Introduction to the Thematic Review Series: Adipose Biology [Thematic Reviews]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - September 30, 2019 Category: Lipidology Authors: Gupta, R. K., Attie, A. D. Tags: Thematic Reviews Source Type: research
A wolf in sheeps clothing: unmasking the lanosterol-induced degradation of HMG-CoA reductase [Commentary]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - September 30, 2019 Category: Lipidology Authors: Coates, H. W., Brown, A. J. Tags: Commentary Source Type: research
Withdrawal: Lipase maturation factor 1 is required for endothelial lipase activity [Withdrawals/Retractions]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - August 31, 2019 Category: Lipidology Authors: Ben-Zeev, O., Hosseini, M., Lai, C.-M., Ehrhardt, N., Wong, H., Cefalu, A. B., Noto, D., Averna, M. R., Doolittle, M. H., Peterfy, M. Tags: Withdrawals/Retractions Source Type: research
Erratum: Comprehensive shotgun lipidomics of human meibomian gland secretions using MS/MSall with successive switching between acquisition polarity modes [Errata]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - August 31, 2019 Category: Lipidology Authors: Chen, J., Nichols, K. K. Tags: Errata Source Type: research
Rare DEGS1 variant significantly alters de novo ceramide synthesis pathway [Patient-Oriented and Epidemiological Research]
The de novo ceramide synthesis pathway is essential to human biology and health, but genetic influences remain unexplored. The core function of this pathway is the generation of biologically active ceramide from its precursor, dihydroceramide. Dihydroceramides have diverse, often protective, biological roles; conversely, increased ceramide levels are biomarkers of complex disease. To explore the genetics of the ceramide synthesis pathway, we searched for deleterious nonsynonymous variants in the genomes of 1,020 Mexican Americans from extended pedigrees. We identified a Hispanic ancestry-specific rare functional variant, L...
Source: The Journal of Lipid Research - August 31, 2019 Category: Lipidology Authors: Blackburn, N. B., Michael, L. F., Meikle, P. J., Peralta, J. M., Mosior, M., McAhren, S., Bui, H. H., Bellinger, M. A., Giles, C., Kumar, S., Leandro, A. C., Almeida, M., Weir, J. M., Mahaney, M. C., Dyer, T. D., Almasy, L., VandeBerg, J. L., Williams-Bla Tags: Patient-Oriented and Epidemiological Research Source Type: research
New evidence from plasma ceramides links apoE polymorphism to greater risk of coronary artery disease in Finnish adults [Patient-Oriented and Epidemiological Research]
In conclusion, new evidence from plasma ceramides links apoE polymorphism with an increased risk of CAD and extends our understanding of the role of apoE in health and disease. (Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - August 31, 2019 Category: Lipidology Authors: Karjalainen, J.-P., Mononen, N., Hutri-Kähönen, N., Lehtimäki, M., Hilvo, M., Kauhanen, D., Juonala, M., Viikari, J., Kähönen, M., Raitakari, O., Laaksonen, R., Lehtimäki, T. Tags: Patient-Oriented and Epidemiological Research Source Type: research
Comparative quantitative systems pharmacology modeling of anti-PCSK9 therapeutic modalities in hypercholesterolemia [Patient-Oriented and Epidemiological Research]
The objective of this research is to set the stage for the quantitative benchmarking of two anti-PCSK9 pharmacological modality classes, monoclonal antibodies (mAbs) and small interfering RNA (siRNA). To this end, we developed an integrative mathematical model of lipoprotein homeostasis describing the dynamic interplay between PCSK9, LDL-cholesterol (LDL-C), VLDL-cholesterol, HDL-cholesterol (HDL-C), apoB, lipoprotein a [Lp(a)], and triglycerides (TGs). We demonstrate that LDL-C decreased proportionally to PCSK9 reduction for both mAb and siRNA modalities. At marketed doses, however, treatment with mAbs resulted in an addi...
