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Ceramide inflammation

Mateusz Maciejczyk, Ewa Żebrowska, Adrian Chabowski
The latest studies have indicated a strong relationship between systemic insulin resistance (IR) and higher incidence of neurodegeneration, dementia, and mild cognitive impairment. Although some of these abnormalities could be explained by chronic hyperglycaemia, hyperinsulinemia, dyslipidaemia, and/or prolonged whole-body inflammation, the key role is attributed to the neuronal redox imbalance and oxidative damage. In this mini review, we provide a schematic overview of intracellular oxidative stress and mitochondrial abnormalities in the IR brain...
February 18, 2019: International Journal of Molecular Sciences
Christine Feillet-Coudray, Gilles Fouret, Claire Vigor, Béatrice Bonafos, Bernard Jover, Agnieszka Blachnio-Zabielska, Jennifer Rieusset, François Casas, Sylvie Gaillet, Jean Francois Landrier, Thierry Durand, Charles Coudray
Inflammation and oxidative stress are thought to be involved in, or associated with, the development of obesity, dyslipidemia, hepatic steatosis, and insulin resistance. This work was designed to determine the evolution of inflammation and oxidative stress during onset and progression of hepatic steatosis and glucose intolerance. Seventy-five male Wistar rats were divided to control and high-fat high-fructose (HFHFr) groups. A subgroup of each group was sacrificed at 4, 8, 12, 16, and 20 weeks. HFHFr-fed rats exhibited overweight, glucose intolerance, and hepatic steatosis with increased contents of hepatic diacylglycerols and ceramides...
February 14, 2019: Lipids
Wei Zhao, Xueyin Wang, Amy A Deik, David B Hanna, Tao Wang, Sabina A Haberlen, Sanjiv J Shah, Jason M Lazar, Howard N Hodis, Alan L Landay, Bing Yu, Deborah Gustafson, Kathryn Anastos, Wendy S Post, Clary B Clish, Robert C Kaplan, Qibin Qi
BACKGROUND: Ceramides have been implicated in the pathophysiology of HIV infection and cardiovascular disease (CVD). However, no study, to our knowledge, has evaluated circulating ceramide levels in association with subclinical CVD risk among HIV-infected individuals. METHODS: Plasma levels of four ceramide species (C16:0, C22:0, C24:0 and C24:1) were measured among 398 women (73% HIV+) and 339 men (68% HIV+) without carotid artery plaques at baseline from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study...
February 14, 2019: Circulation
Zhixing He, Lijun Du, Yuehai Ke, Chengping Wen, Yun Zhang
Protein phosphatase 2A (PP2A) is one main serine/threonine phosphatase in eukaryotes, and its activation changes have been linked to modulation of numerous pathological processes, such as cancer, inflammation, fibrosis, and neurodegenerative diseases. Acute respiratory distress syndrome (ARDS), the major cause of respiratory failure, remains with limited therapies available up to now. Alveolar macrophages (AMs) are essential to innate immunity and host defense, participating in the pathogenesis of ARDS. As a result, AMs are considered as a potential therapeutic target for ARDS...
January 25, 2019: Inflammation
Vahid Reza Askari, Reza Shafiee-Nick
AIMS: Neuroinflammation is observed as a routine characterization of neurodegenerative disorders such as dementia, multiple sclerosis (MS) and Alzheimer's diseases (AD). Scientific evidence propounds both of the neuromodulatory and immunomodulatory effects of CB2 in the immune system. β-Caryophyllene (BCP) is a dietary selective CB2 agonist, which deserves the anti-inflammatory and antioxidant effects at both low and high doses through activation of the CB2 receptor. METHODS: In this study, we investigated the protective effects of a broad range concentration of BCP against LPS-induced primary microglia cells inflammation and M1 /M2 imbalance and identifying the portion of the involvement of related signaling pathways on BCP effects using pharmacological antagonists of CB2 , PPAR-γ, and sphingomyelinase (SMase)...
January 5, 2019: Life Sciences
Stacey N Keenan, Ruth C Meex, Jennifer C Y Lo, Andrew Ryan, Shuai Nie, Magdalene K Montgomery, Matthew J Watt
Defects in hepatic lipid metabolism cause non-alcoholic fatty liver disease and insulin resistance, and these pathologies are closely linked. Regulation of lipid droplet metabolism is central to the control of intracellular fatty acid fluxes and perilipin (PLIN) 5 is important in this process. We examined the role of PLIN5 on hepatic lipid metabolism and systemic glycemic control using liver-specific Plin5 deficient mice ( Plin5 LKO ). Hepatocytes isolated from Plin5 LKO mice exhibited marked changes in lipid metabolism characterized by decreased fatty acid uptake and storage, decreased fatty acid oxidation that was associated with reduced contact between lipid droplets and mitochondria, and reduced triglyceride secretion...
