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https://www.readbyqxmd.com/read/27922112/plasma-cathepsin-d-correlates-with-histological-classifications-of-fatty-liver-disease-in-adults-and-responds-to-intervention
#1
Sofie M A Walenbergh, Tom Houben, Sander S Rensen, Veerle Bieghs, Tim Hendrikx, Patrick J van Gorp, Yvonne Oligschlaeger, Mike L J Jeurissen, Marion J J Gijbels, Wim A Buurman, Anita C E Vreugdenhil, Jan Willem M Greve, Jogchum Plat, Marten H Hofker, Satish Kalhan, Jussi Pihlajamäki, Patrick Lindsey, Ger H Koek, Ronit Shiri-Sverdlov
Non-alcoholic steatohepatitis (NASH) is characterized by liver lipid accumulation and inflammation. The mechanisms that trigger hepatic inflammation are poorly understood and subsequently, no specific non-invasive markers exist. We previously demonstrated a reduction in the plasma lysosomal enzyme, cathepsin D (CatD), in children with NASH compared to children without NASH. Recent studies have raised the concept that non-alcoholic fatty liver disease (NAFLD) in adults is distinct from children due to a different histological pattern in the liver...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27920727/genetic-targeting-of-arginase-ii-in-mouse-prevents-renal-oxidative-stress-and-inflammation-in-diet-induced-obesity
#2
Ji Huang, Angana Rajapakse, Yuyan Xiong, Jean-Pierre Montani, François Verrey, Xiu-Fen Ming, Zhihong Yang
Obesity is associated with development and progression of chronic kidney disease (CKD). Recent evidence demonstrates that enhanced levels of the L-arginine:ureahydrolase, including the two isoenzymes arginase-I (Arg-I) and arginase-II (Arg-II) in vascular endothelial cells promote uncoupling of endothelial nitric oxide synthase (eNOS), leading to increased superoxide radical anion and decreased NO production thereby endothelial dysfunction. Arg-II but not Arg-I is abundantly expressed in kidney and the role of Arg-II in CKD is uncertain and controversial...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27919712/extracts-from-two-ubiquitous-mediterranean-plants-ameliorate-cellular-and-animal-models-of-neurodegenerative-proteinopathies
#3
Michelle Briffa, Stephanie Ghio, Johanna Neuner, Alison J Gauci, Rebecca Cacciottolo, Christelle Marchal, Mario Caruana, Christophe Cullin, Neville Vassallo, Ruben J Cauchi
A signature feature of age-related neurodegenerative proteinopathies is the misfolding and aggregation of proteins, typically amyloid-β (Aβ) in Alzheimer's disease (AD) and α-synuclein (α-syn) in Parkinson's disease (PD), into soluble oligomeric structures that are highly neurotoxic. Cellular and animal models that faithfully replicate the hallmark features of these disorders are being increasing exploited to identify disease-modifying compounds. Natural compounds have been identified as a useful source of bioactive molecules with promising neuroprotective capabilities...
December 2, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27919355/model-observational-bridging-study-on-the-effectiveness-of-ezetimibe-on-cardiovascular-morbidity-and-mortality-in-france-a-population-based-study
#4
Jean Ferrières, Jean Dallongeville, Michel Rossignol, Jacques Bénichou, J Jaime Caro, Denis Getsios, Luis Hernandez, Lucien Abenhaim, Lamiae Grimaldi-Bensouda
BACKGROUND: To evaluate the real-life impact of ezetimibe on cardiovascular (CV) morbidity and mortality in France. OBJECTIVE: To estimate the number of non-fatal and fatal CV events that could be prevented and corresponding number of patients needed to treat (NNT) with ezetimibe to prevent one CV event over 5 years. METHODS: Non-interventional 48-month follow-up cohort conducted in hypercholesterolemic patients starting on ezetimibe <3 months at study entry, either as monotherapy or combined with statins...
November 2016: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/27919227/high-light-stress-triggers-distinct-proteomic-responses-in-the-marine-diatom-thalassiosira-pseudonana
#5
Hong-Po Dong, Yue-Lei Dong, Lei Cui, Srinivasan Balamurugan, Jian Gao, Song-Hui Lu, Tao Jiang
BACKGROUND: Diatoms are able to acclimate to frequent and large light fluctuations in the surface ocean waters. However, the molecular mechanisms underlying these acclimation responses of diaotms remain elusive. RESULTS: In this study, we investigated the mechanism of high light protection in marine diatom Thalassiosira pseudonana using comparative proteomics in combination with biochemical analyses. Cells treated under high light (800 μmol photons m(-2)s(-1)) for 10 h were subjected to proteomic analysis...
