New fluorogenic probes for neutral and alkaline ceramidases [Methods]
New fluorogenic ceramidase substrates derived from the N-acyl modification of our previously reported probes (RBM14) are reported. While none of the new probes were superior to the known RBM14C12 as acid ceramidase substrates, the corresponding nervonic acid amide (RBM14C24:1) is an efficient and selective substrate for the recombinant human neutral ceramidase, both in cell lysates and in intact cells. A second generation of substrates, incorporating the natural 2-(N-acylamino)-1,3-diol-4-ene framework (compounds RBM15) is also reported. Among them, the corresponding fatty acyl amides with an unsaturated N-acyl chain can b...
Source: The Journal of Lipid Research - May 31, 2019 Category: Lipidology Authors: Casasampere, M., Bielsa, N., Riba, D., Bassas, L., Xu, R., Mao, C., Fabrias, G., Abad, J.-L., Delgado, A., Casas, J. Tags: Methods Source Type: research
Quantitative metabolic profiling of urinary eicosanoids for clinical phenotyping [Methods]
The eicosanoids are a family of lipid mediators of pain and inflammation involved in multiple pathologies, including asthma, hypertension, cancer, atherosclerosis, and neurodegenerative diseases. These signaling mediators act locally, but are rapidly metabolized and transported to the systemic circulation as a mixture of primary and secondary metabolites. Accordingly, urine has become a useful readily accessible biofluid for monitoring the endogenous synthesis of these molecules. Herein, we present the validation of a rapid, repeatable, and precise method for the extraction and quantification of 32 eicosanoid urinary metab...
Source: The Journal of Lipid Research - May 31, 2019 Category: Lipidology Authors: Gomez, C., Gonzalez-Riano, C., Barbas, C., Kolmert, J., Hyung Ryu, M., Carlsten, C., Dahlen, S.-E., Wheelock, C. E. Tags: Methods Source Type: research
n-3 PUFAs improve erythrocyte fatty acid profile in patients with small AAA: a randomized controlled trial [Patient-Oriented and Epidemiological Research]
Abdominal aortic aneurysm (AAA) is an important cause of death in older adults, which has no current drug therapy. Inflammation and abnormal redox status are believed to be key pathogenic mechanisms for AAA. In light of evidence correlating inflammation with aberrant fatty acid profiles, this study compared erythrocyte fatty acid content in 43 AAA patients (diameter 3.0–4.5 cm) and 52 healthy controls. In addition, the effect of omega-3 PUFA (n-3 PUFA) supplementation on erythrocyte fatty acid content was examined in a cohort of 30 AAA patients as part of a 12 week randomized placebo-controlled clinical trial. Blood ...
Source: The Journal of Lipid Research - May 31, 2019 Category: Lipidology Authors: Meital, L. T., Windsor, M. T., Ramirez Jewell, R. M. L., Young, P., Schulze, K., Magee, R., ODonnell, J., Jha, P., Perissiou, M., Golledge, J., Bailey, T. G., Brooks, P., Askew, C. D., Russell, F. D. Tags: Patient-Oriented and Epidemiological Research Source Type: research
PCSK7 gene variation bridges atherogenic dyslipidemia with hepatic inflammation in NAFLD patients [Patient-Oriented and Epidemiological Research]
In conclusion, PCSK7 gene variation is associated with dyslipidemia and more severe liver disease in high risk individuals, likely by modulating PCSK7 expression/activity. (Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - May 31, 2019 Category: Lipidology Authors: Dongiovanni, P., Meroni, M., Baselli, G., Mancina, R. M., Ruscica, M., Longo, M., Rametta, R., Cespiati, A., Pelusi, S., Ferri, N., Ranzani, V., Nobili, V., Pihlajamaki, J., Fracanzani, A. L., Badiali, S., Petta, S., Fargion, S., Romeo, S., Kozlitina, J., Tags: Patient-Oriented and Epidemiological Research Source Type: research
Metabolomic correlates of central adiposity and earlier-life body mass index [Patient-Oriented and Epidemiological Research]
BMI is correlated with circulating metabolites, but few studies discuss other adiposity measures, and little is known about metabolomic correlates of BMI from early life. We investigated associations between different adiposity measures, BMI from childhood through adulthood, and metabolites quantified from serum using 1H NMR spectroscopy in 900 British men and women aged 60–64. We assessed BMI, waist-to-hip ratio (WHR), android-to-gynoid fat ratio (AGR), and BMI from childhood through adulthood. Linear regression with Bonferroni adjustment was performed to assess adiposity and metabolites. Of 233 metabolites, 168; 12...
