scholarly journals Myocardial Adipose Triglyceride Lipase Overexpression Protects against Burn-Induced Cardiac Lipid Accumulation and Injury

2019 ◽  
Vol 2019 ◽  
pp. 1-16
Author(s):  
Lingfei Li ◽  
Xingyue Zhang ◽  
Qiong Zhang ◽  
Jiezhi Jia ◽  
Junhui Zhang ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
Glucose Transporter ◽  
Glucose Utilization ◽  
Burn Injury ◽  
Therapeutic Potential ◽  
Cardiac Injury ◽  
Adipose Triglyceride Lipase ◽  
Glucose Transporter 1 ◽  
Cardiac Lipid ◽  
Triglyceride Lipase

Maladaptive cardiac metabolism is a common trigger of cardiac lipid accumulation and cardiac injury under serious burn challenge. Adipose triglyceride lipase (ATGL) is the key enzyme that catalyzes triglyceride hydrolysis; however, its alteration and impact on cardiac function following serious burn injury are still unknown. Here, we found that the cardiac fatty acid (FA) metabolism increased, accompanied by augmented FA accumulation and ATGL expression, after serious burn injury. We generated heterozygous ATGL knockout and heterozygous cardiac-specific ATGL overexpression thermal burn mice. The results demonstrated that partial loss of ATGL could not relieve burn-induced cardiac lipid accumulation and cardiac injury, possibly due to the suppression of cardiac FA metabolism plus insufficient compensatory glucose utilization. In contrast, cardiac-specific overexpression of ATGL alleviated cardiac lipid accumulation and cardiac injury following burn challenge by switching the substrate preference from FA towards increased glucose utilization. The underlying mechanism was possibly related to increased glucose transporter-1 expression and reduced cardiac lipid accumulation induced by ATGL overexpression. Our data first demonstrated that elevated cardiac ATGL expression after serious burn injury is an adaptive, albeit insufficient, response to compensate for the increase in energy consumption and that further overexpression of ATGL is beneficial for ameliorating cardiac injury, indicating its therapeutic potential.

scholarly journals Adipose Triglyceride Lipase in Hepatic Physiology and Pathophysiology

Biomolecules ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 57
Author(s):  
Tianjiao Li ◽  
Wei Guo ◽  
Zhanxiang Zhou
Keyword(s):  
Lipid Accumulation ◽  
Metabolic Disorders ◽  
Molecular Mechanisms ◽  
Adipose Triglyceride Lipase ◽  
Triglyceride Lipase ◽  
Hepatic Lipid Accumulation ◽  
Health And Disease ◽  
Function Relationship ◽  
Relationship Of ◽  
Rate Limiting

The liver is extremely active in oxidizing triglycerides (TG) for energy production. An imbalance between TG synthesis and hydrolysis leads to metabolic disorders in the liver, including excessive lipid accumulation, oxidative stress, and ultimately liver damage. Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme that catalyzes the first step of TG breakdown to glycerol and fatty acids. Although its role in controlling lipid homeostasis has been relatively well-studied in the adipose tissue, heart, and skeletal muscle, it remains largely unknown how and to what extent ATGL is regulated in the liver, responds to stimuli and regulators, and mediates disease progression. Therefore, in this review, we describe the current understanding of the structure–function relationship of ATGL, the molecular mechanisms of ATGL regulation at translational and post-translational levels, and—most importantly—its role in lipid and glucose homeostasis in health and disease with a focus on the liver. Advances in understanding the molecular mechanisms underlying hepatic lipid accumulation are crucial to the development of targeted therapies for treating hepatic metabolic disorders.

Construction and Identification of an Antisense Glucose Transporter-1 Plasmid

2008 ◽  
Vol 36 (5) ◽  
pp. 1001-1007
Author(s):  
XM Chen ◽  
SH Zhou ◽  
J Fan ◽  
MJ Hu ◽  
SQ Wang ◽  
...  
Keyword(s):  
Laryngeal Carcinoma ◽  
Glucose Transporter ◽  
Therapeutic Potential ◽  
Restriction Analysis ◽  
Expression System ◽  
Carcinoma Cells ◽  
Glucose Transporter 1 ◽  
Glut 1 ◽  
Firm Basis ◽  
Polymerase Chain

Our aim was to construct a pcDNA3.1(+) eucaryotic expression system vector containing the antisense glucose transporter-1 ( Glut-1) gene. Total RNA was isolated from human Hep-2 laryngeal carcinoma cells, and the Glut-1 and antisense Glut-1 sequences were amplified by polymerase chain reaction. Expression plasmids containing the sense and antisense cDNA were constructed using the pcDNA3.1(+) vector. The resulting sense and antisense vectors, pcDNA3.1(+)-Glut-1 and pcDNA3.1(+)-antiGlut-1, respectively, were examined by restriction analysis and DNA sequencing. The pcDNA3.1(+)-antiGlut-1 was subsequently transfected into Hep-2 cells. Anti Glut-1 mRNA expression was detected, indicating the successful construction of an antisense Glut-1 plasmid capable of transfecting Hep-2 laryngeal carcinoma cells. These data provide a firm basis for additional studies using the plasmid pcDNA3.1(+)-antiGlut-1 to determine its therapeutic potential for the treatment of laryngeal carcinoma.

