Liver-specific ceramide reduction alleviates steatosis and insulin resistance in alcohol-fed mice [Research Articles]
We examined effects of alcohol on hepatic lipid metabolism, body composition, energy homeostasis, and insulin sensitivity as measured by hyperinsulinemic-euglycemic clamp. Our results demonstrate that hepatic ceramide reduction ameliorates the effects of alcohol on hepatic lipid droplet (LD) accumulation by promoting VLDL secretion and lipophagy, the latter of which involves ceramide cross-talk between the lysosomal and LD compartments. We additionally demonstrate that hepatic ceramide reduction prevents alcohol’s inhibition of hepatic insulin signaling. These effects on the liver are associated with a reduction in o...
Source: The Journal of Lipid Research - June 30, 2020 Category: Lipidology Authors: Correnti, J., Lin, C., Brettschneider, J., Kuriakose, A., Jeon, S., Scorletti, E., Oranu, A., McIver-Jenkins, D., Kaneza, I., Buyco, D., Saiman, Y., Furth, E. E., Argemi, J., Bataller, R., Holland, W. L., Carr, R. M. Tags: Research Articles Source Type: research
Potential COVID-19 therapeutics from a rare disease: weaponizing lipid dysregulation to combat viral infectivity [Reviews]
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has resulted in the death of more than 328,000 persons worldwide in the first 5 months of 2020. Herculean efforts to rapidly design and produce vaccines and other antiviral interventions are ongoing. However, newly evolving viral mutations, the prospect of only temporary immunity, and a long path to regulatory approval pose significant challenges and call for a common, readily available, and inexpensive treatment. Strategic drug repurposing combined with rapid testing of established molecular targets could ...
Source: The Journal of Lipid Research - June 30, 2020 Category: Lipidology Authors: Sturley, S. L., Rajakumar, T., Hammond, N., Higaki, K., Marka, Z., Marka, S., Munkacsi, A. B. Tags: Reviews Source Type: research
The Ebola virus matrix protein VP40 hijacks the host plasma membrane to form virus envelope [Images In Lipid Research]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - June 30, 2020 Category: Lipidology Authors: Amiar, S., Stahelin, R. V. Tags: Images In Lipid Research Source Type: research
Opening ASBMB publications freely to all [Editorials]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - June 30, 2020 Category: Lipidology Authors: Gierasch, L. M., Davidson, N. O., Rye, K.-A., Burlingame, A. L. Tags: Editorials Source Type: research
A simple method for sphingolipid analysis of tissues embedded in optimal cutting temperature compound [Methods]
MS-assisted lipidomic tissue analysis is a valuable tool to assess sphingolipid metabolism dysfunction in disease. These analyses can reveal potential pharmacological targets or direct mechanistic studies to better understand the molecular underpinnings and influence of sphingolipid metabolism alterations on disease etiology. But procuring sufficient human tissues for adequately powered studies can be challenging. Therefore, biorepositories, which hold large collections of cryopreserved human tissues, are an ideal retrospective source of specimens. However, this resource has been vastly underutilized by lipid biologists, a...
Source: The Journal of Lipid Research - May 31, 2020 Category: Lipidology Authors: Rohrbach, T. D., Boyd, A. E., Grizzard, P. J., Spiegel, S., Allegood, J., Lima, S. Tags: Methods Source Type: research
A direct fluorometric activity assay for lipid kinases and phosphatases [Methods]
Lipid kinases and phosphatases play key roles in cell signaling and regulation, are implicated in many human diseases, and are thus attractive targets for drug development. Currently, no direct in vitro activity assay is available for these important enzymes, which hampers mechanistic studies as well as high-throughput screening of small molecule modulators. Here, we report a highly sensitive and quantitative assay employing a ratiometric fluorescence sensor that directly and specifically monitors the real-time concentration change of a single lipid species. Because of its modular design, the assay system can be applied to...
