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.

The birth of experimental neurosurgery: Wilder Penfield at Montreal’s Royal Victoria Hospital, 1928–1934

2021 ◽  
pp. 1-8
Author(s):  
Richard Leblanc
Keyword(s):  
Royal Victoria Hospital ◽  
Focal Epilepsy ◽  
Spinal Nerve ◽  
Scientific Discipline ◽  
Posttraumatic Epilepsy ◽  
Health And Disease ◽  
Function Relationship ◽  
Del Rio ◽  
Relationship Of ◽  
The Brain

Wilder Penfield is well known as the founder of the Montreal Neurological Institute (MNI), the site of his most important contributions to the investigation and treatment of epilepsy and to our understanding of the structure-function relationship of the brain. The seeds of the MNI were sown 6 years before its opening in 1934, when Penfield accepted the position of head of the Subdepartment of Neurosurgery at McGill University’s Royal Victoria Hospital (RVH). Penfield took this position because of the facilities made available to him to pursue the neuropathological research that he had undertaken with Pío del Río Hortega in Madrid, and to continue his investigation into the nature and treatment of posttraumatic epilepsy that he began with Otfrid Foerster in Breslau. Penfield and his first neurosurgical research fellows Joseph Evans, Jerzy Choróbski, Nathan Norcross, Theodore Erickson, Isadore Tarlov, and Arne Torkildsen studied the substrate of focal epilepsy, the innervation of cortical arteries, the function of the diencephalon, the microscopic structure of spinal nerve roots, and the ventricular system in health and disease. In his 6 years at the RVH, Penfield and his fellows effected a paradigm shift that saw neurosurgery pass from empirical practice to scientific discipline.

scholarly journals Playing Jekyll and Hyde—The Dual Role of Lipids in Fatty Liver Disease

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2244
Author(s):  
Martijn R. Molenaar ◽  
Louis C. Penning ◽  
J. Bernd Helms
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Hepatic Fibrosis ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Stellate Cells ◽  
Alcoholic Fatty Liver ◽  
Hepatic Lipid Accumulation

Lipids play Jekyll and Hyde in the liver. On the one hand, the lipid-laden status of hepatic stellate cells is a hallmark of healthy liver. On the other hand, the opposite is true for lipid-laden hepatocytes—they obstruct liver function. Neglected lipid accumulation in hepatocytes can progress into hepatic fibrosis, a condition induced by the activation of stellate cells. In their resting state, these cells store substantial quantities of fat-soluble vitamin A (retinyl esters) in large lipid droplets. During activation, these lipid organelles are gradually degraded. Hence, treatment of fatty liver disease is treading a tightrope—unsophisticated targeting of hepatic lipid accumulation might trigger problematic side effects on stellate cells. Therefore, it is of great importance to gain more insight into the highly dynamic lipid metabolism of hepatocytes and stellate cells in both quiescent and activated states. In this review, part of the special issue entitled “Cellular and Molecular Mechanisms underlying the Pathogenesis of Hepatic Fibrosis 2020”, we discuss current and highly versatile aspects of neutral lipid metabolism in the pathogenesis of non-alcoholic fatty liver disease (NAFLD).

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 New Insights on Structure and Function of Sialyltransferases

2014 ◽  
Vol 70 (a1) ◽  
pp. C482-C482
Author(s):  
Gesa Volkers ◽  
Liam Worrall ◽  
Emilie Lameignere ◽  
Natalie Strynadka
Keyword(s):  
Sialic Acid ◽  
Schwann Cells ◽  
Molecular Mechanisms ◽  
Neuronal Development ◽  
X Ray Crystallography ◽  
Mechanism Of Catalysis ◽  
Function Relationship ◽  
And Function ◽  
Relationship Of

Sialic acids are a unique posttranslational modification at the terminus of glycoproteins and -lipids. Proteins modified with oligomers of sialic acid add a repellent charge to cell surfaces, which is a crucial feature in cell migration and axonal growth during early brain development. Varied expression levels of sialic acid are linked to tumor malignancy in neuroblastoma, schizophrenia, autism and bipolar disorder but the lack thereof is linked to impaired neuronal development. On the other hand, overexpression of sialic acid oligomers in Schwann cells promotes the peripheral regeneration of lesioned nerves and improves the ability of Schwann cells to migrate into damaged tissue and to remyelinate central nervous system axons. In order to understand the molecular mechanisms of sialylation, our project focuses on the structural characterization of enzymes of the mammalian and bacterial glycosyltransferase families 29 and 42. The proteins of interest were expressed in insect cells and structural studies were undertaken by x-ray crystallography. Kinetics, SEC MALS and glycan array data will shed light on mechanism of catalysis and acceptor specificity. Altogether, the results of this study will promote further understanding of the structure-function relationship of sialyltransferases.

