journal
https://read.qxmd.com/read/38417553/mining-cholesterol-genes-from-thousands-of-mouse-livers-identifies-aldolase-c-as-a-regulator-of-cholesterol-biosynthesis
#1
JOURNAL ARTICLE
James A Votava, Steven V John, Zhonggang Li, Shuyang Chen, Jing Fan, Brian W Parks
The availability of genome-wide transcriptomic and proteomic datasets is ever-increasing and often not used beyond initial publication. Here, we applied module-based co-expression network analysis to a comprehensive catalog of 35 mouse genome-wide liver expression datasets (encompassing more than 3800 mice) with the goal of identifying and validating unknown genes involved in cholesterol metabolism. From these 35 datasets, we identified a conserved module of genes enriched with cholesterol biosynthetic genes...
February 26, 2024: Journal of Lipid Research
https://read.qxmd.com/read/38373655/pcsk9-vaccines-a-promising-new-strategy-for-the-treatment-of-hypercholesterolemia
#2
JOURNAL ARTICLE
Bryce Chackerian, Alan T Remaley
No abstract text is available yet for this article.
February 17, 2024: Journal of Lipid Research
https://read.qxmd.com/read/38369184/a-fluorogenic-substrate-for-the-detection-of-lipid-amidases-in-intact-cells
#3
JOURNAL ARTICLE
Mireia Casasampere, Johnson Ung, Alejandro Iñáñez, Carine Duffau, Kazuhito Tsuboi, Josefina Casas, Su-Fern Tan, David J Feith, Nathalie Andrieu-Abadie, Bruno Segui, Thomas P Loughran, José Luis Abad, Gemma Fabrias
Lipid amidases of therapeutic relevance include acid ceramidase (AC), N-acylethanolamine-hydrolyzing acid amidase (NAAA) and fatty acid amide hydrolase (FAAH). Although fluorogenic substrates have been developed for the three enzymes and high throughput methods for screening have been reported, a platform for the specific detection of these enzyme activities in intact cells is lacking. In this article we report on the coumarinic 1-deoxydihydroceramide RBM1-151, a 1-deoxy derivative and vinilog of RBM14-C12, as a novel substrate of amidases...
February 16, 2024: Journal of Lipid Research
https://read.qxmd.com/read/38354857/decreased-sarcoplasmic-reticulum-phospholipids-in-human-skeletal-muscle-are-associated-with-metabolic-syndrome
#4
JOURNAL ARTICLE
Samantha E Adamson, Sangeeta Adak, Max C Petersen, Dustin Higgins, Larry D Spears, Rong Mei Zhang, Andrea Cedeno, Alexis McKee, Aswathi Kumar, Sudhir Singh, Fong-Fu Hsu, Janet B McGill, Clay F Semenkovich
Metabolic syndrome affects more than one in three adults and is associated with increased risk of diabetes, cardiovascular disease, and all-cause mortality. Muscle insulin resistance is a major contributor to the development of the metabolic syndrome. Studies in mice have linked skeletal muscle sarcoplasmic reticulum (SR) phospholipid composition to sarco/endoplasmic reticulum Ca2+ -ATPase (SERCA) activity and insulin sensitivity. To determine if the presence of metabolic syndrome alters specific phosphatidylcholine (PC) and phosphatidylethanolamine (PE) species in human sarcoplasmic reticulum (SR), we compared SR phospholipid composition in skeletal muscle from sedentary subjects with metabolic syndrome and sedentary control subjects without metabolic syndrome...
February 12, 2024: Journal of Lipid Research
https://read.qxmd.com/read/38342437/elovl4b-knockout-zebrafish-as-a-model-for-ocular-very-long-chain-polyunsaturated-fatty-acid-deficiency
#5
JOURNAL ARTICLE
Uzoamaka Nwagbo, Saba Parvez, J Alan Maschek, Paul S Bernstein
Very-long-chain polyunsaturated fatty acids (VLC-PUFAs) are a group of lipids with chain lengths >24 carbons, and the ELOVL4 enzyme is responsible for the rate-limiting step in vertebrate VLC-PUFA biosynthesis. Studies on the role of VLC-PUFAs in vision have been hindered due to the need for adequate animal models to capture the global loss of VLC-PUFAs. Since homozygous Elovl4 ablation is lethal in neonatal mice due to catastrophic drying from the loss of their protective skin barrier, we established a zebrafish model of Elovl4 ablation...