Source: The Journal of Lipid Research - May 31, 2020 Category: Lipidology Authors: Sun, J., Singaram, I., Soflaee, M. H., Cho, W. Tags: Methods Source Type: research
Serum nonesterified fatty acids have utility as dietary biomarkers of fat intake from fish, fish oil, and dairy in women [Methods]
Nutritional studies rely on various biological specimens for FA determination, yet it is unclear how levels of serum NEFAs correlate with other circulating lipid pools. Here, we used a high-throughput method (<4 min/sample) based on multisegment injection-nonaqueous capillary electrophoresis-mass spectrometry (MSI-NACE-MS) to investigate whether specific serum NEFAs have utility as biomarkers of dietary fat intake in women. We first identified circulating NEFAs correlated with long-term/habitual food intake among pregnant women with contrasting dietary patterns (n = 50). Acute changes in serum NEFA trajectories were als...
Source: The Journal of Lipid Research - May 31, 2020 Category: Lipidology Authors: Azab, S. M., de Souza, R. J., Teo, K. K., (for the FAMILY investigators), Anand, S. S., Williams, N. C., Holzschuher, J., McGlory, C., Philips, S. M., Britz-McKibbin, P. Tags: Methods Source Type: research
LDL subclass lipidomics in atherogenic dyslipidemia: effect of statin therapy on bioactive lipids and dense LDL [Patient-Oriented and Epidemiological Research]
Atherogenic LDL particles are physicochemically and metabolically heterogeneous. Can bioactive lipid cargo differentiate LDL subclasses, and thus potential atherogenicity? What is the effect of statin treatment? Obese hypertriglyceridemic hypercholesterolemic males [n = 12; lipoprotein (a) <10 mg/dl] received pitavastatin calcium (4 mg/day) for 180 days in a single-phase unblinded study. The lipidomic profiles (23 lipid classes) of five LDL subclasses fractionated from baseline and post-statin plasmas were determined by LC-MS. At baseline and on statin treatment, very small dense LDL (LDL5) was preferentially enriched (...
Source: The Journal of Lipid Research - May 31, 2020 Category: Lipidology Authors: Chapman, M. J., Orsoni, A., Tan, R., Mellett, N. A., Nguyen, A., Robillard, P., Giral, P., Therond, P., Meikle, P. J. Tags: Patient-Oriented and Epidemiological Research Source Type: research
Characterization of the small molecule ARC39, a direct and specific inhibitor of acid sphingomyelinase in vitro [Research Articles]
In conclusion, our results indicate that ARC39 potently and selectively inhibits ASM in vitro and highlight the need for developing compounds that can reach tissue concentrations sufficient for ASM inhibition in vivo. (Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - May 31, 2020 Category: Lipidology Authors: Naser, E., Kadow, S., Schumacher, F., Mohamed, Z. H., Kappe, C., Hessler, G., Pollmeier, B., Kleuser, B., Arenz, C., Becker, K. A., Gulbins, E., Carpinteiro, A. Tags: Research Articles Source Type: research
Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS/MS [Research Articles]
Ceramides are the predominant lipids in the stratum corneum (SC) and are crucial components for normal skin barrier function. Although the composition of various ceramide classes in the human SC has been reported, that in mice is still unknown, despite mice being widely used as animal models of skin barrier function. Here, we performed LC/MS/MS analyses using recently available ceramide class standards to measure 25 classes of free ceramides and 5 classes of protein-bound ceramides from human and mouse SC. Phytosphingosine- and 6-hydroxy sphingosine-type ceramides, which both contain an additional hydroxyl group, were abun...
Source: The Journal of Lipid Research - May 31, 2020 Category: Lipidology Authors: Kawana, M., Miyamoto, M., Ohno, Y., Kihara, A. Tags: Research Articles Source Type: research
Metabolic phospholipid labeling of intact bacteria enables a fluorescence assay that detects compromised outer membranes [Research Articles]
Gram-negative bacteria possess an asymmetric outer membrane (OM) composed primarily of lipopolysaccharides (LPSs) on the outer leaflet and phospholipids (PLs) on the inner leaflet. The loss of this asymmetry due to mutations in the LPS biosynthesis or transport pathways causes the externalization of PLs to the outer leaflet of the OM and leads to OM permeability defects. Here, we used metabolic labeling to detect a compromised OM in intact bacteria. Phosphatidylcholine synthase expression in Escherichia coli allowed for the incorporation of exogenous propargylcholine into phosphatidyl(propargyl)choline and exogenous 1-azid...