scholarly journals Sasa quelpaertensis Leaf Extract Ameliorates Dyslipidemia, Insulin Resistance, and Hepatic Lipid Accumulation in High-Fructose-Diet-Fed Rats

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3762
Author(s):  
Jeong Yong Park ◽  
Mi Gyeong Jang ◽  
Jung Min Oh ◽  
Hee Chul Ko ◽  
Sung-Pyo Hur ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Signaling Pathway ◽  
Lipid Accumulation ◽  
Leaf Extract ◽  
Metabolic Disorders ◽  
Metabolic Dysfunction ◽  
Hepatic Lipid ◽  
High Fructose Diet ◽  
Hepatic Lipid Accumulation ◽  
High Fructose

Background: Increased dietary fructose consumption is closely associated with lipid and glucose metabolic disorders. Sasa quelpaertensis Nakai possesses various health-promoting properties, but there has been no research on its protective effect against fructose-induced metabolic dysfunction. In this study, we investigated the effects of S. quelpaertensis leaf extract (SQE) on metabolic dysfunction in high-fructose-diet-fed rats. Methods: Animals were fed a 46% carbohydrate diet, a 60% high-fructose diet, or a 60% high-fructose diet with SQE (500 mg/kg of body weight (BW)/day) in drinking water for 16 weeks. Serum biochemical parameters were measured and the effects of SQE on hepatic histology, protein expression, and transcriptome profiles were investigated. Results: SQE improved dyslipidemia and insulin resistance induced in high-fructose-diet-fed rats. SQE ameliorated the lipid accumulation and inflammatory response in liver tissues by modulating the expressions of key proteins related to lipid metabolism and antioxidant response. SQE significantly enriched the genes related to the metabolic pathway, namely, the tumor necrosis factor (TNF) signaling pathway and the PI3K-Akt signaling pathway. Conclusions: SQE could effectively prevent dyslipidemia, insulin resistance, and hepatic lipid accumulation by regulation of metabolism-related gene expressions, suggesting its role as a functional ingredient to prevent lifestyle-related metabolic disorders.

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

scholarly journals Adipose Triglyceride Lipase is needed for homeostatic control of Sterol Element-Binding Protein-1c driven hepatic lipogenesis

2020 ◽  
Author(s):  
Beatrix Irene Wieser ◽  
Paola Peña de la Sancha ◽  
Silvia Schauer ◽  
Helga Reicher ◽  
Wolfgang Sattler ◽  
...  
Keyword(s):  
Binding Protein ◽  
Regulatory Element ◽  
Adipose Triglyceride Lipase ◽  
Proteolytic Activation ◽  
Triglyceride Lipase ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Adipose Tissue Lipolysis ◽  
Rate Limiting

AbstractSterol Regulatory Element-Binding Protein-1c (SREBP-1c) is translated as an inactive precursor-protein that is proteolytically activated to promote fatty-acid (FA) biosynthesis, when unsaturated (u)FAs are scarce. During fasting, however, lipogenesis is low, and adipose-tissue lipolysis supplies the organism with FAs. Adipose TriGlyceride Lipase (ATGL) is the rate-limiting enzyme for lipolysis, and it preferentially hydrolyzes uFAs. Therefore, we hypothesized that ATGL-derived FAs may suppress the proteolytic activation of SREBP-1c in the liver. Here we show that (i) SREBP-1c is inactive during fasting but active after refeeding, (ii) uFA species liberated by ATGL suppress SREBP-1c activation in vitro, (iii) SREBP-1c is hyper-activated in livers of mice lacking ATGL, and (iv) pharmacological inhibition of ATGL selectively activates SREBP-1c in hepatocytes. Our findings highlight an ATGL/SREBP-1c axis, instrumental to coordinate lipogenesis and lipolysis, whose homeostatic regulation is crucial to avoid severe diseases including diabetes, cardiomyopathy, and even cancer.

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