February 9, 2024: Journal of Lipid Research
https://read.qxmd.com/read/38342436/loss-of-function-and-reduced-levels-of-sphingolipid-desaturase-degs1-variants-are-both-relevant-in-disease-mechanism
#6
JOURNAL ARTICLE
Michele Dei Cas, Linda Montavoci, Claudia Pasini, Anna Caretti, Sara Penati, Carla Martinelli, Umberto Gianelli, Sara Casati, Francesca Nardecchia, Annalaura Torella, Nicola Brunetti-Pierri, Marco Trinchera
The last step of ex novo ceramide biosynthesis consists of the conversion of dihydroceramide into ceramide catalyzed by sphingolipid Δ4-desaturase DEGS1. DEGS1 variants were found to be responsible for heterogeneous clinical pictures belonging to the family of hypomyelinating leukodystrophies. To investigate the mechanisms making such variants pathogenic, we designed a procedure for the efficient detection of desaturase activity in vitro using LC-MS/MS and prepared a suitable cell model knocking-out DEGS1 in HEK-293T cells through CRISPR-Cas9 genome editing (KO-DES-HEK)...
February 9, 2024: Journal of Lipid Research
https://read.qxmd.com/read/38320654/plasma-c24-0-and-c26-0-lysophosphatidylcholines-are-reliable-biomarkers-for-the-diagnosis-of-peroxisomal-%C3%AE-oxidation-disorders
#7
JOURNAL ARTICLE
Blai Morales-Romero, José Manuel González de Aledo-Castillo, Cristina Fernández Sierra, Carmen Martínez Carreira, Carles Zaragoza Bonet, Rosa Fernández Bonifacio, Maria Antònia Caro Miró, Ana Argudo-Ramírez, Rosa María López Galera, Judit García-Villoria
The gold-standard diagnostic test for peroxisomal disorders (PDs) is plasma concentration analysis of very long-chain fatty acids (VLCFA). However, this method's time-consuming nature and limitations in cases which present normal VLCFA levels necessitates alternative approaches. The analysis of C26:0-lysophosphatydylcholine (C26:0-LPC) in dried blood spot samples by tandem-mass spectrometry (MS/MS) has successfully been implemented in certain newborn screening programs to diagnose X-linked adrenoleukodystrophy (ALD)...
February 4, 2024: Journal of Lipid Research
https://read.qxmd.com/read/38309418/evaluation-of-antisense-oligonucleotides-therapy-targeting-hsd17b13-in-a-fibrosis-mice-model
#8
JOURNAL ARTICLE
Yanling Ma, Hong Cai, Julia Smith, Ching-Hsuen Chu, Stephen E Mercer, Stephanie Boehm, Ivar Mcdonald, Bradley Zinker, Dong Cheng
OBJECTIVE: Human genetic evidence suggests a protective role of loss-of-function variants in 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13) for liver fibrotic diseases. Although there is limited preclinical experimental data on Hsd17b13 antisense oligonucleotide (ASO) or siRNA in a fibrosis model, several ASO and siRNA approaches are being tested clinically as potential therapies for non-alcoholic steatohepatitis (NASH).. The aim of this study was to assess the therapeutic potential of Hsd17b13 ASO in a preclinical advanced NASH-like hepatic fibrosis in vivo model...
February 1, 2024: Journal of Lipid Research
https://read.qxmd.com/read/38309417/geranylgeranyl-isoprenoids-and-hepatic-rap1a-regulate-basal-and-statin-induced-expression-of-pcsk9
#9
JOURNAL ARTICLE
Yating Wang, Brea Tinsley, Stefano Spolitu, John A Zadroga, Heena Agarwal, Amesh K Sarecha, Lale Ozcan
Low-density lipoprotein cholesterol (LDL-C) lowering is the main goal of atherosclerotic cardiovascular disease prevention, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition is now a validated therapeutic strategy that lowers serum LDL-C and reduces coronary events. Ironically, the most widely used medicine to lower cholesterol, statins, has been shown to increase circulating PCSK9 levels, which limits their efficacy. Here, we show that geranylgeranyl isoprenoids and hepatic Rap1a regulate both basal and statin induced expression of PCSK9 and contribute to LDL-C homeostasis...
