine hepatocytes. J. Cell. Biochem. 116: 1070–1079, 2015. © 2015 Wiley Periodicals, Inc.
📖 Papers frequently viewed together
5 Citations
20132.74PLOS ONE
9 Authors (Xinwei Li, ..., Zhe Wang)
53 Citations
50 Citations
#1Shih Lung Woo (A&M: Texas A&M University)H-Index: 11
#2Hang Xu (A&M: Texas A&M University)H-Index: 10
Last. Chaodong Wu (A&M: Texas A&M University)H-Index: 33
view all 20 authors...
Non-alcoholic fatty liver disease (NAFLD) is closely associated with obesity and insulin resistance. To better understand the pathophysiology of obesity-associated NAFLD, the present study examined the involvement of liver and adipose tissues in metformin actions on reducing hepatic steatosis and inflammation during obesity. C57BL/6J mice were fed a high-fat diet (HFD) for 12 weeks to induce obesity-associated NAFLD and treated with metformin (150 mg/kg/d) orally for the last four weeks of HFD f...
127 CitationsSource
Background/Aims: s-hydroxybutyrate (BHBA) is the major component of ketone bodies in ketosis. Dairy cows with ketosis often undergo oxidative stress. BHBA is related to the inflammation involved in other diseases of dairy cattle. However, whether BHBA can induce inflammatory injury in dairy cow hepatocytes and the potential mechanism of this induction are not clear. The NF-κB pathway plays a vital role in the inflammatory response. Methods: Therefore, this study evaluated the oxidative stress, p...
59 CitationsSource
#1A. Mahrt (FU: Free University of Berlin)H-Index: 3
#2O. Burfeind (FU: Free University of Berlin)H-Index: 18
Last. Wolfgang Heuwieser (FU: Free University of Berlin)H-Index: 46
view all 3 authors...
Abstract Two trials were conducted to examine factors potentially influencing the measurement of blood β-hydroxybutyric acid (BHBA) in dairy cows. The objective of the first trial was to study effects of sampling time on BHBA concentration in continuously fed dairy cows. Furthermore, we determined test characteristics of a single BHBA measurement at a random time of the day to diagnose subclinical ketosis considering commonly used cut-points (1.2 and 1.4mmol/L). Finally, we set out to evaluate i...
21 CitationsSource
#1Seoyoon Choi (Yonsei University)H-Index: 2
#2Youngshim Choi (Yonsei University)H-Index: 18
Last. Taesun Park (Yonsei University)H-Index: 32
view all 6 authors...
This study examined the effect of piperine on hepatic steatosis and insulin resistance induced in mice by feeding a high-fat diet (HFD) for 13 weeks and elucidated potential underlying molecular mechanisms. Administration of piperine (50 mg/kg body weight) to mice with HFD-induced hepatic steatosis resulted in a significant increase in plasma adiponectin levels. Also, elevated plasma concentrations of insulin and glucose and hepatic lipid levels induced by feeding a HFD were reversed in mice whe...
57 CitationsSource
#1Chongming WuH-Index: 15
#2Hong LuanH-Index: 2
Last. Xi Chen (Peking Union Medical College)H-Index: 8
view all 8 authors...
Sophoricoside, an isoflavone glycoside isolated from Sophora japonica (Leguminosae), has been widely reported as an immunomodulator. In this study, the effects of sophoricoside on lipogenesis and glucose consumption in HepG2 cells and C2C12 myotubes were investigated. Treatment with sophoricoside at concentrations of 1–10 μM inhibited lipid accumulation in HepG2 cells in a dose-dependent manner. At the same concentration range, no effect on cell viability was observed in the MTT assay. Inhibitio...
24 CitationsSource
#1Lei Liu (CQMU: Chongqing Medical University)H-Index: 1
#2Ming Yang (CQMU: Chongqing Medical University)H-Index: 2
Last. Yuhao LiH-Index: 34
view all 9 authors...
Abstract Ethnopharmacological relevance Salacia oblonga root (SOR) is a traditionally herbal medicine for obesity and diabetes, which are closely associated with fatty liver. To investigate the molecular mechanisms of SOR in the treatment of dietary-induced fatty liver. Materials and methods Male rats were co-administered with fructose in drinking water and vehicle or the aqueous-ethanolic extract of SOR (by gavage, once daily) for 10 weeks. Biochemical variables were determined enzymatically or...
