scholarly journals Metabolomic Profiling Reveals a Role for Caspase-2 in Lipoapoptosis

2013 ◽  
Vol 288 (20) ◽  
pp. 14463-14475 ◽  
Author(s):  
Erika Segear Johnson ◽  
Kelly R. Lindblom ◽  
Alexander Robeson ◽  
Robert D. Stevens ◽  
Olga R. Ilkayeva ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Metabolic Diseases ◽  
Response To Treatment ◽  
Alcoholic Fatty Liver ◽  
Metabolomic Profiling ◽  
Egg Extracts ◽  
Attractive Therapeutic Target ◽  
Caspase 2 ◽  
Induced Apoptosis ◽  
Alcoholic Fatty Liver Disease

The accumulation of long-chain fatty acids (LCFAs) in non-adipose tissues results in lipid-induced cytotoxicity (or lipoapoptosis). Lipoapoptosis has been proposed to play an important role in the pathogenesis of several metabolic diseases, including non-alcoholic fatty liver disease, diabetes mellitus, and cardiovascular disease. In this report, we demonstrate a novel role for caspase-2 as an initiator of lipoapoptosis. Using a metabolomics approach, we discovered that the activation of caspase-2, the initiator of apoptosis in Xenopus egg extracts, is associated with an accumulation of LCFA metabolites. Metabolic treatments that blocked the buildup of LCFAs potently inhibited caspase-2 activation, whereas adding back an LCFA in this scenario restored caspase activation. Extending these findings to mammalian cells, we show that caspase-2 was engaged and activated in response to treatment with the saturated LCFA palmitate. Down-regulation of caspase-2 significantly impaired cell death induced by saturated LCFAs, suggesting that caspase-2 plays a pivotal role in lipid-induced cytotoxicity. Together, these findings reveal a previously unknown role for caspase-2 as an initiator caspase in lipoapoptosis and suggest that caspase-2 may be an attractive therapeutic target for inhibiting pathological lipid-induced apoptosis.

scholarly journals A Narrative Review on the Role of AMPK on De Novo Lipogenesis in Non-Alcoholic Fatty Liver Disease: Evidence from Human Studies

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1822
Author(s):  
Christian von Loeffelholz ◽  
Sina M. Coldewey ◽  
Andreas L. Birkenfeld
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Mammalian Cells ◽  
De Novo ◽  
Adenosine Monophosphate ◽  
De Novo Lipogenesis ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

5′AMP-activated protein kinase (AMPK) is known as metabolic sensor in mammalian cells that becomes activated by an increasing adenosine monophosphate (AMP)/adenosine triphosphate (ATP) ratio. The heterotrimeric AMPK protein comprises three subunits, each of which has multiple phosphorylation sites, playing an important role in the regulation of essential molecular pathways. By phosphorylation of downstream proteins and modulation of gene transcription AMPK functions as a master switch of energy homeostasis in tissues with high metabolic turnover, such as the liver, skeletal muscle, and adipose tissue. Regulation of AMPK under conditions of chronic caloric oversupply emerged as substantial research target to get deeper insight into the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Evidence supporting the role of AMPK in NAFLD is mainly derived from preclinical cell culture and animal studies. Dysbalanced de novo lipogenesis has been identified as one of the key processes in NAFLD pathogenesis. Thus, the scope of this review is to provide an integrative overview of evidence, in particular from clinical studies and human samples, on the role of AMPK in the regulation of primarily de novo lipogenesis in human NAFLD.

scholarly journals Non-alcoholic fatty liver disease: the hepatic consequence of obesity and the metabolic syndrome

2010 ◽  
Vol 69 (2) ◽  
pp. 211-220 ◽  
Author(s):  
J. Bernadette Moore
Keyword(s):  
Metabolic Syndrome ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Response To Treatment ◽  
Health Concern ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is now the most common liver disease in both adults and children worldwide. As a disease spectrum, NAFLD may progress from simple steatosis to steatohepatitis, advanced fibrosis and cirrhosis. An estimated 20–35% of the general population has steatosis, 10% of whom will develop the more progressive non-alcoholic steatohepatitis associated with markedly increased risk of cardiovascular- and liver-related mortality. Development of NAFLD is strongly linked to components of the metabolic syndrome including obesity, insulin resistance, dyslipidaemia and type 2 diabetes. The recognition that NAFLD is an independent risk factor for CVD is a major public health concern. There is a great need for a sensitive non-invasive test for the early detection and assessment of the stage of NAFLD that could also be used to monitor response to treatment. The cellular and molecular aetiology of NAFLD is multi-factorial; genetic polymorphisms influencing NAFLD have been identified and nutrition is a modifiable environmental factor influencing NAFLD progression. Weight loss through diet and exercise is the primary recommendation in the clinical management of NAFLD. The application of systems biology to the identification of NAFLD biomarkers and factors involved in NAFLD progression is an area of promising research.