February 1, 2024: Journal of Lipid Research
https://read.qxmd.com/read/38295986/pi-4-5-p-2-binding-sites-in-the-ebola-virus-matrix-protein-vp40-modulate-assembly-and-budding
#10
JOURNAL ARTICLE
Kristen A Johnson, Melissa R Budicini, Nisha Bhattarai, Tej Sharma, Sarah Urata, Bernard S Gerstman, Prem P Chapagain, Sheng Li, Robert V Stahelin
Ebolavirus (EBOV) causes severe hemorrhagic fever in humans and is lethal in a large percentage of those infected. The EBOV matrix protein VP40 is a peripheral binding protein that forms a shell beneath the lipid bilayer in virions and virus-like particles (VLPs). VP40 is required for virus assembly and budding from the host cell plasma membrane. VP40 is a dimer that can rearrange into oligomers at the plasma membrane interface, but it is unclear how these structures form and how they are stabilized. We therefore investigated the ability of VP40 to form stable oligomers using in vitro and cellular assays...
January 29, 2024: Journal of Lipid Research
https://read.qxmd.com/read/38295985/histone-demethylase-kdm1a-promotes-hepatic-steatosis-and-inflammation-by-increasing-chromatin-accessibility-in-nafld
#11
JOURNAL ARTICLE
Zifeng Yang, Siyao Zhang, Xiang Liu, Rui Shu, Wei Shi, Weiyi Qu, Dianyu Liu, Zhiwei Cai, Ye Wang, Xu Cheng, Yemao Liu, Xiao-Jing Zhang, Lan Bai, Hongliang Li, Zhi-Gang She
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease without specific FDA-approved drugs. Recent advances suggest that chromatin remodeling and epigenetic alteration contribute to the development of NAFLD. The functions of the corresponding molecular modulator in NAFLD, however, are still elusive. KDM1A, commonly known as LSD1 (lysine-specific histone demethylase 1), has been reported to increase glucose uptake in hepatocellular carcinoma. In addition, a recent study suggests that inhibition of KDM1A reduces lipid accumulation in primary brown adipocytes...
January 29, 2024: Journal of Lipid Research
https://read.qxmd.com/read/38295984/bacterial-lipopolysaccharide-forms-aggregates-with-apolipoproteins-in-male-and-female-rat-brains-after-ethanol-binges
#12
JOURNAL ARTICLE
L López-Valencia, M Moya, B Escudero, B García-Bueno, L Orio
Alcohol binge drinking allows the translocation of bacterial lipopolysaccharide (LPS) from the gut to the blood, which activates the peripheral immune system with consequences in neuroinflammation. A possible access/direct signaling of LPS to/in the brain has not yet been described under alcohol abuse conditions. Apolipoproteins are compounds altered by alcohol with high affinity to LPS which may be involved in its transport to the brain or in its elimination. Here, we explored the expression of small components of LPS, in its free form or bound to apolipoproteins, in the brain of female and male rats exposed to alcohol binges...
January 29, 2024: Journal of Lipid Research
https://read.qxmd.com/read/38286180/decoding-the-complexities-of-lipid-homeostasis-through-a-unified-mouse-genetic-resource
#13
EDITORIAL
Carlos Viesi, Marcus Seldin
No abstract text is available yet for this article.
January 27, 2024: Journal of Lipid Research
https://read.qxmd.com/read/38280459/nuclear-sphk2-s1p-signaling-is-a-key-regulator-of-apoe-production-and-a%C3%AE-uptake-in-astrocytes
#14
JOURNAL ARTICLE
Masato Komai, Yuka Noda, Atsuya Ikeda, Nanaka Kaneshiro, Yuji Kamikubo, Takashi Sakurai, Takashi Uehara, Nobumasa Takasugi
The link between changes in astrocyte function and the pathological progression of Alzheimer's disease (AD) has attracted considerable attention. Interestingly, activated astrocytes in AD show abnormalities in their lipid content and metabolism. In particular, the expression of ApoE, a lipid transporter, is decreased. Because ApoE has anti-inflammatory and amyloid β (Aβ)-metabolizing effects, the nuclear receptors, retinoid X receptor (RXR) and LXR, which are involved in ApoE expression, are considered promising therapeutic targets for AD...