Source: The Journal of Lipid Research - May 31, 2019 Category: Lipidology Authors: Wulaningsih, W., Proitsi, P., Wong, A., Kuh, D., Hardy, R. Tags: Patient-Oriented and Epidemiological Research Source Type: research
Uptake and metabolism of {beta}-apo-8'-carotenal, {beta}-apo-10'-carotenal, and {beta}-apo-13-carotenone in Caco-2 cells [Research Articles]
β-Apocarotenoids are eccentric cleavage products of carotenoids formed by chemical and enzymatic oxidations. They occur in foods containing carotenoids and thus might be directly absorbed from the diet. However, there is limited information about their intestinal absorption. The present research examined the kinetics of uptake and metabolism of β-apocarotenoids. Caco-2 cells were grown on 6-well plastic plates until a differentiated cell monolayer was achieved. β-Apocarotenoids were prepared in Tween 40 micelles, delivered to differentiated cells in serum-free medium, and incubated at 37°C for up to 8 h....
Source: The Journal of Lipid Research - May 31, 2019 Category: Lipidology Authors: Durojaye, B. O., Riedl, K. M., Curley, R. W., Harrison, E. H. Tags: Research Articles Source Type: research
The triglyceride synthesis enzymes DGAT1 and DGAT2 have distinct and overlapping functions in adipocytes [Research Articles]
Mammals store metabolic energy as triacylglycerols (TGs) in adipose tissue. TG synthesis is catalyzed by the evolutionarily unrelated acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes DGAT1 and DGAT2, which catalyze the same reaction and account for nearly all TG synthesis. The reasons for their convergent evolution to synthesize TGs remain unclear. Mice lacking DGAT1 are viable with reduced fat stores of TGs, whereas DGAT2 KO mice die postnatally just after birth with >90% reduction of TGs, suggesting that DGAT2 is the predominant enzyme for TG storage. To better understand the functional differences between the D...
Source: The Journal of Lipid Research - May 31, 2019 Category: Lipidology Authors: Chitraju, C., Walther, T. C., Farese, R. V. Tags: Research Articles Source Type: research
Membrane lipids and their degradation compounds control GM2 catabolism at intralysosomal luminal vesicles [Research Articles]
The catabolism of ganglioside GM2 is dependent on three gene products. Mutations in any of these genes result in a different type of GM2 gangliosidosis (Tay-Sachs disease, Sandhoff disease, and the B1 and AB variants of GM2 gangliosidosis), with GM2 as the major lysosomal storage compound. GM2 is also a secondary storage compound in lysosomal storage diseases such as Niemann-Pick disease types A–C, with primary storage of SM in type A and cholesterol in types B and C, respectively. The reconstitution of GM2 catabolism at liposomal surfaces carrying GM2 revealed that incorporating lipids into the GM2-carrying membrane...
Source: The Journal of Lipid Research - May 31, 2019 Category: Lipidology Authors: Anheuser, S., Breiden, B., Sandhoff, K. Tags: Research Articles Source Type: research
StarD5: an ER stress protein regulates plasma membrane and intracellular cholesterol homeostasis [Research Articles]
How plasma membrane (PM) cholesterol is controlled is poorly understood. Ablation of the gene encoding the ER stress steroidogenic acute regulatory-related lipid transfer domain (StarD)5 leads to a decrease in PM cholesterol content, a decrease in cholesterol efflux, and an increase in intracellular neutral lipid accumulation in macrophages, the major cell type that expresses StarD5. ER stress increases StarD5 expression in mouse hepatocytes, which results in an increase in accessible PM cholesterol in WT but not in StarD5–/– hepatocytes. StarD5–/– mice store higher levels of cholesterol and triglyc...