scholarly journals Helicobacter pylori and Metabolic Diseases

2020 ◽  
Vol 20 (1) ◽  
pp. 21-28 ◽  
Author(s):  
Sung Eun Kim
Keyword(s):  
Helicobacter Pylori ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Gastrointestinal Disorders ◽  
Systemic Effects ◽  
Peptic Ulcers ◽  
Alcoholic Fatty Liver ◽  
H Pylori ◽  
The Relationship ◽  
Alcoholic Fatty Liver Disease

<i>Helicobacter pylori</i> (<i>H. pylori</i>) is one of the most common pathogens that can cause certain gastrointestinal disorders, such as gastritis, peptic ulcers, and gastric cancer. Recently, interest in the systemic effects of <i>H. pylori</i> on extragastric manifestations is increasing. Representative diseases include hematologic, cardiovascular, neurodegenerative, autoimmune, dermatologic, allergic, hepatobiliary, and metabolic diseases. Among them, since the prevalence of metabolic diseases is on the rise worldwide, the relationship between <i>H. pylori</i> infection and metabolic diseases has become an interesting research issue. Many studies have been conducted to clarify any association. However, the results of those studies still remain controversial. This review focuses on recently published studies to investigate the relationship between <i>H. pylori</i> infection and metabolic diseases, including diabetes mellitus, metabolic syndrome, obesity, and non-alcoholic fatty liver disease, and their associated pathophysiology.

Endoscopic Duodenal Mucosal Resurfacing for the Treatment of Type 2 Diabetes

2018 ◽  
Vol 36 (4) ◽  
pp. 322-324 ◽  
Author(s):  
Alia Hadefi ◽  
Vincent Huberty ◽  
Arnaud Lemmers ◽  
Marianna Arvanitakis ◽  
David Maggs ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bypass Surgery ◽  
Metabolic Diseases ◽  
Invasive Procedure ◽  
Diabetic Patients ◽  
Intestinal Bypass ◽  
Alcoholic Fatty Liver ◽  
Glucose Homoeostasis ◽  
Alcoholic Fatty Liver Disease

Type 2 diabetes is a pandemic disease with an incidence that has risen steadily over recent decades. Experimental evidence in animals has demonstrated that intestinal bypass surgery of the upper small intestine, particularly the duodenum, has an important role in glucose homoeostasis. Furthermore, Roux-en-Y bypass performed as bariatric surgery has shown to correct hyperglycaemia from the first postoperative days in obese diabetic patients. Therefore, on the basis of these considerations, duodenal mucosal resurfacing was studied in type 2 diabetes patients as a minimally invasive procedure that could offer an alternative treatment for these patients. Further studies, and particularly large controlled trials, are needed to determine the place of this procedure in the treatment of type 2 diabetes as well as other metabolic diseases such as non-alcoholic fatty liver disease/non-alcoholic steatohepatitis.

Blood triacylglycerols: a lipidomic window on diet and disease

2016 ◽  
Vol 44 (2) ◽  
pp. 638-644 ◽  
Author(s):  
Francis Sanders ◽  
Ben McNally ◽  
Julian L. Griffin
Keyword(s):  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Clinical Chemistry ◽  
Total Concentration ◽  
Direct Infusion ◽  
Alcoholic Fatty Liver ◽  
Tissue Extracts ◽  
The Individual ◽  
Alcoholic Fatty Liver Disease

Although the measurement of triacylglycerols (TAGs) by clinical chemistry has been used in the diagnosis of a range of metabolic diseases, such approaches ignore the different species of TAGs that contribute to the total concentration. With the advent of LC and direct infusion forms of MS it is now possible to profile the individual TAGs in blood plasma or tissue extracts. This mini review surveys the information that is obtainable from the lipidomic profiling of TAGs in following metabolic diseases such as type 2 diabetes (T2DM), cardiovascular disease (CVD) and non-alcoholic fatty liver disease, as well as the development of insulin resistance and obesity.