January 7, 2019: Diabetes
Jelske N van der Veen, Susanne Lingrell, Nicholas McCloskey, Nicholas D LeBlond, Danny Galleguillos, Yuan Y Zhao, Jonathan M Curtis, Simonetta Sipione, Morgan D Fullerton, Dennis E Vance, René L Jacobs
Phosphatidylethanolamine N-methyltransferase (PEMT) is an important enzyme in hepatic phosphatidylcholine (PC) biosynthesis. Pemt-/- mice fed a high-fat diet are protected from obesity and whole-body insulin resistance. However, Pemt-/- mice develop severe nonalcoholic steatohepatitis (NASH). Because NASH is often associated with hepatic insulin resistance, we investigated whether the increased insulin sensitivity in Pemt-/- mice was restricted to nonhepatic tissues or whether the liver was also insulin sensitive...
January 7, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Åke Nilsson, Rui-Dong Duan
The digestion of choline phospholipids is important for choline homeostasis, lipid signalling, postprandial lipid and energy metabolism, and interaction with intestinal bacteria. The digestion is mediated by the combined action of pancreatic and mucosal enzymes. In the proximal small intestine hydrolysis of phosphatidylcholine (PC) to 1-lyso-PC and FFA by the pancreatic phospholipase A2 IB coincides with the digestion of the dietary triacylglycerols by lipases, but part of the PC digestion is extended and must be mediated by other enzymes as the jejunoileal brush border phospholipase B/lipase and mucosal secreted phospholipase A2 X...
December 21, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Nana Watanabe, Takuya Suzuki, Yuya Yamazaki, Kozue Sugiyama, Seiji Koike, Megumi Nishimukai
Plasmalogen (Pls) is a glycerophospholipid derived from alkyl phospholipid (Alk) with antioxidant functions in vivo. The present study investigated the effects of ether phospholipids, such as Pls and Alk, on intercellular lipid barriers in the skin of NC/Nga mice, a model of atopic dermatitis (AD). NC/Nga mice fed Alk showed increased plasma levels of Alk and Pls. The AD-related changes in ceramide composition in the skin were abrogated by oral administration of Alk. Moreover, Alk suppressed skin inflammation in AD mice...
December 20, 2018: Bioscience, Biotechnology, and Biochemistry
Vikram Paranjpe, Jeremy Tan, Jason Nguyen, John Lee, Jeremy Allegood, Anat Galor, Nawajes Mandal
PURPOSE: Sphingolipids (SPL) play roles in cell signaling, inflammation, and apoptosis. Changes in SPL composition have been reported in individuals with MGD, but associations between clinical signs of MGD and compositional changes in meibum SPLs have not been examined. METHODS: Forty-three individuals underwent a tear film assessment. Groups were split into those with good or poor quality meibum. Meibum was collected then analyzed with liquid chromatography-mass spectroscopy to quantify SPL classes...
December 12, 2018: Ocular Surface
Mita Varghese, Cameron Griffin, Kaitlin McKernan, Leila Eter, Nicholas Lanzetta, Devyani Agarwal, Simin Abrishami, Kanakadurga Singer
Males are known to have profound adipose tissue macrophage (ATM) accumulation in gonadal white adipose tissue (GWAT) during obesity, whereas females are protected from such an inflammatory response even with increased adiposity. The inflammatory tone in males is linked to insulin resistance and might be the underlying cause for sex differences in metabolic disease. Factors regulating the meta-inflammatory response remain unclear but enhanced lipid storage in females may explain the reduced inflammatory response to high-fat diets...
February 1, 2019: Endocrinology
Chao Zhao, Lin Zhu, Ruijin Li, Hailin Wang, Zongwei Cai
Exposure to airborne particulate matter (PM) 2.5 induced various adverse health effects, such as metabolic syndrome, systemic inflammation and respiratory infection. However, a global influence of PM2.5 -induced metabolic and proteomic disorders remains confusing, and the underlying mechanism is still under-explored. Herein, LC-MS/MS-based metabolomics, lipidomics and isobaric tags for relative and absolute quantification (iTRAQ)-based proteomics were applied to analyze the toxicological characteristics of PM2...
December 1, 2018: Environmental Pollution
Kinga Czubowicz, Sylwia Wójtowicz, Przemysław Leonard Wencel, Robert Piotr Strosznajder
Alzheimer's disease (AD) is characterized by alterations of amyloid precursor protein (APP) metabolism, accumulation of amyloid  peptides (A), hyperphosphorylation of Tau proteins and also by sphingolipids disturbances. These changes lead to oxidative stress, mitochondria dysfunction, synaptic loss and neuro-inflammation. It is known that A may promote ceramides formation and reversely, ceramides could stimulate A peptides release. However, the effect of ceramide and sphingosine-1-phosphate (S1P) on APP metabolism has not been fully elucidated...