scholarly journals Downregulation of adipose triglyceride lipase by EB viral‐encoded LMP2A links lipid accumulation to increased migration in nasopharyngeal carcinoma

2020 ◽  
Vol 14 (12) ◽  
pp. 3234-3252
Author(s):  
Shixing Zheng ◽  
Liudmila Matskova ◽  
Xiaoying Zhou ◽  
Xue Xiao ◽  
Guangwu Huang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Lipid Accumulation ◽  
Adipose Triglyceride Lipase ◽  
Triglyceride Lipase

HIF1-α-Mediated Gene Expression Induced by Vitamin B1 Deficiency

2013 ◽  
Vol 83 (3) ◽  
pp. 188-197 ◽  
Author(s):  
Rebecca L. Sweet ◽  
Jason A. Zastre
Keyword(s):  
Gene Expression ◽  
Thiamine Deficiency ◽  
Glucose Transporter ◽  
Neuroblastoma Cell ◽  
Hypoxia Inducible Factor ◽  
Clinical Manifestations ◽  
Vitamin B1 ◽  
Low Oxygen ◽  
Glucose Transporter 1 ◽  
Metabolic Intermediates

It is well established that thiamine deficiency results in an excess of metabolic intermediates such as lactate and pyruvate, which is likely due to insufficient levels of cofactor for the function of thiamine-dependent enzymes. When in excess, both pyruvate and lactate can increase the stabilization of the hypoxia-inducible factor 1-alpha (HIF-1α) transcription factor, resulting in the trans-activation of HIF-1α regulated genes independent of low oxygen, termed pseudo-hypoxia. Therefore, the resulting dysfunction in cellular metabolism and accumulation of pyruvate and lactate during thiamine deficiency may facilitate a pseudo-hypoxic state. In order to investigate the possibility of a transcriptional relationship between hypoxia and thiamine deficiency, we measured alterations in metabolic intermediates, HIF-1α stabilization, and gene expression. We found an increase in intracellular pyruvate and extracellular lactate levels after thiamine deficiency exposure to the neuroblastoma cell line SK-N-BE. Similar to cells exposed to hypoxia, there was a corresponding increase in HIF-1α stabilization and activation of target gene expression during thiamine deficiency, including glucose transporter-1 (GLUT1), vascular endothelial growth factor (VEGF), and aldolase A. Both hypoxia and thiamine deficiency exposure resulted in an increase in the expression of the thiamine transporter SLC19A3. These results indicate thiamine deficiency induces HIF-1α-mediated gene expression similar to that observed in hypoxic stress, and may provide evidence for a central transcriptional response associated with the clinical manifestations of thiamine deficiency.

Glycolysis Inhibition as a Strategy for Hepatocellular Carcinoma Treatment?

2018 ◽  
Vol 19 (1) ◽  
pp. 26-40 ◽  
Author(s):  
A.P. Alves ◽  
A.C. Mamede ◽  
M.G. Alves ◽  
P.F. Oliveira ◽  
S.M. Rocha ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Glucose Transporter ◽  
Public Health Problem ◽  
High Morbidity ◽  
Curative Intent ◽  
Malignant Liver Tumor ◽  
Glucose Transporter 1 ◽  
Inhibition Of Glycolysis

Hepatocellular carcinoma (HCC) is the most frequently detected primary malignant liver tumor, representing a worldwide public health problem due to its high morbidity and mortality rates. The HCC is commonly detected in advanced stage, precluding the use of treatments with curative intent. For this reason, it is crucial to find effective therapies for HCC. Cancer cells have a high dependence of glycolysis for ATP production, especially under hypoxic environment. Such dependence provides a reliable possible strategy to specifically target cancer cells based on the inhibition of glycolysis. HCC, such as other cancer types, presents a clinically well-known upregulation of several glycolytic key enzymes and proteins, including glucose transporters particularly glucose transporter 1 (GLUT1). Such enzymes and proteins constitute potential targets for therapy. Indeed, for some of these targets, several inhibitors were already reported, such as 2-Deoxyglucose, Imatinib or Flavonoids. Although the inhibition of glycolysis presents a great potential for an anticancer therapy, the development of glycolytic inhibitors as a new class of anticancer agents needs to be more explored. Herein, we propose to summarize, discuss and present an overview on the different approaches to inhibit the glycolytic metabolism in cancer cells, which may be very effective in the treatment of HCC.

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