Bile acids and the metabolic syndrome

2019 ◽  
Vol 56 (3) ◽  
pp. 326-337 ◽  
Author(s):  
Emma Rose McGlone ◽  
Stephen R Bloom
Keyword(s):  
Diabetes Mellitus ◽  
Bile Acid ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Metabolic Effects ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Alcoholic Fatty Liver Disease

Bile acids have important roles in the regulation of lipid, glucose and energy metabolism. Metabolic diseases linked to obesity, including type 2 diabetes mellitus and non-alcoholic fatty liver disease, are associated with dysregulation of bile acid homeostasis. Here, the basic chemistry and regulation of bile acids as well as their metabolic effects will be reviewed. Changes in circulating bile acids associated with obesity and related diseases will be reviewed. Finally, pharmaceutical manipulation of bile acid homeostasis as therapy for metabolic diseases will be outlined.

scholarly journals Curcumin in Metabolic Health and Disease

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4440
Author(s):  
Marzena Jabczyk ◽  
Justyna Nowak ◽  
Bartosz Hudzik ◽  
Barbara Zubelewicz-Szkodzińska
Keyword(s):  
Cardiovascular Disease ◽  
Fatty Liver Disease ◽  
Metabolic Disorders ◽  
Metabolic Diseases ◽  
Polycystic Ovary ◽  
Epidemiological Studies ◽  
Ovary Syndrome ◽  
Alcoholic Fatty Liver ◽  
Health And Disease ◽  
Alcoholic Fatty Liver Disease

In recent years, epidemiological studies have suggested that metabolic disorders are nutritionally dependent. A healthy diet that is rich in polyphenols may be beneficial in the treatment of metabolic diseases such as polycystic ovary syndrome, metabolic syndrome, non-alcoholic fatty liver disease, cardiovascular disease, and, in particular, atherosclerosis. Curcumin is a polyphenol found in turmeric and has been reported to have antioxidant, anti-inflammatory, hepatoprotective, anti-atherosclerotic, and antidiabetic properties, among others. This review summarizes the influence of supplementation with curcumin on metabolic parameters in selected metabolic disorders.

scholarly journals New Mammalian Glycerol-3-Phosphate Phosphatase: Role in β-Cell, Liver and Adipocyte Metabolism

2021 ◽  
Vol 12 ◽  
Author(s):  
Elite Possik ◽  
Anfal Al-Mass ◽  
Marie-Line Peyot ◽  
Rasheed Ahmad ◽  
Fahd Al-Mulla ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Specific Reference ◽  
Alcoholic Fatty Liver ◽  
Cardiometabolic Diseases ◽  
Glucose Levels ◽  
Phosphoglycolate Phosphatase ◽  
Elevated Glucose ◽  
Glucose Stimulated Insulin Secretion ◽  
Alcoholic Fatty Liver Disease

Cardiometabolic diseases, including type 2 diabetes, obesity and non-alcoholic fatty liver disease, have enormous impact on modern societies worldwide. Excess nutritional burden and nutri-stress together with sedentary lifestyles lead to these diseases. Deranged glucose, fat, and energy metabolism is at the center of nutri-stress, and glycolysis-derived glycerol-3-phosphate (Gro3P) is at the crossroads of these metabolic pathways. Cellular levels of Gro3P can be controlled by its synthesis, utilization or hydrolysis. The belief that mammalian cells do not possess an enzyme that hydrolyzes Gro3P, as in lower organisms and plants, is challenged by our recent work showing the presence of a Gro3P phosphatase (G3PP) in mammalian cells. A previously described phosphoglycolate phosphatase (PGP) in mammalian cells, with no established physiological function, has been shown to actually function as G3PP, under physiological conditions, particularly at elevated glucose levels. In the present review, we summarize evidence that supports the view that G3PP plays an important role in the regulation of gluconeogenesis and fat storage in hepatocytes, glucose stimulated insulin secretion and nutri-stress in β-cells, and lipogenesis in adipocytes. We provide a balanced perspective on the pathophysiological significance of G3PP in mammals with specific reference to cardiometabolic diseases.

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