Angiotensinogen in hepatocytes contributes to Western diet-induced liver steatosis [Research Articles]
Nonalcoholic fatty liver disease (NAFLD) is considered as a liver manifestation of metabolic disorders. Previous studies indicate that the renin-angiotensin system (RAS) plays a complex role in NAFLD. As the only precursor of the RAS, decreased angiotensinogen (AGT) profoundly impacts RAS bioactivity. Here, we investigated the role of hepatocyte-derived AGT in liver steatosis. AGT floxed mice (hepAGT+/+) and hepatocyte-specific AGT-deficient mice (hepAGT–/–) were fed a Western diet and a normal laboratory diet for 12 weeks, respectively. Compared with hepAGT+/+ mice, Western diet-fed hepAGT–/– mice ...
Source: The Journal of Lipid Research - December 1, 2019 Category: Lipidology Authors: Tao, X.-R., 陶;昕;然;, , Rong, J.-B., 戎;佳;炳;, , Lu, H. S., 吕;红;, , Daugherty, A., Shi, P., 史;鹏;, , Ke, C.-L., 柯;昌;乐;, , Zhang, Z.-C., 张;召;才;, Tags: Research Articles Source Type: research
In Memoriam: Lawrence (Larry) L. Rudel (1941-2019) [Tribute]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - December 1, 2019 Category: Lipidology Authors: Parks, J. S., Sawyer, J. K., Shelness, G. S., Brown, J. M. Tags: Tribute Source Type: research
Erratum: A monoclonal antibody to assess oxidized cholesteryl esters associated with apoAI and apoB-100 lipoproteins in human plasma [Errata]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - October 31, 2019 Category: Lipidology Authors: Gonen, A., Choi, S.-H., Miu, P., Agatisa-Boyle, C., Acks, D., Taylor, A. M., McNamara, C. A., Tsimikas, S., Witztum, J. L., Miller, Y. I. Tags: Errata Source Type: research
Analytical separations for lipids in complex, nonpolar lipidomes using differential mobility spectrometry [Methods]
Secretions from meibomian glands located within the eyelid (commonly known as meibum) are rich in nonpolar lipid classes incorporating very-long (22–30 carbons) and ultra-long (>30 carbons) acyl chains. The complex nature of the meibum lipidome and its preponderance of neutral, nonpolar lipid classes presents an analytical challenge, with typically poor chromatographic resolution, even between different lipid classes. To address this challenge, we have deployed differential mobility spectrometry (DMS)-MS to interrogate the human meibum lipidome and demonstrate near-baseline resolution of the two major nonpolar cla...
Source: The Journal of Lipid Research - October 31, 2019 Category: Lipidology Authors: Hancock, S. E., Poad, B. L. J., Willcox, M. D. P., Blanksby, S. J., Mitchell, T. W. Tags: Methods Source Type: research
A new method for measuring cholesterol efflux capacity uses stable isotope-labeled, not radioactive-labeled, cholesterol [Methods]
The incidence of cardiovascular events correlates inversely with cholesterol efflux capacity (CEC) more than with HDL-cholesterol level. The measurement of CEC is used to qualify cardiovascular disease risk and is conventionally performed with radioisotope (RI)-labeled cholesterol. Here, we established a CEC measurement technique using stable isotope-labeled cholesterol as an alternative, and we compared the new method with RI and fluorescence (boron dipyrromethene difluoride-cholesterol) methods in cells and in patient serum. We incubated J774 cells labeled with [d7]cholesterol ([d7]C) with patient serum depleted of apoB,...
Source: The Journal of Lipid Research - October 31, 2019 Category: Lipidology Authors: Shimizu, T., Miyazaki, O., Iwamoto, T., Usui, T., Sato, R., Hiraishi, C., Yoshida, H. Tags: Methods Source Type: research
Partial LPL deletions: rare copy-number variants contributing towards severe hypertriglyceridemia [Patient-Oriented and Epidemiological Research]
Severe hypertriglyceridemia (HTG) is a relatively common form of dyslipidemia with a complex pathophysiology and serious health complications. HTG can develop in the presence of rare genetic factors disrupting genes involved in the triglyceride (TG) metabolic pathway, including large-scale copy-number variants (CNVs). Improvements in next-generation sequencing technologies and bioinformatic analyses have better allowed assessment of CNVs as possible causes of or contributors to severe HTG. We screened targeted sequencing data of 632 patients with severe HTG and identified partial deletions of the LPL gene, encoding the cen...
