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Journal of Lipid Research

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https://www.readbyqxmd.com/read/28336574/switching-head-group-selectivity-in-mammalian-sphingolipid-biosynthesis-by-active-site-engineering-of-sphingomyelin-synthases
#1
Matthijs Kol, Radhakrishnan Panatala, Mirjana Nordmann, Leoni Swart, Leonie Van Suijlekom, Birol Cabukusta, Angelika Hilderink, Tanja Gabrietz, John G M Mina, Pentti Somerharju, Sergei Korneev, Fikadu G Tafesse, Joost C M Holthuis
Sphingomyelin (SM) is a fundamental component of mammalian cell membranes that contributes to mechanical stability, signaling and sorting. Its production involves the transfer of phosphocholine from phosphatidylcholine onto ceramide, a reaction catalyzed by SM synthase SMS1 in the Golgi and SMS2 at the plasma membrane. Mammalian cells also synthesize trace amounts of the SM analog ceramide phosphoethanolamine (CPE), but the physiological relevance of CPE production is unclear. Previous work revealed that SMS2 is a bifunctional enzyme producing both SM and CPE whereas a closely related enzyme, SMSr/SAMD8, acts as a monofunctional CPE synthase in the ER...
March 23, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28331000/biophysical-studies-of-cholesterol-effects-on-chromatin
#2
Isabel T G Silva, Vinicius Fernandes, Caio Souza, Werner Treptow, Guilherme Martins Santos
Changes in chromatin structure regulate gene expression and genome maintenance. Molecules that bind to the nucleosome, the complex of DNA and histone proteins, are key modulators of chromatin structure. Previous work indicated that cholesterol, a ubiquitous cellular lipid, may bind to chromatin in vivo, suggesting a potential function for lipids in modulating chromatin architecture. However, the molecular mechanisms of cholesterol action on chromatin structure have remained unclear. Here, we explored the biophysical impact of cholesterol on nucleosome and chromatin fibers reconstituted in vitro and characterized in silico the cholesterol binding to nucleosome...
March 22, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28314860/a-newborn-screening-method-for-cerebrotendinous-xanthomatosis-using-bile-alcohol-glucuronides-and-metabolite-ratios
#3
Frédéric M Vaz, Albert H Bootsma, Willem Kulik, Aad Verrips, Ron A Wevers, Peter C Schielen, Andrea E DeBarber, Hidde H Huidekoper
Cerebrotendinous xanthomatosis (CTX) is a treatable neurodegenerative metabolic disorder of bile acid synthesis where symptoms can be prevented if treatment with chenodeoxycholic acid supplementation is initiated early in life, making CTX an excellent candidate for newborn screening. We developed a new dried blood spot screening assay for this disorder based on different ratios between the accumulating cholestanetetrol glucuronide (tetrol) and specific bile acids/bile acid intermediates, without the need for derivatization...
March 17, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28314859/effects-of-cetp-inhibition-with-anacetrapib-on-metabolism-of-vldl-tg-and-plasma-apolipoproteins-c-ii-c-iii-and-e
#4
John S Millar, Michael E Lassman, Tiffany Thomas, Rajasekhar Ramakrishnan, Patricia Jumes, Richard L Dunbar, Emile M deGoma, Amanda L Baer, Wahida Karmally, Daniel S Donovan, Hashmi Rafeek, John A Wagner, Stephen Holleran, Joseph Obunike, Yang Liu, Soumia Aoujil, Taylor Standiford, David E Gutstein, Henry N Ginsberg, Daniel J Rader, Gissette Reyes-Soffer
Cholesteryl ester transfer protein (CETP) mediates the transfer of HDL cholesteryl esters(CE) for TG in VLDL/LDL. CETP inhibition, with anacetrapib, increases HDL-cholesterol(C), reduces LDL-C and lowers TG levels. This study describes the mechanisms responsible for TG lowering by examining the kinetics of VLDL-TG and apolipoproteins (apo) C-II, C-III, and E. Hypercholesterolemic subjects were randomized to either placebo(N=10) or atorvastatin 20 mg/qd(N=29) for 4 weeks(period 1) followed by 8-weeks of anacetrapib, 100 mg/qd(period 2)...
