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Ceramide inflammation

Natalia Presa, Robin D Clugston, Susanne Lingrell, Samuel E Kelly, Alfred H Merrill, Sayantan Jana, Zamaneh Kassiri, Antonio Gómez-Muñoz, Dennis E Vance, Rene L Jacobs, Jelske N van der Veen
Phosphatidylethanolamine N-methyltransferase (PEMT) converts phosphatidylethanolamine (PE) to phosphatidylcholine (PC), mainly in the liver. Pemt-/- mice are protected from high-fat diet (HFD)-induced obesity and insulin resistance, but develop severe non-alcoholic fatty liver disease (NAFLD) when fed a HFD, mostly due to impaired VLDL secretion. Oxidative stress is thought to be an essential factor in the progression from simple steatosis to steatohepatitis. Vitamin E is an antioxidant that has been clinically used to improve NAFLD pathology...
October 6, 2018: Biochimica et biophysica acta. Molecular basis of disease
Marta Ordoñez, Natalia Presa, Asier Dominguez-Herrera, Miguel Trueba, Antonio Gomez-Muñoz
We showed previously that ceramide kinase (CerK) expression increases during adipogenesis pointing to a relevant role of intracellular C1P in this process. In the present work we demonstrate that administration of exogenous C1P inhibits the differentiation of 3T3-L1 pre-adipocytes into mature adipocytes through a mechanism involving activation of extracellularly regulated kinases (ERK) 1-2. Exogenous C1P reduced the accumulation of lipid droplets and the content of triacylglycerol in these cells, and potently inhibited the expression of the early and late adipogenic markers C/EBPβ and PPARγ, respectively...
September 27, 2018: Experimental Cell Research
Paul T Reidy, Alec I McKenzie, Ziad Mahmassani, Vincent R Morrow, Nikol Yonemura, Paul N Hopkins, Robin L Marcus, Matthew T Rondina, Yu Kuei Lin, Micah J Drummond
KEY POINT: Insulin sensitivity (as determined by a hyperinsulinemic-euglycemic clamp) decreased 15% after reduced activity but surprisingly rebounded above Pre by 14% after the recovery period despite not fully returning to baseline physical activity levels. Changes in insulin sensitivity in response to reduced activity were primarily driven by men but not women. There were modest changes in ceramides (nuclear/myofibrillar fraction and serum) following reduced activity and recovery but in the absence of major changes to body composition (ie, fat mass) ceramides were not related to changes in inactivity-induced insulin sensitivity in healthy older adults...
September 8, 2018: Journal of Physiology
Victor García-González, José Fernando Díaz-Villanueva, Octavio Galindo-Hernández, Israel Martínez-Navarro, Gustavo Hurtado-Ureta, Abril Alicia Pérez-Arias
Ceramides are key lipids in energetic-metabolic pathways and signaling cascades, modulating critical physiological functions in cells. While synthesis of ceramides is performed in endoplasmic reticulum (ER), which is altered under overnutrition conditions, proteins associated with ceramide metabolism are located on membrane arrangement of mitochondria and ER (MAMs). However, ceramide accumulation in meta-inflammation, condition that associates obesity with a chronic low-grade inflammatory state, favors the deregulation of pathways such as insulin signaling, and induces structural rearrangements on mitochondrial membrane, modifying its permeability and altering the flux of ions and other molecules...
August 26, 2018: International Journal of Molecular Sciences
Guangbi Li, Qinghua Zhang, Jinni Hong, Joseph K Ritter, Pin-Lan Li
The pannexin-1 (Panx1) channel has been reported to mediate the release of ATP that is involved in local tissue inflammation, obesity, and many chronic degenerative diseases. It remains unknown whether Panx1 is present in podocytes and whether this channel in podocytes mediates ATP release leading to glomerular inflammation or fibrosis. To answer these questions, we first characterized the expression of Panx channels in podocytes. Among the three known pannexins, Panx1 was the most enriched in podocytes, either cultured or native in mouse glomeruli...
October 2018: Biochimica et biophysica acta. Molecular and cell biology of lipids
Djahida Bedja, Wenwen Yan, Viren Lad, Domenica Iocco, Nickash Sivakumar, Veera Venkata Ratnam Bandaru, Subroto Chatterjee
Sphingolipids have been accorded numerous biological functions however, the effects of feeding a western diet (diet rich in cholesterol and fat) on skin phenotypes, and color is not known. Here, we observed that chronic high-fat and high-cholesterol diet intake in a mouse model of atherosclerosis (ApoE-/-) decreases the level of ceramides and glucosylceramide. At the expense of increased levels of lactosylceramide due to an increase in the expression of lactosylceramide synthase (GalT-V). This is accompanied with neutrophil infiltration into dermis, and enrichment of tumor necrosis factor-stimulated gene-6 (TSG-6) protein...