Source: The Journal of Lipid Research - October 31, 2019 Category: Lipidology Authors: Dron, J. S., Wang, J., McIntyre, A. D., Cao, H., Robinson, J. F., Duell, P. B., Manjoo, P., Feng, J., Movsesyan, I., Malloy, M. J., Pullinger, C. R., Kane, J. P., Hegele, R. A. Tags: Patient-Oriented and Epidemiological Research Source Type: research
PCSK9 loss-of-function variants and Lp(a) phenotypes among black US adults [Patient-Oriented and Epidemiological Research]
The pharmacologic inhibition of proprotein convertase subtilisin-kexin type 9 (PCSK9) lowers lipoprotein (a) [Lp(a)] concentrations. However, the impact of genetic PCSK9 loss-of-function variants (LOFVs) on Lp(a) is uncertain. We determined the association of PCSK9 LOFVs with Lp(a) measures among black adults. Genotyping for PCSK9 LOFVs was conducted in 10,196 black Reasons for Geographic and Racial Differences in Stroke study participants. Among 241 participants with and 723 randomly selected participants without PCSK9 LOFVs, Lp(a) concentations, apo(a) kringle IV (KIV) repeats (a proxy for isoform size), and oxidized pho...
Source: The Journal of Lipid Research - October 31, 2019 Category: Lipidology Authors: Mefford, M. T., Marcovina, S. M., Bittner, V., Cushman, M., Brown, T. M., Farkouh, M. E., Tsimikas, S., Monda, K. L., Lopez, J. A. G., Muntner, P., Rosenson, R. S. Tags: Patient-Oriented and Epidemiological Research Source Type: research
Four nights of sleep restriction suppress the postprandial lipemic response and decrease satiety [Patient-Oriented and Epidemiological Research]
Chronic sleep restriction, or inadequate sleep, is associated with increased risk of cardiometabolic disease. Laboratory studies demonstrate that sleep restriction causes impaired whole-body insulin sensitivity and glucose disposal. Evidence suggests that inadequate sleep also impairs adipose tissue insulin sensitivity and the NEFA rebound during intravenous glucose tolerance tests, yet no studies have examined the effects of sleep restriction on high-fat meal lipemia. We assessed the effect of 5 h time in bed (TIB) per night for four consecutive nights on postprandial lipemia following a standardized high-fat dinner (HFD)...
Source: The Journal of Lipid Research - October 31, 2019 Category: Lipidology Authors: Ness, K. M., Strayer, S. M., Nahmod, N. G., Schade, M. M., Chang, A.-M., Shearer, G. C., Buxton, O. M. Tags: Patient-Oriented and Epidemiological Research Source Type: research
Metabolism of cholesterol and progesterone is differentially regulated in primary trophoblastic subtypes and might be disturbed in recurrent miscarriages [Patient-Oriented and Epidemiological Research]
During pregnancy, extravillous trophoblasts (EVTs) invade the maternal decidua and remodel the local vasculature to establish blood supply for the growing fetus. Compromised EVT function has been linked to aberrant pregnancy associated with maternal and fetal morbidity and mortality. However, metabolic features of this invasive trophoblast subtype are largely unknown. Using primary human trophoblasts isolated from first trimester placental tissues, we show that cellular cholesterol homeostasis is differentially regulated in EVTs compared with villous cytotrophoblasts. Utilizing RNA-sequencing, gene set-enrichment analysis,...
Source: The Journal of Lipid Research - October 31, 2019 Category: Lipidology Authors: Vondra, S., Kunihs, V., Eberhart, T., Eigner, K., Bauer, R., Haslinger, P., Haider, S., Windsperger, K., Klambauer, G., Schütz, B., Mikula, M., Zhu, X., Urban, A. E., Hannibal, R. L., Baker, J., Knöfler, M., Stangl, H., Pollheimer, J., Ro& Tags: Patient-Oriented and Epidemiological Research Source Type: research
Identification of ApoA4 as a sphingosine 1-phosphate chaperone in ApoM- and albumin-deficient mice [Research Articles]
In this study, we report the identification of ApoA4 as a novel S1P binding protein. Recombinant ApoA4 bound to S1P, activated multiple S1P receptors, and promoted vascular endothelial barrier function, all reflective of its function as a S1P chaperone in the absence of ApoM and albumin. We suggest that multiple S1P chaperones evolved to support complex and essential extracellular signaling functions of this lysolipid mediator in a redundant manner. (Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - October 31, 2019 Category: Lipidology Authors: Obinata, H., Kuo, A., Wada, Y., Swendeman, S., Liu, C. H., Blaho, V. A., Nagumo, R., Satoh, K., Izumi, T., Hla, T. Tags: Research Articles Source Type: research
Plasma oxyphytosterol concentrations are not associated with CVD status in Framingham Offspring Study participants [Research Articles]
In conclusion, circulating plasma oxyphytosterols are not associated with CVD risk in the Framingham Offspring Study. (Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - October 31, 2019 Category: Lipidology Authors: Baumgartner, S., Ras, R. T., Trautwein, E. A., Konings, M. C. J. M., Mensink, R. P., Plat, J. Tags: Research Articles Source Type: research
Bacterial immunogenic {alpha}-galactosylceramide identified in the murine large intestine: dependency on diet and inflammation [Research Articles]
The glycosphingolipid, α-galactosylceramide (αGalCer), when presented by CD1d on antigen-presenting cells, efficiently activates invariant natural killer T (iNKT) cells. Thereby, it modulates immune responses against tumors, microbial and viral infections, and autoimmune diseases. Recently, the production of αGalCer by Bacteroidetes from the human gut microbiome was elucidated. Using hydrophilic interaction chromatography coupled to MS2, we screened murine intestinal tracts to identify and quantify αGalCers, and we investigated the αGalCer response to different dietary and physiologic conditio...