Source: The Journal of Lipid Research - May 31, 2020 Category: Lipidology Authors: Nilsson, I., Lee, S. Y., Sawyer, W. S., Baxter Rath, C. M., Lapointe, G., Six, D. A. Tags: Research Articles Source Type: research
Skin barrier lipid enzyme activity in Netherton patients is associated with protease activity and ceramide abnormalities [Research Articles]
We examined two key enzymes involved in epidermal ceramide biosynthesis, β-glucocerebrosidase (GBA) and acid-sphingomyelinase (ASM). We compared in situ expression levels and activities of GBA and ASM between NTS patients and controls and correlated the expression and activities with i) SC ceramide profiles, ii) in situ serine protease activity, and iii) clinical presentation of patients. Using activity-based probe labeling, we visualized and localized active epidermal GBA, and a newly developed in situ zymography method enabled us to visualize and localize active ASM. Reduction in active GBA in NTS patients coincided...
Source: The Journal of Lipid Research - May 31, 2020 Category: Lipidology Authors: van Smeden, J., Al-Khakany, H., Wang, Y., Visscher, D., Stephens, N., Absalah, S., Overkleeft, H. S., Aerts, J. M. F. G., Hovnanian, A., Bouwstra, J. A. Tags: Research Articles Source Type: research
Roles of endogenous ether lipids and associated PUFAs in the regulation of ion channels and their relevance for disease [Research Articles]
Ether lipids (ELs) are lipids characterized by the presence of either an ether linkage (alkyl lipids) or a vinyl ether linkage [i.e., plasmalogens (Pls)] at the sn1 position of the glycerol backbone, and they are enriched in PUFAs at the sn2 position. In this review, we highlight that ELs have various biological functions, act as a reservoir for second messengers (such as PUFAs) and have roles in many diseases. Some of the biological effects of ELs may be associated with their ability to regulate ion channels that control excitation-contraction/secretion/mobility coupling and therefore cell physiology. These channels are e...
Source: The Journal of Lipid Research - May 31, 2020 Category: Lipidology Authors: Fontaine, D., Figiel, S., Felix, R., Kouba, S., Fromont, G., Maheo, K., Potier-Cartereau, M., Chantome, A., Vandier, C. Tags: Research Articles Source Type: research
Dietary plant stanol ester supplementation reduces peripheral symptoms in a mouse model of Niemann-Pick type C1 disease [Research Articles]
Niemann-Pick type C (NPC)1 disease is a rare genetic condition in which the function of the lysosomal cholesterol transporter NPC1 protein is impaired. Consequently, sphingolipids and cholesterol accumulate in lysosomes of all tissues, triggering a cascade of pathological events that culminate in severe systemic and neurological symptoms. Lysosomal cholesterol accumulation is also a key factor in the development of atherosclerosis and NASH. In these two metabolic diseases, the administration of plant stanol esters has been shown to ameliorate cellular cholesterol accumulation and inflammation. Given the overlap of patholog...
Source: The Journal of Lipid Research - May 31, 2020 Category: Lipidology Authors: Magro dos Reis, I., Houben, T., Oligschläger, Y., Bücken, L., Steinbusch, H., Cassiman, D., Lütjohann, D., Westerterp, M., Prickaerts, J., Plat, J., Shiri-Sverdlov, R. Tags: Research Articles Source Type: research
Circulating oxidized LDL, increased in patients with acute myocardial infarction, is accompanied by heavily modified HDL [Research Articles]
This study aimed to reveal structural features of oxLDL present in human circulation related to atherosclerosis. When LDL was fractionated on an anion-exchange column, in vivo-oxLDL, detected by the anti-oxidized PC (oxPC) mAb, was recovered in flow-through and electronegative LDL [LDL(–)] fractions. The amount of the electronegative in vivo-oxLDL, namely oxLDL in the LDL(–) fraction, present in patients with acute MI was 3-fold higher than that observed in healthy subjects. Surprisingly, the LDL(–) fraction contained apoA1 in addition to apoB, and HDL-sized particles were observed with transmission elect...
Source: The Journal of Lipid Research - May 31, 2020 Category: Lipidology Authors: Sawada, N., Obama, T., Koba, S., Takaki, T., Iwamoto, S., Aiuchi, T., Kato, R., Kikuchi, M., Hamazaki, Y., Itabe, H. Tags: Research Articles Source Type: research