July 30, 2018: Scientific Reports
Domenico Sergi, Amanda C Morris, Darcy E Kahn, Fiona H McLean, Elizabeth A Hay, Phil Kubitz, Alasdair MacKenzie, Maria G Martinoli, Janice E Drew, Lynda M Williams
A high-fat diet induces hypothalamic inflammation in rodents which, in turn, contributes to the development of obesity by eliciting both insulin and leptin resistance. However, the mechanism by which long-chain saturated fatty acids trigger inflammation is still contentious. To elucidate this mechanism, the effect of fatty acids on the expression of the pro-inflammatory cytokines IL-6 and TNFα was investigated in the mHypoE-N42 hypothalamic cell line (N42). N42 cells were treated with lauric acid (LA) and palmitic acid (PA)...
July 21, 2018: Nutritional Neuroscience
Elise Dargelos, Valentine Renaud, Marion Decossas, Corinne Bure, Olivier Lambert, Sylvie Poussard
Chronic diseases are characterized by the production of pro-inflammatory cytokines such than TNF-α and are frequently correlated with muscle wasting conditions. Among the pleiotropic effects of TNF-α within the cell, its binding to TNFR1 receptor has been shown to activate sphingomyelinases leading to the production of ceramides. Sphingomyelinases and TNF receptor have been localized within caveolae which are specialized RAFT enriched in cholesterol and sphingolipids. Because of their inverted omega shape, maintained by the oligomerization of specialized proteins, caveolins and cavins, caveolae serve as membrane reservoir therefore providing mechanical protection to plasma membranes...
September 15, 2018: Experimental Cell Research
Dharmendra K Yadav, Surendra Kumar, Eun-Ha Choi, Praveen Sharma, Sanjeev Misra, Mi-Hyun Kim
In recent years, the role of reactive oxygen species (ROS) in regulating cancer cell apoptosis, inflammation, cell ischemia, and cell signaling pathways has been well established. The most common sources of intracellular ROS are the mitochondrial electron transport system, NADH oxidase, and cytochrome P450. In this study, we investigated the dynamics and permeability of ROS using molecular dynamics (MD) simulations on native skin-lipid bilayer membranes. Native skin-lipid bilayers are composed of ceramide, cholesterol, and free fatty acid in an almost equal molar ratio (1:1:1)...
2018: Frontiers in Pharmacology
Yanchun Li, Zhongyang Lu, Ji Hyun Ru, Maria F Lopes-Virella, Timothy J Lyons, Yan Huang
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and consumption of high-fat diet (HFD) is a risk factor for NAFLD. The HFD not only increases intake of saturated fatty acid (SFA), but also induces metabolic endotoxemia, a HFD-associated increase in circulating lipopolysaccharide (LPS). Although it is known that SFA or LPS promotes hepatic inflammation, a hallmark of NAFLD, it remains unclear how SFA in combination with LPS stimulates host inflammatory response in hepatocytes...
July 10, 2018: American Journal of Physiology. Endocrinology and Metabolism
Kenneth P Hough, Landon S Wilson, Jennifer L Trevor, John G Strenkowski, Njeri Maina, Young-Il Kim, Marion L Spell, Yong Wang, Diptiman Chanda, Jose Rodriguez Dager, Nirmal S Sharma, Miranda Curtiss, Veena B Antony, Mark T Dransfield, David D Chaplin, Chad Steele, Stephen Barnes, Steven R Duncan, Jeevan K Prasain, Victor J Thannickal, Jessy S Deshane
Asthma is a chronic inflammatory disease process involving the conductive airways of the human lung. The dysregulated inflammatory response in this disease process may involve multiple cell-cell interactions mediated by signaling molecules, including lipid mediators. Extracellular vesicles (EVs) are lipid membrane particles that are now recognized as critical mediators of cell-cell communication. Here, we compared the lipid composition and presence of specific lipid mediators in airway EVs purified from the bronchoalveolar lavage (BAL) fluid of healthy controls and asthmatic subjects with and without second-hand smoke (SHS) exposure...
July 9, 2018: Scientific Reports
Han Fang, Robert L Judd
Adipose tissue is now recognized as an important endocrine organ, capable of secreting a large number of endocrine factors which regulate a wide variety of physiological functions. Adiponectin is one such factor, secreted in large quantities primarily from adipose tissue. Adiponectin is posttranslationally modified from a 30-kDa monomeric protein into different multimers (low molecular weight or trimer, middle molecular weight or hexamer, and high molecular weight) and secreted into the circulation. Upon binding to its receptors, AdipoR1 and R2, adiponectin initiates a series of tissue-dependent signal transduction events, including phosphorylation of adenosine monophosphate (AMPK) and p38 mitogen-activated protein kinase (p38 MAPK), and increased peroxisome proliferator-activated receptor alpha (PPARα) ligand activity...
June 18, 2018: Comprehensive Physiology
Yongeun Kim, Anthony D Gromovsky, J Mark Brown, Soonkyu Chung
The activation of NLRP3 inflammasome in innate immune cells is associated with enhanced production of pro-inflammatory lipid mediator eicosanoids that play a crucial role in propagating inflammation. Gamma-tocotrienol (γT3) is an unsaturated vitamin E that has been demonstrated to attenuate NLRP3-inflammasome. However, the role of γT3 in regulating eicosanoid formation is unknown. We hypothesized that γT3 abolishes the eicosanoid production by modulating the macrophage lipidome. LPS-primed bone marrow-derived macrophages (BMDM) were stimulated with saturated fatty acids (SFA) along with γT3, and the effects of γT3 in modulating macrophage lipidome were quantified by using mass spectrometry based-shotgun lipidomic approaches...