Source: The Journal of Lipid Research - October 31, 2019 Category: Lipidology Authors: von Gerichten, J., Lamprecht, D., Opalka, L., Soulard, D., Marsching, C., Pilz, R., Sencio, V., Herzer, S., Galy, B., Nordström, V., Hopf, C., Gröne, H.-J., Trottein, F., Sandhoff, R. Tags: Research Articles Source Type: research
Lipid species affect morphology of endoplasmic reticulum: a sea urchin oocyte model of reversible manipulation [Research Articles]
The ER is a large multifunctional organelle of eukaryotic cells. Malfunction of the ER in various disease states, such as atherosclerosis, diabetes, cancer, Alzheimer’s and Parkinson’s and amyotrophic lateral sclerosis, often correlates with alterations in its morphology. The ER exhibits regionally variable membrane morphology that includes, at the extremes, large relatively flat surfaces and interconnected tubular structures highly curved in cross-section. ER morphology is controlled by shaping proteins that associate with membrane lipids. To investigate the role of these lipids, we developed a sea urchin oocy...
Source: The Journal of Lipid Research - October 31, 2019 Category: Lipidology Authors: Ulloa, G., Hamati, F., Dick, A., Fitzgerald, J., Mantell, J., Verkade, P., Collinson, L., Arkill, K., Larijani, B., Poccia, D. Tags: Research Articles Source Type: research
ApoF knockdown increases cholesteryl ester transfer to LDL and impairs cholesterol clearance in fat-fed hamsters [Research Articles]
Cholesteryl ester transfer protein (CETP) regulates intravascular lipoprotein metabolism. In vitro studies indicate that ApoF alters CETP function by inhibiting its activity with LDL. To explore in vivo the complexities driving ApoF’s effects on CETP, we developed a siRNA-based hamster model of ApoF knockdown. In both male and female hamsters on chow- or fat-fed diets, we measured lipoprotein levels and composition, determined CETP-mediated transfer of cholesteryl esters (CEs) between lipoproteins, and quantified reverse cholesterol transport (RCT). We found that apoF knockdown in chow-fed hamsters had no effect on l...
Source: The Journal of Lipid Research - October 31, 2019 Category: Lipidology Authors: Morton, R. E., Liu, Y., Izem, L. Tags: Research Articles Source Type: research
Role of {beta}-glucosidase 2 in aberrant glycosphingolipid metabolism: model of glucocerebrosidase deficiency in zebrafish [Research Articles]
β-glucosidases [GBA1 (glucocerebrosidase) and GBA2] are ubiquitous essential enzymes. Lysosomal GBA1 and cytosol-facing GBA2 degrade glucosylceramide (GlcCer); GBA1 deficiency causes Gaucher disease, a lysosomal storage disorder characterized by lysosomal accumulation of GlcCer, which is partly converted to glucosylsphingosine (GlcSph). GBA1 and GBA2 also may transfer glucose from GlcCer to cholesterol, yielding glucosylated cholesterol (GlcChol). Here, we aimed to clarify the role of zebrafish Gba2 in glycosphingolipid metabolism during Gba1 deficiency in zebrafish (Danio rerio), which are able to survive total Gba1 ...
Source: The Journal of Lipid Research - October 31, 2019 Category: Lipidology Authors: Lelieveld, L. T., Mirzaian, M., Kuo, C.-L., Artola, M., Ferraz, M. J., Peter, R. E. A., Akiyama, H., Greimel, P., van den Berg, R. J. B. H. N., Overkleeft, H. S., Boot, R. G., Meijer, A. H., Aerts, J. M. F. G. Tags: Research Articles Source Type: research