December 5, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27918728/cholesterol-metabolism-in-rabbit-blastocysts-under-maternal-diabetes
#6
S Mareike Pendzialek, Maria Schindler, Torsten Plösch, Jacqueline Gürke, Elisa Haucke, Stefanie Hecht, Bernd Fischer, Anne Navarrete Santos
In the rabbit reproductive model, maternal experimentally induced insulin-dependent diabetes mellitus (expIDD) leads to accumulation of lipid droplets in blastocysts. Cholesterol metabolism is a likely candidate to explain such metabolic changes. Therefore, in the present study we analysed maternal and embryonic cholesterol concentrations and expression of related genes in vivo (diabetic model) and in vitro (embryo culture in hyperglycaemic medium). In pregnant expIDD rabbits, the serum composition of lipoprotein subfractions was changed, with a decrease in high-density lipoprotein cholesterol and an increase in very low-density lipoprotein cholesterol; in uterine fluid, total cholesterol concentrations were elevated...
December 6, 2016: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/27917915/blood-hsa-mir-122-5p-and-hsa-mir-885-5p-levels-associate-with-fatty-liver-and-related-lipoprotein-metabolism-the-young-finns-study
#7
Emma Raitoharju, Ilkka Seppälä, Leo-Pekka Lyytikäinen, Jorma Viikari, Mika Ala-Korpela, Pasi Soininen, Antti J Kangas, Melanie Waldenberger, Norman Klopp, Thomas Illig, Jaana Leiviskä, Britt-Marie Loo, Niku Oksala, Mika Kähönen, Nina Hutri-Kähönen, Reijo Laaksonen, Olli Raitakari, Terho Lehtimäki
MicroRNAs are involved in disease development and may be utilized as biomarkers. We investigated the association of blood miRNA levels and a) fatty liver (FL), b) lipoprotein and lipid pathways involved in liver lipid accumulation and c) levels of predicted mRNA targets in general population based cohort. Blood microRNA profiling (TaqMan OpenArray), genome-wide gene expression arrays and nuclear magnetic resonance metabolomics were performed for Young Finns Study participants aged 34-49 years (n = 871)...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27917887/13-methylberberine-a-berberine-analogue-with-stronger-anti-adipogenic-effects-on-mouse-3t3-l1-cells
#8
Yit-Lai Chow, Mami Sogame, Fumihiko Sato
Lipid metabolism modulation is a main focus of metabolic syndrome research, an area in which many natural and synthetic chemicals are constantly being screened for in vitro and in vivo activity. Berberine, a benzylisoquinoline plant alkaloid, has been extensively investigated for its anti-obesity effects and as a potential cholesterol and triglyceride-lowering drug. We screened 11 protoberberine and 2 benzophenanthridine alkaloids for their anti-adipogenic effects on 3T3-L1 adipocytes and found that 13-methylberberine exhibited the most potent activity...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27917506/comparative-in-vitro-toxicity-assessment-of-perfluorinated-carboxylic-acids
#9
Cecon T Mahapatra, Nur P Damayanti, Samuel C Guffey, Jennifer S Serafin, Joseph Irudayaraj, Maria S Sepúlveda
Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are synthetic fluorinated compounds that are highly bioaccumulative and persistent organic pollutants. Perfluorooctanoic acid (PFOA), an eight-carbon chain perfluorinated carboxylic acid, was used heavily for the production of fluoropolymers, but concerns have led to its replacement by shorter carbon chain homologues such as perfluorohexanoic acid (PFHxA) and perfluorobutanoic acid (PFBA). However, limited toxicity data exist for these substitutes. We evaluated the toxicity of PFOA, PFHxA and PFBA on a zebrafish liver cell line and investigated the effects of exposure on cell metabolism...
December 5, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27917474/germacrone-inhibits-adipogenesis-and-stimulates-lipolysis-via-the-amp-activated-protein-kinase-signalling-pathway-in-3t3-l1-preadipocytes
#10
Yuan-Ri Guo, Se-Young Choung
OBJECTIVES: In a previous study, we reported that Aster spathulifolius Maxim extract (ASE) inhibited lipid accumulation and adipocyte differentiation in 3T3-L1 cells. Of the components in ASE, germacrone (GM) was identified as a potent bioactive constituent. GM is known for its anticancer and antiviral activity. However, the effects of GM and the molecular mechanism by which GM regulates adipogenesis and lipolysis were not reported. Therefore, we investigated the effect of GM on adipogenesis and lipolysis and to elucidate its underlying molecular mechanism...