March 17, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28314858/identification-and-characterization-of-a-20%C3%AE-hydroxysteroid-dehydrogenase-from-the-anaerobic-gut-bacterium-butyricicoccus-desmolans-atcc-43058
#5
Saravanan Devendran, Celia Méndez-Garcia, Jason M Ridlon
Members of the gastrointestinal microbiota are known to convert glucocorticoids to androstanes, which can be subsequently converted to potent androgens by other members of the gut microbiota or host tissues. Butyricicoccus desmolans and Clostridium cadaveris has previously been reported for steroid-17,20-desmolase and 20β-hydroxysteroid dehydrogenase (20β-HSDH) activities that were responsible for androstane formation from cortisol, however the gene encoding these enzymes has yet to be reported. In this work, we identified and located a gene encoding 20β-HSDH in both B...
March 17, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28298293/discovery-and-fine-mapping-of-loci-associated-with-monounsaturated-fatty-acids-through-trans-ethnic-meta-analysis-in-chinese-and-european-populations
#6
Yao Hu, Toshiko Tanaka, Jingwen Zhu, Weihua Guan, Jason H Y Wu, Bruce M Psaty, Barbara McKnight, Irena B King, Qi Sun, Melissa Richard, Ani Manichaikul, Alexis C Frazier-Wood, Edmond K Kabagambe, Paul N Hopkins, Jose M Ordovas, Luigi Ferrucci, Stefania Bandinelli, Donna K Arnett, Yii-Der I Chen, Shuang Liang, David S Siscovick, Michael Y Tsai, Stephen S Rich, Myriam Fornage, Frank B Hu, Eric B Rimm, Majken K Jensen, Rozenn N Lemaitre, Dariush Mozaffarian, Lyn M Steffen, Andrew P Morris, Huaixing Li, Xu Lin
Monounsaturated fatty acids (MUFAs) are unsaturated fatty acids with one double bond and are derived from endogenous synthesis and dietary intake. Accumulating evidence has suggested that plasma and erythrocyte MUFA levels were associated with cardiometabolic disorders including cardiovascular disease (CVD), type 2 diabetes (T2D) and metabolic syndrome (MS). Previous genome-wide association studies (GWAS) have identified seven loci for plasma and erythrocyte palmitoleic acid and oleic acid levels in populations of European origin...
March 15, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28298292/cellular-cholesterol-homeostasis-in-alzheimer-s-disease
#7
Ta Yuan Chang, Yoshio Yamauchi, Mazahir Hasan, Catherine Cy Chang
Alzheimer's disease [AD] is the most common form of dementia in older adults. Currently, there is no cure for AD. The hallmark of AD is the accumulation of extracellular amyloid plaques composed of amyloid beta peptides [Abeta; especially Abeta1-42], and neurofibrillary tangles, composed of hyper-phosphorylated tau, accompanied with chronic neuroinflammation. Abeta are derived from the amyloid precursor protein APP. The oligomeric form of Abeta is probably the most neurotoxic species; its accumulation eventually forms the insoluble and aggregated amyloid plaques...
March 15, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28292942/the-apoe-receptors-vldlr-and-apoer2-in-central-nervous-system-function-and-disease
#8
Courtney Lane-Donovan, Joachim Herz
The low-density lipoprotein receptor (LDLR) family has long been studied for its role in cholesterol transport and metabolism; however, the identification of apolipoprotein E4 (ApoE4), an LDLR ligand, as a genetic risk factor for late-onset Alzheimers disease (AD) has focused attention on the role this receptor family plays in the central nervous system (CNS). Surprisingly, it was discovered that two LDLR family members, Apolipoprotein E receptor 2 (Apoer2) and very-low-density lipoprotein receptor (Vldlr), play key roles in brain development and adult synaptic plasticity, primarily by mediating Reelin signaling...
March 14, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28283530/identification-of-enzymes-involved-in-oxidation-of-phenylbutyrate
#9
Neža Palir, Jos P N Ruiter, Ronald J A Wanders, Riekelt H Houtkooper
In recent years the short-chain fatty acid 4-phenylbutyrate (PB) has emerged as a promising drug for various clinical conditions. In fact, PB is FDA-approved for urea cycle disorders since 1996. PB is more potent and less toxic than its metabolite phenylacetate (PA), and not just a pro-drug for PA as it was initially assumed. The metabolic pathway of PB, however, has remained unclear. Therefore, we set out to identify the enzymes involved in the β-oxidation of PB. We used cells deficient in specific steps of fatty acid β-oxidation, and used ultra-high performance liquid chromatography (UHPLC) to measure to which enzymes are able to convert PB or its downstream products...
