Glucagon attenuates lipid accumulation in cow hepatocytes through AMPK signaling pathway activation.

Published on May 1, 2019in Journal of Cellular Physiology5.546
· DOI :10.1002/JCP.27258
Yu Li8
Estimated H-index: 8
(AAU: Anhui Agricultural University),
Hongyan Ding7
Estimated H-index: 7
(AAU: Anhui Agricultural University)
+ 8 AuthorsXinwei Li23
Estimated H-index: 23
(JLU: Jilin University)
Sources
Abstract
: The ketotic cows displayed hepatic lipid metabolic disorder and high blood concentration of glucagon. Importantly, adenosine monophosphate-activated protein kinase (AMPK) signaling pathway plays an important role in the hepatic lipid homeostasis. Therefore, the aim of this study was to investigate the effect of glucagon on AMPK pathway and its underlying mechanism on lipid metabolism in cow hepatocytes. Cow hepatocytes were cultured and treated with glucagon and AMPK inhibitor (BML-275). The results showed that glucagon significantly promoted the expression of glucagon receptor and increased the phosphorylation level and activity of AMPKα. Activated AMPKα increased the expression level and transcriptional activity of peroxisome proliferator-activated receptor α, which further increased the expression of fatty acid oxidation genes and lipid oxidation. Furthermore, activated AMPKα inhibited the expression level and transcriptional activity of sterol regulatory element binding protein-1c and carbohydrate response element binding protein, which decreased the expression of lipogenic genes, thereby decreasing lipid synthesis. In addition, glucagon also increased the expression of very-low-density lipoprotein (VLDL) assembly to export intracellular triglycerides (TG). Consequently, the content of intracellular TG was significantly decreased in cow hepatocytes. These results indicate that glucagon activates the AMPK signaling pathway to increase lipid oxidation and VLDL assembly and decrease lipid synthesis in cow hepatocytes, thereby reducing liver fat accumulation.
📖 Papers frequently viewed together
33 Citations
370 Citations
2011
1 Author (I-Chen Peng)
References33
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
#1Jie Zhou (CPU: China Pharmaceutical University)H-Index: 5
#2Cai Xingguang (CPU: China Pharmaceutical University)H-Index: 7
Last. Hai Qian (CPU: China Pharmaceutical University)H-Index: 22
view all 10 authors...
Abstract Glucagon has plenty of effects via a specific glucagon receptor(GCGR) like elevating the blood glucose, improving fatty acids metabolism, energy expenditure and increasing lipolysis in adipose tissue. The most important role of glucagon is to regulate the blood glucose, but the emergent possibilities of hyperglycaemia is exist. Glucagon could also slightly activate glucagon-like peptide-1 receptor(GLP-1R), which lead to blood glucose lowering effect. This study aims to erase the likelih...
23 CitationsSource
#1Yu Li (AAU: Anhui Agricultural University)H-Index: 11
#2Hongyan Ding (AAU: Anhui Agricultural University)H-Index: 7
Last. Xinwei Li (JLU: Jilin University)H-Index: 23
view all 12 authors...
Elevated levels of blood interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor–α (TNF–α) increase insulin resistance and result in inflammation. It is not clear whether elevated blood level of acetoacetate (ACAC) and decreased blood level of glucose, which are the predominant characteristics of clinical biochemistry in ketotic dairy cows, increase proinflammatory cytokines and subsequent inflammation. The objective of this study was to test the hypothesis that ACAC and glucose ...
12 CitationsSource
The objective of this study was to investigate the measurement of serum fibroblast growth factor-21 (FGF-21), a protein mainly synthesized by the liver, as a sensitive biomarker for diagnosis of ketosis in dairy cows. Ninety Holstein–Friesian dairy cows (60 healthy and 30 ketosis cases) were selected and divided into a Ketosis group (K), and a Control group (C). We measured serum FGF-21 and other biochemical parameters by commercial ELISA kits. In a combined population of all 90 cows, we found t...
11 CitationsSource
#1Chuang XuH-Index: 7
Last. Ziyang ZhangH-Index: 2
view all 9 authors...
Background Negative energy balance (NEB) is a common pathological foundation of ketosis and fatty liver. Liver and fat tissue are the major organs of lipid metabolism and take part in modulating lipid oxidative capacity and energy demands, which is also a key metabolic pathway that regulates NEB develop during perinatal period. Fibroblast growth factor-21 (FGF-21) is a recently discovered protein hormone that plays an important and specific regulating role in adipose lipid metabolism and liver g...
12 CitationsSource
#1Qinghua Deng (JLU: Jilin University)H-Index: 8
#2Guowen Liu (JLU: Jilin University)H-Index: 27
Last. Xinwei Li (JLU: Jilin University)H-Index: 23
view all 16 authors...
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 w...
19 CitationsSource
#1Chuang XuH-Index: 8
#2Shi ShuH-Index: 4
Last. Changsheng LiH-Index: 2
view all 7 authors...
Background: Ketosis is an important metabolic disorder in dairy cows during the transition period. The urine proteomics of ketosis has not been investigated using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS).Objective: The aim is to determine differences between urine proteomic profiles of healthy cows and those with clinical ketosis, and facilitate studies of the underlying physiological and biochemical mechanisms that lead to liver pathology in k...
16 CitationsSource
#1Yuxiang Song (JLU: Jilin University)H-Index: 8
#2Xinwei Li (JLU: Jilin University)H-Index: 23
Last. Zhe Wang (JLU: Jilin University)H-Index: 26
view all 10 authors...