Source: The Journal of Lipid Research - May 31, 2019 Category: Lipidology Authors: Rodriguez-Agudo, D., Malacrida, L., Kakiyama, G., Sparrer, T., Fortes, C., Maceyka, M., Subler, M. A., Windle, J. J., Gratton, E., Pandak, W. M., Gil, G. Tags: Research Articles Source Type: research
Acid ceramidase promotes drug resistance in acute myeloid leukemia through NF-{kappa}B-dependent P-glycoprotein upregulation [Research Articles]
Acute myeloid leukemia (AML) is the most common acute leukemia in adults. More than half of older AML patients fail to respond to cytotoxic chemotherapy, and most responders relapse with drug-resistant disease. Failure to achieve complete remission can be partly attributed to the drug resistance advantage of AML blasts that frequently express P-glycoprotein (P-gp), an ATP-binding cassette transporter. Our previous work showed that elevated acid ceramidase (AC) levels in AML contribute to blast survival. Here, we investigated P-gp expression levels in AML relative to AC. Using parental HL-60 cells and drug-resistant derivat...
Source: The Journal of Lipid Research - May 31, 2019 Category: Lipidology Authors: Tan, S.-F., Dunton, W., Liu, X., Fox, T. E., Morad, S. A. F., Desai, D., Doi, K., Conaway, M. R., Amin, S., Claxton, D. F., Wang, H.-G., Kester, M., Cabot, M. C., Feith, D. J., Loughran, T. P. Tags: Research Articles Source Type: research
PNPLA2 influences secretion of triglyceride-rich lipoproteins by human hepatoma cells [Research Articles]
In conclusion, PNPLA2 influences TRL secretion, but is not involved in lipid-droplet homeostasis in human hepatoma cells, a physiological role that is quite distinct from the metabolic function of PNPLA2 in nonhepatic tissues. (Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - May 31, 2019 Category: Lipidology Authors: Taxiarchis, A., Mahdessian, H., Silveira, A., Fisher, R. M., vant Hooft, F. M. Tags: Research Articles Source Type: research
Building bridges: PCSK7 as a NAFLD candidate gene connecting hepatic inflammation with hypertriglyceridemia [Commentary]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - May 31, 2019 Category: Lipidology Authors: Carr, R. M., Davidson, N. O. Tags: Commentary Source Type: research
Erratum: The impact of PI 5-phosphatases on phosphoinositides in cell function and human disease [Errata]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - April 30, 2019 Category: Lipidology Authors: Ramos, A. R., Ghosh, S., Erneux, C. Tags: Errata Source Type: research
Acylation derivatization based LC-MS analysis of 25-hydroxyvitamin D from finger-prick blood [Methods]
Vitamin D metabolite analysis possessed significant clinical value for the pediatric department. However, invasive venipuncture sampling and high blood consumption inflicted much suffering on patients. For alleviation, we carried out a LC-MS method for 25-hydroxyvitamin D quantification in only 3 μl of plasma from the considerably less invasive finger-prick blood samples. To improve sensitivity, acylation on C3-hydroxyl (by isonicotinoyl chloride) rather than Diels-Alder adduction on s-cis-diene structure was for the very first time introduced into vitamin D metabolite derivatization. Compared with the existing derivati...
Source: The Journal of Lipid Research - April 30, 2019 Category: Lipidology Authors: Le, J., Yuan, T.-F., Geng, J.-Q., Wang, S.-T., Li, Y., Zhang, B.-H. Tags: Methods Source Type: research
Plasma lipoprotein-X quantification on filipin-stained gels: monitoring recombinant LCAT treatment ex vivo [Methods]
Familial LCAT deficiency (FLD) patients accumulate lipoprotein-X (LP-X), an abnormal nephrotoxic lipoprotein enriched in free cholesterol (FC). The low neutral lipid content of LP-X limits the ability to detect it after separation by lipoprotein electrophoresis and staining with Sudan Black or other neutral lipid stains. A sensitive and accurate method for quantitating LP-X would be useful to examine the relationship between plasma LP-X and renal disease progression in FLD patients and could also serve as a biomarker for monitoring recombinant human LCAT (rhLCAT) therapy. Plasma lipoproteins were separated by agarose gel e...
Source: The Journal of Lipid Research - April 30, 2019 Category: Lipidology Authors: Freeman, L. A., Shamburek, R. D., Sampson, M. L., Neufeld, E. B., Sato, M., Karathanasis, S. K., Remaley, A. T. Tags: Methods Source Type: research