August 2018: Journal of Nutritional Biochemistry
Geoffrey C Farrell, Fahrettin Haczeyni, Shivakumar Chitturi
Overnutrition, usually with obesity and genetic predisposition, lead to insulin resistance, which is an invariable accompaniment of nonalcoholic fatty liver disease (NAFLD). The associated metabolic abnormalities, pre- or established diabetes, hypertension and atherogenic dyslipidemia (clustered as metabolic syndrome) tend to be worse for nonalcoholic steatohepatitis (NASH), revealing it as part of a continuum of metabolic pathogenesis. The origins of hepatocellular injury and lobular inflammation which distinguish NASH from simple steatosis have intrigued investigators, but it is now widely accepted that NASH results from liver lipotoxicity...
2018: Advances in Experimental Medicine and Biology
Kazuhisa Iwabuchi
Although individuals are constantly exposed to infectious agents, these agents are generally resisted by the innate and acquired immune systems. Both the innate and acquired immune systems protect against invading organisms, but they differ functionally in several ways. The innate immune system is the body's inborn defense mechanism and the first line of defense against invading organisms, such as bacteria, fungi, and viruses. Glycosphingolipids (GSLs), which are expressed on the outer leaflet of plasma membranes (Murate et al...
2018: Methods in Molecular Biology
Ulrike G Glaser, Joachim Fandrey
Hypoxia due to rapid tumor growth with impaired neovascularization and inflammation resulting from immune cell activation are hallmarks of cancer. Hypoxia-inducible factors control transcriptional adaptation in response to low oxygen conditions, both in tumor and immune cells. In addition, sphingolipids become increasingly recognized as important cell mediators in tumor and inflammatory hypoxia. Recent studies have identified acid sphingomyelinase (ASM), a central enzyme in the sphingolipid metabolism, as a regulator of several types of stress stimuli pathways and an important player in the tumor microenvironment...
September 25, 2018: Biological Chemistry
Nadine Beckmann, Stephanie Kadow, Fabian Schumacher, Joachim R Göthert, Stefanie Kesper, Annette Draeger, Walter J Schulz-Schaeffer, Jiang Wang, Jan U Becker, Melanie Kramer, Claudine Kühn, Burkhard Kleuser, Katrin Anne Becker, Erich Gulbins, Alexander Carpinteiro
Farber disease (FD) is a rare lysosomal storage disorder resulting from acid ceramidase deficiency and subsequent ceramide accumulation. No treatments are clinically available and affected patients have a severely shortened lifespan. Due to the low incidence, the pathogenesis of FD is still poorly understood. Here, we report a novel acid ceramidase mutant mouse model that enables the study of pathogenic mechanisms of FD and ceramide accumulation. Asah1tmEx1 mice were generated by deletion of the acid ceramidase signal peptide sequence...
September 25, 2018: Biological Chemistry
Jeffrey W Meeusen, Leslie J Donato, Sandra C Bryant, Linnea M Baudhuin, Peter B Berger, Allan S Jaffe
OBJECTIVE: Ceramides are sphingolipids involved with cellular signaling. Synthesis of ceramides occurs in all tissues. Ceramides accumulate within tissues and the blood plasma during metabolic dysfunction, dyslipidemia, and inflammation. Elevations of ceramides are predictive of cardiovascular mortality. We sought to verify the utility of plasma concentrations of 4 ceramides: N-palmitoyl-sphingosine [Cer(16:0)], N-stearoyl-sphingosine [Cer(18:0)], N-nervonoyl-sphingosine [Cer(24:1)], and N-lignoceroyl-sphingosine [Cer(24:0)] in predicting major adverse cardiovascular events in a diverse patient population referred for coronary angiography...
June 14, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Junfei Jin, Zhongyang Lu, Yanchun Li, Ji Hyun Ru, Maria F Lopes-Virella, Yan Huang
It has been well established that patients with diabetes or metabolic syndrome (MetS) have increased prevalence and severity of periodontitis, an oral infection initiated by bacteria and characterized by tissue inflammation and destruction. To understand the underlying mechanisms, we have shown that saturated fatty acid (SFA), which is increased in patients with type 2 diabetes or MetS, and LPS, an important pathogenic factor for periodontitis, synergistically stimulate expression of proinflammatory cytokines in macrophages by increasing ceramide production...
October 2018: Journal of Leukocyte Biology
Ehrhardt Proksch
The pH plays an important physiological role in nature and humans. pH varies from 1 to 8 in human organs with tight regulation in blood and epithelia of barrier organs. The physiological pH of the stratum corneum is 4.1-5.8 and several mechanisms contribute to its formation: filaggrin degradation, fatty acid content, sodium-hydrogen exchanger (NHE1) activation and melanosome release. First, the acidic pH of the stratum corneum was considered to present an antimicrobial barrier preventing colonization (e.g. by Staphylococcus aureus and Malassezia)...
September 2018: Journal of Dermatology
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