December 5, 2016: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/27916986/pharmacological-modulation-of-lmna-srsf1-dependent-splicing-abrogates-diet-induced-obesity-in-mice
#11
J Santo, C Lopez-Herrera, C Apolit, Y Bareche, L Lapasset, C Chavey, S Capozi, F Mahuteau, R Najman, P Fornarelli, I C Lopez-Mejía, G Béranger, F Casas, E-Z Amri, B Pau, D Scherrer, J Tazi
BAKGROUND/OBJECTIVES: Intense drug discovery efforts in the metabolic field highlight the need for novel strategies for the treatment of obesity. Alternative splicing (AS) and/or polyadenylation enable the LMNA gene to express distinct protein isoforms that exert opposing effects on energy metabolism and lifespan. Here we aimed to use the splicing factor SRSF1 that contribute to the production of these different isoforms as a target to uncover new anti-obesity drug. SUBJECTS/METHODS: Small molecules modulating SR protein activity and splicing, were tested for their abilities to interact with SRSF1 and to modulate LMNA (AS)...
December 5, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/27915128/cholesterol-reducing-agents-inhibit-assembly-of-type-i-parainfluenza-viruses
#12
Shringkhala Bajimaya, Tsuyoshi Hayashi, Tünde Frankl, Peter Bryk, Brian Ward, Toru Takimoto
Many enveloped RNA viruses utilize lipid rafts for the assembly of progeny virions, but the role of cholesterol, a major component of rafts, on paramyxovirus budding and virion formation is controversial. In this study, we analyzed the effects of FDA-approved cholesterol-reducing agents, gemfibrozil and lovastatin, on raft formation and assembly of human parainfluenza virus type 1 (hPIV1) and Sendai virus (SeV). Treatment of the human airway epithelial A549 cells with the agents, especially when combined, significantly decreased production of infectious hPIV1 and SeV...
December 1, 2016: Virology
https://www.readbyqxmd.com/read/27915031/acid-ceramidase-deficiency-is-characterized-by-a-unique-plasma-cytokine-and-ceramide-profile-that-is-altered-by-therapy
#13
Shaalee Dworski, Ping Lu, Aneal Khan, Bruno Maranda, John J Mitchell, Rossella Parini, Maja Di Rocco, Boris Hugle, Makoto Yoshimitsu, Bo Magnusson, Balahan Makay, Nur Arslan, Norberto Guelbert, Karoline Ehlert, Andrea Jarisch, Janet Gardner-Medwin, Rawane Dagher, Maria Teresa Terreri, Charles Marques Lorenco, Lilianna Barillas-Arias, Pranoot Tanpaiboon, Alexander Solyom, James S Norris, Xingxuan He, Edward H Schuchman, Thierry Levade, Jeffrey A Medin
Acid Ceramidase Deficiency (Farber Disease, FD) is an ultra-rare Lysosomal Storage Disorder that is poorly understood and often misdiagnosed as Juvenile Idiopathic Arthritis (JIA). Hallmarks of FD are accumulation of ceramides, widespread macrophage infiltration, splenomegaly, and lymphocytosis. The cytokines involved in this abnormal hematopoietic state are unknown. There are dozens of ceramide species and derivatives, but the specific ones that accumulate in FD have not been investigated. We used a multiplex assay to analyze cytokines and mass spectrometry to analyze ceramides in plasma from patients and mice with FD, controls, Farber patients treated by hematopoietic stem cell transplantation (HSCT), JIA patients, and patients with Gaucher disease...
November 30, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27914980/cloning-and-characterization-of-adipogenin-and-its-overexpression-enhances-fat-accumulation-of-bovine-myosatellite-cells
#14
Yang Liu, Bijie Jiang, Changzhen Fu, Ruijie Hao
Adipogenin (ADIG) is an adipocyte-specific membrane protein highly expressed in adipose tissues and is increased during the adipocyte differentiation. However, the roles and mechanisms of ADIG on fat accumulation and adipocyte differentiation in ex vivo still largely unknown. In this study, we isolated bovine myosatellite cells based on adhesion characteristics to investigate whether ADIG overexpression could promote trans-differentiation and increase fat accumulation in myosatellite cells. Immunofluorescence labeling was then used for the phenotypic characteristics of myosatellite...