January 25, 2024: Journal of Lipid Research
https://read.qxmd.com/read/38280458/glucosylceramide-flippases-contribute-to-cellular-glucosylceramide-homeostasis
#15
JOURNAL ARTICLE
Natsuki Kita, Asuka Hamamoto, Siddabasave Gowda B Gowda, Hiroyuki Takatsu, Kazuhisa Nakayama, Makoto Arita, Shu-Ping Hui, Hye-Won Shin
Lipid transport is an essential cellular process with importance to human health, disease development, and therapeutic strategies. Type IV P-type ATPases (P4-ATPases) have been identified as membrane lipid flippases by utilizing nitrobenzoxadiazole (NBD)-labeled lipids as substrates. Among the 14 human P4-ATPases, ATP10D was shown to flip NBD-glucosylceramide (GlcCer) across the plasma membrane. Here, we found that conversion of incorporated GlcCer (d18:1/12:0) to other sphingolipids is accelerated in cells exogenously expressing ATP10D but not its ATPase-deficient mutant...
January 25, 2024: Journal of Lipid Research
https://read.qxmd.com/read/38272356/the-role-of-n-terminus-phosphorylation-of-dgk-%C3%AE
#16
JOURNAL ARTICLE
Millie X Barbernitz, Lauren R Devine, Robert N Cole, Daniel M Raben
Diacylglycerol kinases (DGKs) are lipid kinases that mediate the phosphorylation of diacylglycerol (DAG) leading to the production of phosphatidic acid (PtdOH). To examine the role of phosphorylation on DGK-θ, we first identified the phosphorylated sites on endogenous DGK-θ from mouse brains and found four sites: S15, S17, which we refer to phosphomotif-1 sites, and S22 and S26 which we refer to as phosphomotif-2 sites. This study focused on the role of these phosphorylated sites on enzyme activity, membrane binding, thermal stability, and cellular half-life of DGK-θ...
January 23, 2024: Journal of Lipid Research
https://read.qxmd.com/read/38272355/finasteride-delays-atherosclerosis-progression-in-mice-and-is-associated-with-a-reduction-in-plasma-cholesterol-in-men
#17
JOURNAL ARTICLE
Patrick McQueen, Donald Molina, Ivan Pinos, Samuel Krug, Anna J Taylor, Michael R LaFrano, Maureen A Kane, Jaume Amengual
Finasteride is commonly prescribed to treat benign prostate hyperplasia and male-pattern baldness in cis men and, more recently, trans individuals. However, the effect of finasteride on cardiovascular disease remains elusive. We evaluated the role of finasteride on atherosclerosis using low-density lipoprotein (LDL) receptor-deficient (Ldlr-/- ) mice. Next, we examined the relevance to humans by analysing the data deposited between 2009 and 2016 in the National Health and Nutrition Examination Survey (NHANES)...
January 23, 2024: Journal of Lipid Research
https://read.qxmd.com/read/38246237/spatial-lipidomics-of-coronary-atherosclerotic-plaque-development-in-a-familial-hypercholesterolemia-swine-model
#18
JOURNAL ARTICLE
Nuria Slijkhuis, Francesca Razzi, Suze-Anne Korteland, Bram Heijs, Kim van Gaalen, Dirk J Duncker, Antonius F W van der Steen, Volkert van Steijn, Heleen M M van Beusekom, Gijs van Soest
Coronary atherosclerosis is caused by plaque build-up, with lipids playing a pivotal role in its progression. However, lipid composition and distribution within coronary atherosclerosis remain unknown. This study aims to characterize lipids and investigate differences in lipid composition across disease stages to aid in the understanding of disease progression. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was used to visualize lipid distributions in coronary artery sections (n=17) from hypercholesterolemic swine...
January 19, 2024: Journal of Lipid Research
https://read.qxmd.com/read/38246236/does-small-hdl-s-function-improve-when-lipid-lowering-alters-its-composition
#19
JOURNAL ARTICLE
Jay W Heinecke, Tomas Vaisar, Karin E Bornfeldt
No abstract text is available yet for this article.
January 19, 2024: Journal of Lipid Research
https://read.qxmd.com/read/38246235/changes-in-soluble-ldl-receptor-and-lipoprotein-fractions-in-response-to-diet-in-the-dietfits-weight-loss-study
#20
JOURNAL ARTICLE
Ronald M Krauss, Lois M Fisher, Sarah M King, Christopher D Gardner
Circulating levels of the soluble ligand binding ectodomain of the LDL receptor (sLDLR) that is proteolytically cleaved from the cell surface have been shown to correlate with plasma triglycerides, but the lipid and lipoprotein effects of longitudinal changes in sLDLR have not been examined. We sought to assess associations between changes in sLDLR and detailed lipoprotein measurements between baseline and six months in participants in the DIETFITS weight loss trial who were randomly assigned to the low-fat (n=225) or low-carbohydrate (n=236) diet arms...
January 19, 2024: Journal of Lipid Research
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