2018: Folia Neuropathologica
Teresa De Vita, Clara Albani, Natalia Realini, Marco Migliore, Abdul Basit, Giuliana Ottonello, Andrea Cavalli
Alzheimer's disease (AD) is a slow-progressing disease of the brain characterized by symptoms such as impairment of memory and other cognitive functions. AD is associated with an inflammatory process that involves astrocytes and microglial cells, among other components. Astrocytes are the most abundant type of glial cells in the central nervous system (CNS). They are involved in inducing neuroinflammation. The present study uses astrocyte-neuron co-cultures to investigate how ARN14494, a serine palmitoyltransferase (SPT) inhibitor, affects the CNS in terms of anti-inflammation and neuroprotection...
November 27, 2018: ACS Chemical Neuroscience
Fabian Ps Yu, Ben Sajdak, Jakub Sikora, Alexander E Salmon, Murtaza S Nagree, Jiří Gurka, Iris S Kassem, Daniel M Lipinski, Joseph Carroll, Jeffrey A Medin
Farber Disease (FD) is a debilitating lysosomal storage disorder characterized by severe inflammation and neurodegeneration. FD is caused by mutations in the ASAH1 gene resulting in deficient acid ceramidase (ACDase) activity. Patients with ACDase deficiency exhibit a broad clinical spectrum. In classical cases, patients develop hepatosplenomegaly, nervous system involvement, and childhood mortality. Ocular manifestations include decreased vision, a grayish appearance to the retina with a cherry red spot, and nystagmus...
November 22, 2018: American Journal of Pathology
Prashant Chauhan, Bhaskar Saha
Immunometabolic framework provides a way to understand the immune regulation via cell intrinsic metabolic fluxes and metabolites during infections, tumors, and inflammatory disorders. During these diseases, the immune cells are activated requiring more energy and moderating their metabolic functions. The two categories of metabolic alterations are therefore causally associated with energy derivation and cellular functions. Pathogens, tumors and inflammation target energy metabolism, primarily glucose uptake, glucose catabolism, gluconeogenesis for continuing lipid metabolism through mainstream pathways such as glycolysis, tricarboxylic acid cycle, mitochondrial respiration and pentose phosphate pathway...
November 21, 2018: Cytokine
Chao Yang, Qing Jiang
Nuclear factor-κB (NF-κB) regulates inflammation and cell survival, and is considered a potential target for anti-inflammatory and anti-cancer therapy. δ-Tocotrienol (δTE), a vitamin E form, has been shown to inhibit NF-κB, but the mechanism underlying this action is not clear. In the present study, we show that δTE inhibited TNF-α-induced activation of NF-κB and LPS-stimulated IL-6 in a dose- and time-dependent manner in Raw 264.7 macrophages. δTE potently inhibited TNF-α-induced phosphorylation of transforming growth factor β-activated kinase 1 (TAK1), an upstream kinase essential for the activation of NF-κB...
November 3, 2018: Journal of Nutritional Biochemistry
Janine Schulte-Zweckel, Tabea Schneidewind, Jose Luis Abad, Andreas Brockmeyer, Petra Janning, Gemma Triola
Ceramide plays key roles in autophagy, inflammation and apoptosis. However, little is known about the molecular mechanisms regulating its function and only a handful of cellular effectors are known for this lipid. Here we show that azide-tagged sphingolipids are powerful tools to identify ceramide targets. The combination of a protein array analysis and a mass spectrometry-based proteomic profiling successfully detects known ceramide-binding proteins and identifies others not yet reported, several of which we validated using a variety of techniques...
November 20, 2018: Chemical Communications: Chem Comm
Mariana Nikolova-Karakashian
Sphingolipids are class of metabolically distinct lipids that play structural and signaling functions in all organisms. Sphingolipid metabolism is deregulated during various diseases such as cancer, neurological and immune disorders, and metabolic syndrome. With the advancement of sphingo-lipidomics and sphingo-genomics, an understanding of the specific roles of ceramide, the quintessential bioactive sphingolipid, in fatty liver disease has taken shape. Two major pathways for ceramide generation, the de novo pathway and the sphingomyelinase pathway are activated in the course of both, the non-alcoholic and the alcoholic, forms of fatty liver disease...
December 2018: Advances in Biological Regulation
Svenja Plöhn, Bärbel Edelmann, Lukasz Japtok, Xingxuan He, Matthias Hose, Wiebke Hansen, Edward H Schuchman, Anja Eckstein, Utta Berchner-Pfannschmidt
Purpose: Graves' orbitopathy (GO) is an autoimmune orbital disorder associated with Graves' disease caused by thyrotropin receptor autoantibodies. Orbital fibroblasts (OFs) and CD40 play a key role in disease pathogenesis. The bioactive lipid sphingosine-1-phosphate (S1P) has been implicated in promoting adipogenesis, fibrosis, and inflammation in OFs. We investigated the role of CD40 signaling in inducing S1P activity in orbital inflammation. Methods: OFs and T cells were derived from GO patients and healthy control (Ctl) persons...
November 1, 2018: Investigative Ophthalmology & Visual Science
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