A high plasma concentration of non-esterified fatty acids (NEFAs) is an important pathogenic factor that leads to ketosis and fatty liver in dairy cows. NEFAs may be associated with oxidative stress in dairy cows with ketosis or fatty liver and the subsequent induction of hepatocyte damage. However, the molecular mechanism of NEFAs-induced oxidative stress and whether NEFAs cause apoptosis of hepatocytes are unclear. Therefore, the aim of this study was to investigate the molecular mechanism of ...
55 CitationsSource
#1Lei Liu (JLU: Jilin University)H-Index: 13
#2Xinwei Li (JLU: Jilin University)H-Index: 23
Last. Guowen Liu (JLU: Jilin University)H-Index: 27
view all 13 authors...
Abstract High serum concentrations of nonesterified fatty acids (NEFA), which may affect the synthesis and assembly of very low density lipoproteins (VLDL), are associated with fatty liver during the early lactation period. Therefore, the objective of this study was to investigate the effects of NEFA on the synthesis and assembly of VLDL in bovine hepatocytes. Bovine hepatocytes were cultured and treated with different concentrations of NEFA. The mRNA expression of apolipoprotein B100 ( ApoB100 ...
27 CitationsSource
#1Jialin Xu (NU: Northeastern University)H-Index: 9
#2Ajay C. Donepudi (URI: University of Rhode Island)H-Index: 12
Last. Angela L. Slitt (URI: University of Rhode Island)H-Index: 34
view all 4 authors...
Aims The purpose of this study was to determine whether Nrf2 activation, via Keap1-knockdown (Keap1-KD), regulates lipid metabolism and mobilization induced by food deprivation (e.g. fasting).
34 CitationsSource
Cited By6
Newest
#1Kun Zhang (JXAU: Jiangxi Agricultural University)
#2Yan Shi (JXAU: Jiangxi Agricultural University)H-Index: 2
Last. Xiaoquan Guo (JXAU: Jiangxi Agricultural University)H-Index: 12
view all 12 authors...
The fatty liver hemorrhage syndrome in laying hens is a disease of lipid metabolism disorders. Importantly, energy sensor AMP-activated protein kinase (AMPK) plays an essential role in homeostasis regulation of liver lipid. The current research aims to investigate the relationship between AMPK signaling pathway and lipid metabolism in laying hen hepatocytes and explore the underlying mechanisms. The steatotic hepatocytes model of laying hen was established and treated with AMPK agonist AICAR and...
Source
#1Hongyan Ding (AAU: Anhui Agricultural University)H-Index: 7
#2Yu Li (AAU: Anhui Agricultural University)H-Index: 11
Last. Jinjie Wu (AAU: Anhui Agricultural University)H-Index: 10
view all 11 authors...
Epigallocatechin-3-gallate (EGCG) plays a crucial role in hepatic lipid metabolism. However, the underlying regulatory mechanism of hepatic lipid metabolism by EGCG in canine is unclear. Primary canine hepatocytes were treated with EGCG (0.01, 0.1, or 1 μM) and BML-275 (an AMP-activated protein kinase [AMPK] inhibitor) to study the effects of EGCG on the gene and protein expressions associated with AMPK signaling pathway. Data showed that treatment with EGCG had greater activation of AMPK, as we...
1 CitationsSource
#1Yu Li (AAU: Anhui Agricultural University)H-Index: 8
#2Hongyan Ding (AAU: Anhui Agricultural University)H-Index: 7
Last. Guowen Liu (JLU: Jilin University)H-Index: 27
view all 13 authors...
Elevated plasma nonesterified fatty acid (NEFA) levels and hepatocytes damage are characteristics of ketosis in dairy cows. Oxidative stress is associated with the pathogenesis of NEFA-induced liver damage. However, the exact mechanism by which oxidative stress mediates NEFA-induced hepatocytes apoptosis and liver injury remains poorly understood. The results of the present study demonstrated that NEFA contribute to reactive oxygen species (ROS) generation, resulting in an imbalance between oxid...
9 CitationsSource
#1Murat BaimishevH-Index: 1
#2Sergey EreminH-Index: 1
view all 6 authors...
The purpose of the research is to determine the etiopathogenesis of reproductive dysfunction in highly productive cows. For this, one group of cows was formed on the principle of paranalogs in the amount of 37 animals inseminated in the first sexual hunt after calving, followed by taking blood samples from them using the Monovet system, considering the duration of pregnancy. During the start-up period, blood was taken 1–4 days before calving and on the first day after calving. A total of 253 blo...
Source
#1M. BaimishevH-Index: 1
#2S YereminH-Index: 1
Last. I. KonopeltsevH-Index: 1
view all 5 authors...
2 CitationsSource
#1Xiangnan Zhang (SNNU: Shaanxi Normal University)H-Index: 3
#2Qiu Wu (SNNU: Shaanxi Normal University)H-Index: 3
Last. Xingbin Yang (SNNU: Shaanxi Normal University)H-Index: 38
view all 5 authors...
Emerging evidence supports the health-promoting ability of a special microbial-fermented Fuzhuan brick tea. Epigallocatechin gallate was identified as a dominant flavonoid of Fuzhuan tea aqueous extract (FTE). Mice were treated with 30% high fructose (HF) water feeding alone or in combination with administration of FTE at 400 mg per kg bw for 13 weeks. FTE caused strong inhibition against the elevation of liver weight, serum enzymatic (aspartate aminotransferase, aspartate aminotransferase and a...
5 CitationsSource