November 30, 2016: Gene
https://www.readbyqxmd.com/read/27914812/protective-effects-of-gomisin-n-against-hepatic-steatosis-through-ampk-activation
#15
Ye-Rang Yun, Ji-Hyun Kim, Ji Ha Kim, Myeong Ho Jung
Gomisin N (GN) is a phytochemical derived from Schisandra chinensis. It has been reported to exert a protective effect against hepatic steatosis by attenuating endoplasmic recticulum (ER) stress. However, the detailed mechanism by which GN inhibits hepatic steatosis remains to be elucidated. In this study, we examined whether GN activates AMP-activated protein kinase (AMPK) and exerts therapeutic effects on liver X receptor (LXR)- or palmitic acid (PA)-induced triglyceride (TG) accumulation in HepG2 cells. Furthermore, in vivo protective effects of GN against hepatic steatosis were assessed in high-fat diet (HFD)-induced obese mice...
November 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27914517/effect-of-flaxseed-oil-and-microalgae-dha-on-the-production-performance-fatty-acids-and-total-lipids-of-egg-yolk-and-plasma-in-laying-hens
#16
M Neijat, O Ojekudo, J D House
The incorporation of omega-3 polyunsaturated fatty acids (PUFA) in the egg is dependent on both the transfer efficiency of preformed dietary omega-3 fatty acids to the eggs as well as endogenous PUFA metabolism and deposition. Employing an experimental design consisting of 70 Lohmann LSL-Classic hens (n=10/treatment) in a 6-week feeding trial, we examined the impact of graded levels of either flaxseed oil (alpha-linolenic acid, ALA) or algal DHA (preformed docosahexaenoic acid, DHA), each supplying 0.20%, 0...
December 2016: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/27913612/mechanisms-in-endocrinology-skeletal-muscle-lipotoxicity-in-insulin-resistance-and-type-2-diabetes-a-causal-mechanism-or-an-innocent-bystander
#17
REVIEW
Charlotte Brøns, Louise Groth Grunnet
Dysfunctional adipose tissue is associated with an increased risk of developing type 2 diabetes (T2D). One characteristic of a dysfunctional adipose tissue is the reduced expandability of the subcutaneous adipose tissue leading to ectopic storage of fat in organs and/or tissues involved in the pathogenesis of T2D that can cause lipotoxicity. Accumulation of lipids in the skeletal muscle is associated with insulin resistance, but the majority of previous studies do not prove any causality. Most studies agree that it is not the intramuscular lipids per se that causes insulin resistance, but rather lipid intermediates such as diacylglycerols, fatty acyl-CoAs and ceramides and that it is the localization, composition and turnover of these intermediates that play an important role in the development of insulin resistance and T2D...
February 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/27913584/nitro-fatty-acid-pharmacokinetics-in-the-adipose-tissue-compartment
#18
Marco Fazzari, Nicholas K H Khoo, Steven R Woodcock, Diane K Jorkasky, Lihua Li, Francisco J Schopfer, Bruce A Freeman
Electrophilic nitro-fatty acids (NO2-FAs) promote adaptive and anti-inflammatory cell signaling responses as a result of an electrophilic character that supports post-translational protein modifications. A unique pharmacokinetic profile is expected for NO2-FAs because of an ability to undergo reversible reactions including Michael additions with biological cysteine-containing proteins and esterification into complex lipids. Herein we report via quantitative whole-body autoradiography analysis of rats gavaged with radiolabeled 10-nitro-[14C]oleic acid, preferential accumulation in adipose tissue over two weeks...
December 2, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27913180/structure-activity-and-in-vivo-evaluation-of-a-novel-lipoprotein-lipase-lpl-activator
#19
Werner J Geldenhuys, Joel Caporoso, Thomas C Leeper, Yoon-Kwang Lee, Li Lin, Altaf S Darvesh, Prabodh Sadana
Elevated triglycerides (TG) contribute towards increased risk for cardiovascular disease. Lipoprotein lipase (LPL) is an enzyme that is responsible for the metabolism of core triglycerides of very-low density lipoproteins (VLDL) and chylomicrons in the vasculature. In this study, we explored the structure-activity relationships of our lead compound (C10d) that we have previously identified as an LPL agonist. We found that the cyclopropyl moiety of C10d is not absolutely necessary for LPL activity. Several substitutions were found to result in loss of LPL activity...
November 21, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27912756/mechanisms-of-inflammatory-responses-and-development-of-insulin-resistance-how-are-they-interlinked
#20
Kanwal Rehman, Muhammad Sajid Hamid Akash
BACKGROUND: Insulin resistance (IR) is one of the major hallmark for pathogenesis and etiology of type 2 diabetes mellitus (T2DM). IR is directly interlinked with various inflammatory responses which play crucial role in the development of IR. Inflammatory responses play a crucial role in the pathogenesis and development of IR which is one of the main causative factor for the etiology of T2DM. METHODS: A comprehensive online English literature was searched using various electronic search databases...
December 3, 2016: Journal of Biomedical Science
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