17 CitationsSource
#1Michael Iwersen (University of Veterinary Medicine Vienna)H-Index: 17
#2D. Klein-Jöbstl (University of Veterinary Medicine Vienna)H-Index: 9
Last. Marc Drillich (University of Veterinary Medicine Vienna)H-Index: 31
view all 7 authors...
The objective of this study was to determine the suitability of 2 electronic hand-held devices [FreeStyle Precision (FSP), Abbott GmbH & Co. KG, Wiesbaden, Germany and GlucoMen LX Plus (GLX), A. Menarini GmbH, Vienna, Austria] for measuring β-hydroxybutyrate (BHBA) in dairy cows. Three experiments were conducted to evaluate (1) the diagnostic performance of the devices, (2) the effect of the type of blood sample, and (3) the influence of the ambient temperature on the determined results. A total...
55 CitationsSource
#1Xinwei Li (JLU: Jilin University)H-Index: 23
#2Hui Chen (JLU: Jilin University)H-Index: 93
Last. Zhe Wang (JLU: Jilin University)H-Index: 26
view all 9 authors...
The effect of acetic acid on hepatic lipid metabolism in ruminants differs significantly from that in monogastric animals. Therefore, the aim of this study was to investigate the regulation mechanism of acetic acid on the hepatic lipid metabolism in dairy cows. The AMP-activated protein kinase (AMPK) signaling pathway plays a key role in regulating hepatic lipid metabolism. In vitro, bovine hepatocytes were cultured and treated with different concentrations of sodium acetate (neutralized acetic ...
53 CitationsSource
#1Hai Yan Quan (Kyung Hee University)H-Index: 8
#2Do Yeon KimH-Index: 11
Last. Sung Hyun Chung (Kyung Hee University)H-Index: 18
view all 3 authors...
The main purpose of this study is to examine the effect of caffeine on lipid accumulation in human hepatoma HepG2 cells. Significant decreases in the accumulation of hepatic lipids, such as triglyceride (TG), and cholesterol were observed when HepG2 cells were treated with caffeine as indicated. Caffeine decreased the mRNA level of lipogenesis-associated genes (SREBP1c, SREBP2, FAS, SCD1, HMGR and LDLR). In contrast, mRNA level of CD36, which is responsible for lipid uptake and catabolism, was i...
34 CitationsSource
#1Thomas Laeger (Leibniz Association)H-Index: 15
#2Ralf PöhlandH-Index: 1
Last. Björn KuhlaH-Index: 15
view all 4 authors...
b-Hydroxybutyric acid (BHBA) acts in the brain to influence feeding behaviour, but the underlying molecular mechanisms are unclear. GT1-7 hypothalamic cells expressing orexigenic agouti-related peptide (AGRP) were used to study the AMPactivated protein kinase (AMPK) pathway known to integrate dietary and hormonal signals for food intake regulation. In a 25 mM glucose culture medium, BHBA increased intracellular calcium concentrations and the expression of monocarboxylate transporter 1 (MCT1 (SLC...
25 CitationsSource
Cited By21
#1Lin Lei (JLU: Jilin University)H-Index: 6
#2Wenwen Gao (JLU: Jilin University)H-Index: 5
Last. Xinwei Li (JLU: Jilin University)H-Index: 23
view all 10 authors...
Ketotic dairy cows exhibit a state of negative energy balance (NEB) characterized by elevated circulating levels of β-hydroxybutyrate (BHB) and fatty acids. Impaired hepatic insulin signaling in dairy cows occurs frequently during the transition into lactation, but its role on liver function during this period is not well known. In nonruminants, endoplasmic reticulum (ER) stress is a causal factor contributing to impaired insulin signaling in the liver. Thus, the aim of this study was to investi...
#1Juliana G. Ferst (UFSM: Universidade Federal de Santa Maria)
#2Werner G. Glanzner (McGill University)H-Index: 12
Last. Vilceu Bordignon (McGill University)H-Index: 24
view all 9 authors...
ABSTRACT null null There is growing evidence that greater than homeostatic blood concentrations of nonesterified fatty acids (NEFAs) and β-hydroxybutyrate (BHBA) have negative consequences on dairy cow’s fertility, but effects on cell homeostasis in the reproductive system is not completely understood. In this study, lipids accumulation, reactive oxygen species (ROS) concentrations, abundance of gene transcripts, and immunofluorescence signal of H3K4me3 and H3K9me3 were evaluated in endometrial ...