March 9, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28280112/lipidomic-characterization-and-localization-of-phospholipids-in-the-human-lung
#10
Karin A Zemski Berry, Robert C Murphy, Beata Kosmider, Robert J Mason
Lipids play a central role in lung physiology and pathology, however a comprehensive lipidomic characterization of human pulmonary cells relevant to disease has not been performed. The cells involved in lung host defense, including alveolar macrophages (AM), bronchial epithelial cells (BEC), and alveolar type II cells (ATII), were isolated from human subjects and lipidomic analysis by LC-MS and LC-MS/MS was performed. Additionally, pieces of lung tissue from the same donors were analyzed by MALDI imaging mass spectrometry (IMS) in order to determine lipid localization in the tissue...
March 9, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28274961/lipid-and-lipoprotein-abnormalities-in-acute-lymphoblastic-leukemia-survivors
#11
Sophia Morel, Jade Leahy, Maryse Fournier, Benoit Lamarche, Carole Garofalo, Guy Grimard, Floriane Poulain, Edgard Delvin, Caroline Laverdière, Maja Krajinovic, Simon Drouin, Daniel Sinnett, Valérie Marcil, Emile Levy
Survivors of acute lymphoblastic leukemia (ALL), the most common cancer in children, are at increased risk of developing late cardiometabolic conditions. However, the mechanisms are not fully understood. The study aimed to characterize plasma lipid profile, Apolipoprotein (Apo) distribution and lipoprotein composition of 80 childhood ALL survivors compared to 22 healthy controls. Our results show that, despite their young age, 50% of the ALL survivors displayed dyslipidemia, characterized by increased plasma TG and LDL-cholesterol, as well as decreased HDL-cholesterol...
March 8, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28264880/therapeutic-potential-of-nuclear-receptor-agonists-in-alzheimer-s-disease
#12
Miguel Moutinho, Gary E Landreth
The Alzheimer's disease (AD) is characterized by an extensive accumulation of amyloid-β (Aβ) peptide, which triggers a set of deleterious processes including synaptic dysfunction, inflammation and neuronal injury leading to neuronal loss and cognitive impairment. A large body of evidence supports that nuclear receptor (NR) activation could be a promising therapeutic approach for AD. NRs are ligand-activated transcription factors that regulate gene expression and have a cell type-specific effects. In this review we discuss the mechanisms that underlie the beneficial effects of NRs in AD...
March 6, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28264879/abcg1-regulates-pulmonary-surfactant-metabolism-in-mice-and-men
#13
Thomas Q de Aguiar Vallim, Elinor Lee, David J Merriott, Christopher N Goulbourne, Joan Cheng, Angela Cheng, Ayelet Gonen, Ryan M Allen, Elisa N D Palladino, David A Ford, Tisha Wang, Ángel Baldán, Elizabeth J Tarling
Idiopathic pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by accumulation of surfactant. Surfactant synthesis and secretion are restricted to epithelial type 2 pneumocytes (T2 cells). Clearance of surfactant is dependent upon T2 cells and macrophages. ATP Binding Cassette Transporter G1 (ABCG1) is highly expressed in both T2 cells and macrophages. ABCG1-deficient mice accumulate surfactant, lamellar body-loaded T2 cells, lipid-loaded macrophages, B-1 lymphocytes and immunoglobulins, clearly demonstrating ABCG1 has a critical role in pulmonary homeostasis...
March 6, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28258089/oncostatin-m-receptor-%C3%AE-deficiency-attenuates-atherogenesis-by-inhibiting-jak2-stat3-signaling-in-macrophages
#14
Xin Zhang, Jing Li, Juan-Juan Qin, Wen-Lin Cheng, Xueyong Zhu, Fu-Han Gong, Zhigang She, Zan Huang, Hao Xia, Hongliang Li
Oncostatin M (OSM) is a secreted cytokine mainly involved in chronic inflammatory and cardiovascular diseases through binding to OSM receptor β(OSMR-β). Recent studies demonstrated that the presence of OSM contributed to the destabilization of atherosclerotic plaque. To investigate whether OSMR-β deficiency affects atherosclerosis, male OSMR-β-/-ApoE-/- mice were generated and utilized. Here we observed OSMR-β expression was remarkably up-regulated in both human and mouse atherosclerotic lesions, which was mainly located in macrophages...
March 3, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28258088/apoe-and-lipid-homeostasis-in-alzheimer-s-disease
#15
Ta-Yuan Chang, Catherine C Y Chang
Introduction to thematic review series on ApoE and lipid homeostasis in Alzheimer's disease.