#1Tianle Xu (YZU: Yangzhou University)H-Index: 10
#2Xubin Lu (YZU: Yangzhou University)H-Index: 5
Last. Zhangping Yang (YZU: Yangzhou University)H-Index: 10
view all 7 authors...
The occurrence of bovine ketosis involves the accumulation of β-hydroxybutyric acid (BHBA), which contributes to the initiation and acceleration of hepatic metabolic stress and inflammation. Metformin has other beneficial effects apart from its medical intervention for diabetes, such as prevention of laminitis and hyper-triglyceridemic. AMPK maintains energy homeostasis and is the intracellular target of metformin action. This study aims to uncover the role of metformin in modulating BHBA-induce...
#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...
#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...
#1Yanfei Yang (Academy of Medical Sciences, United Kingdom)
#2Yabin Li (Academy of Medical Sciences, United Kingdom)
Last. Yanfen Wang (Academy of Medical Sciences, United Kingdom)
view all 4 authors...
Gastrodin has shown the potential as an anticonvulsant. Epilepsy is a neurological disease with significant effects in children. In the current study, the therapeutic potential of gastrodin in handling pediatric epilepsy was explored by focusing on the AMPK/PPARα pathway. Three-week-old Sprague-Dawley rats were subjected to lithium-pilocarpine method to induce epileptic symptoms and then administrated with gastrodin. The effects of gastrodin on rats were first assessed using electroencephalogram...
#1M. Garcia-Roche (University of the Republic)H-Index: 3
#2Guillermo Cañibe (University of the Republic)
Last. Mariana Carriquiry (University of the Republic)H-Index: 13
view all 9 authors...
In this study we explored mechanisms related to glucose and fatty acid metabolism in Holstein-Friesian multiparous dairy cows during lactation under two feeding strategies. From 0 to 180 days postpartum, cows were fed total mixed ration ad libitum (non-grazing group, G0) or grazed Festuca arundinacea or Medicago sativa and were supplemented with 5.4 kg DM/d of an energy-protein concentrate (grazing group, G1). From 180 to 250 days postpartum, all cows grazed Festuca arundinacea and were suppleme...
#1Chang ZhaoH-Index: 2
#2Yunlong BaiH-Index: 3
Last. Chuang XuH-Index: 2
view all 6 authors...
Inactive ovaries (IO) affect the estrus cycle and timed artificial insemination (TAI) efficiency in dairy cows during early lactation. The objective of the experiment was to determine metabolic changes in serum and milk whey of dairy cows with IO and estrus. Twenty-eight healthy postpartum Holstein cows in similar age, milk production, and body condition were selected at 30 d postpartum for tracking to 70 d postpartum and estrus performance was recorded through Afi Farm® software. The ovarian st...
#1Jing Shen (NWAFU: Northwest A&F University)H-Index: 26
#2Xiaoying Han (NWAFU: Northwest A&F University)H-Index: 3
Last. Junhu Yao (NWAFU: Northwest A&F University)H-Index: 9
view all 9 authors...
BACKGROUND High rumen-degradable starch (RDS) diets decrease milk fat. The increase of LPS in plasma associated with increased RDS impairs liver function, immune response and lipid metabolism, which depress the precursors for milk fat. OBJECTIVE This study investigated the mechanism of depression of milk fat precursors in the liver and small intestine of dairy goats fed different RDS diets. METHOD Eighteen Guanzhong lactating goats (second lactation, 45.8 ± 1.54 kg) and 6 ruminally cannulated da...
2 CitationsSource
#1Jing Shen (NWAFU: Northwest A&F University)H-Index: 26
#2Bo-fei Sun (NWAFU: Northwest A&F University)H-Index: 2
Last. Junhu Yao (NWAFU: Northwest A&F University)H-Index: 9
view all 6 authors...
: High concentrations of nonesterified fatty acids (NEFAs) and β-hydroxybutyric acid (BHBA) induce lipid peroxidation, resulting in liver damage. Choline and methionine (Met) can promote energy balance and benefit liver health in transition dairy cows; however, the regulating mechanism remains unclear. In the present study, we established the hepatocyte damage model by 1.5 mM NEFAs or BHBA treatment, and examined lipid metabolism in hepatocytes. The results showed that 1.5 mM NEFAs and 1.5 mM BH...
5 CitationsSource