March 2, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28258087/the-role-of-apoe-on-lipid-homeostasis-and-inflammation-in-normal-brains
#16
George William Rebeck
The role of APOE in the risk of Alzheimers disease has largely focused on its effects on AD pathological processes. However, there are increasing data that APOE genotype affects processes in normal brains. Studies of young, cognitively normal humans show effects of APOE genotype on brain structure and activity. Studies of normal APOE knock-in mice show effects of APOE genotype on brain structure, neuronal markers, and behavior. APOE interactions with molecules important for lipid efflux and lipid endocytosis underlie effects of APOE genotype on neuroinflammation and lipoprotein composition...
March 2, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28250026/foxo3-increases-mir-34a-to-cause-palmitate-induced-cholangiocyte-lipoapoptosis
#17
Sathish Kumar Natarajan, Bailey A Stringham, Ashley M Mohr, Cody J Wehrkamp, Sizhao Lu, Mary Anne Phillippi, Dee Harrison-Findik, Justin L Mott
Non-alcoholic steatohepatitis (NASH) patients have elevated plasma saturated free fatty acid levels. These toxic fatty acids can induce liver cell death and our recent results demonstrated that the biliary epithelium may be susceptible to lipotoxicity. Here, we explored the molecular mechanisms of cholangiocyte lipoapoptosis in cell culture and in an animal model of NASH. Treatment of cholangiocytes with palmitate showed increased caspase-3/7 activity, and increased levels of cleaved PARP and cleaved caspase 3 demonstrating cholangiocyte lipoapoptosis...
March 1, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28250025/synthesis-of-apo-13-and-apo-15-lycopenoids-cleavage-products-of-lycopene-that-are-retinoic-acid-antagonists
#18
Sureshbabu Narayanasamy, Jian Sun, Ryan E Pavlovicz, Abdulkerim Eroglu, Cassandra E Rush, Benjamin D Sunkel, Chenglong Li, Earl H Harrison, Robert W Curley
Consumption of the tomato carotenoid, lycopene, has been associated with favorable health benefits. Some of lycopenes biological activity may be due to metabolites resulting from cleavage of the lycopene molecule. Because of their structural similarity to the retinoic acid receptor antagonist beta-apo-13-carotenone, the first half putative oxidative cleavage products of the symmetrical lycopene have been synthesized. All transformations proceed in moderate to good yield and some with high stereochemical integrity allowing ready access to these otherwise difficult to obtain terpenoids...
March 1, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28246337/diacylglycerol-kinase-%C3%AF%C2%B5-deficiency-preserves-glucose-tolerance-and-modulates-lipid-metabolism-in-obese-mice
#19
Louise Mannerås-Holm, Milena Schönke, Joseph T Brozinick, Laurène Vetterli, Hai-Hoang Bui, Philip Sanders, Emmani B M Nascimento, Marie Björnholm, Alexander V Chibalin, Juleen R Zierath
Diacylglycerol kinases (DGKs) catalyze the phosphorylation and conversion of DAG into phosphatidic acid. DGK isozymes have unique primary structures, expression patterns, subcellular localizations, regulatory mechanisms and DAG preferences. DGKε has a hydrophobic segment that promotes its attachment to membranes and shows substrate specificity for DAG with an arachidonoyl acyl chain in the sn-2 position of the substrate. We determined the role of DGKε in the regulation of energy and glucose homeostasis in relation to diet-induced insulin resistance and obesity using DGKε deficient (KO) and wild-type mice...
February 28, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28246336/apolipoprotein-e-and-alzheimer-disease-the-influence-of-apoe-on-amyloid-%C3%AE-and-other-amyloidogenic-proteins
#20
Tien-Phat V Huynh, Albert A Davis, Jason D Ulrich, David M Holtzman
Alzheimer disease (AD) is one of the fastest-growing causes of death and disability in persons 65 years or older, affecting more than 5 million Americans alone. Clinical manifestations of AD include progressive decline in memory, executive function, language, and other cognitive domains. Research efforts within the last three decades have identified the apolipoprotein E gene (APOE) as the most significant genetic risk factor for late-onset AD, which accounts for >99% of cases. The apoE protein is hypothesized to affect AD pathogenesis through a variety of mechanisms, from its effects on the blood brain barrier, the innate immune system, synaptic function, to the accumulation of amyloid-β (Aβ)...
February 27, 2017: Journal of Lipid Research
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