Source: The Journal of Lipid Research - August 31, 2019 Category: Lipidology Authors: Sokolov, V., Helmlinger, G., Nilsson, C., Zhudenkov, K., Skrtic, S., Hamren, B., Peskov, K., Hurt-Camejo, E., Jansson-Löfmark, R. Tags: Patient-Oriented and Epidemiological Research Source Type: research
Heritability of apolipoprotein (a) traits in two-generational African-American and Caucasian families [Patient-Oriented and Epidemiological Research]
In conclusion, Lp(a) level and traits associated with the smaller LPA alleles were strongly determined by genetics, although with a varying ethnic influence. Ethnic differences in heritability of the larger LPA allele warrant further investigations. (Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - August 31, 2019 Category: Lipidology Authors: Enkhmaa, B., Anuurad, E., Zhang, W., Kim, K., Berglund, L. Tags: Patient-Oriented and Epidemiological Research Source Type: research
Chemotherapy selection pressure alters sphingolipid composition and mitochondrial bioenergetics in resistant HL-60 cells [Research Articles]
The combination of daunorubicin (dnr) and cytarabine (Ara-C) is a cornerstone of treatment for acute myelogenous leukemia (AML); resistance to these drugs is a major cause of treatment failure. Ceramide, a sphingolipid (SL), plays a critical role in cancer cell apoptosis in response to chemotherapy. Here, we investigated the effects of chemotherapy selection pressure with Ara-C and dnr on SL composition and enzyme activity in the AML cell line HL-60. Resistant cells, those selected for growth in Ara-C- and dnr-containing medium (HL-60/Ara-C and HL-60/dnr, respectively), demonstrated upregulated expression and activity of g...
Source: The Journal of Lipid Research - August 31, 2019 Category: Lipidology Authors: Kao, L.-P., Morad, S. A. F., Davis, T. S., MacDougall, M. R., Kassai, M., Abdelmageed, N., Fox, T. E., Kester, M., Loughran, T. P., Abad, J. L., Fabrias, G., Tan, S.-F., Feith, D. J., Claxton, D. F., Spiegel, S., Fisher-Wellman, K. H., Cabot, M. C. Tags: Research Articles Source Type: research
Lysophosphatidylcholine-induced mitochondrial fission contributes to collagen production in human cardiac fibroblasts [Research Articles]
Lysophosphatidylcholine (LPC) may accumulate in the heart to cause fibrotic events, which is mediated through fibroblast activation and collagen accumulation. Here, we evaluated the mechanisms underlying LPC-mediated collagen induction via mitochondrial events in human cardiac fibroblasts (HCFs), coupling application of the pharmacologic cyclooxygenase-2 (COX-2) inhibitor, celecoxib, and genetic mutations in FOXO1 on the fibrosis pathway. In HCFs, LPC caused prostaglandin E2 (PGE2)/PGE2 receptor 4 (EP4)-dependent collagen induction via activation of transcriptional activity of forkhead box protein O1 (FoxO1) on COX-2 gene ...
Source: The Journal of Lipid Research - August 31, 2019 Category: Lipidology Authors: Tseng, H.-C., Lin, C.-C., Hsiao, L.-D., Yang, C.-M. Tags: Research Articles Source Type: research
Efficient reabsorption of transintestinally excreted cholesterol is a strong determinant for cholesterol disposal in mice [Research Articles]
Transintestinal cholesterol excretion (TICE) is a major route for eliminating cholesterol from the body and a potential therapeutic target for hypercholesterolemia. The underlying mechanism, however, is largely unclear, and its contribution to cholesterol disposal from the body is obscured by the counteracting process of intestinal cholesterol reabsorption. To determine the quantity of TICE independent from its reabsorption, we studied two models of decreased intestinal cholesterol absorption. Cholesterol absorption was inhibited either by ezetimibe or, indirectly, by the genetic inactivation of the intestinal apical sodiu...
Source: The Journal of Lipid Research - August 31, 2019 Category: Lipidology Authors: van de Peppel, I. P., Bertolini, A., van Dijk, T. H., Groen, A. K., Jonker, J. W., Verkade, H. J. Tags: Research Articles Source Type: research
FXR overexpression alters adipose tissue architecture in mice and limits its storage capacity leading to metabolic derangements [Research Articles]
The bile acid-activated nuclear receptor, FXR (NR1H4), has been implicated in the control of lipid and energy metabolism, but its role in fat tissue, where it is moderately expressed, is not understood. In view of the recent development of FXR-targeting therapeutics for treatment of human metabolic diseases, understanding the tissue-specific actions of FXR is essential. Transgenic mice expressing human FXR in adipose tissue (aP2-hFXR mice) at three to five times higher levels than endogenous Fxr, i.e., much lower than its expression in liver and intestine, have markedly enlarged adipocytes and show extensive extracellular ...
Source: The Journal of Lipid Research - August 31, 2019 Category: Lipidology Authors: van Zutphen, T., Stroeve, J. H. M., Yang, J., Bloks, V. W., Jurdzinski, A., Roelofsen, H., Huijkman, N. C. A., van Dijk, T. H., Vonk, R. J., van Deursen, J., Staels, B., Groen, A. K., Kuipers, F. Tags: Research Articles Source Type: research
11{beta}-Hydroxysteroid dehydrogenases control access of 7{beta},27-dihydroxycholesterol to retinoid-related orphan receptor {gamma} [Research Articles]
We examined the role of 11β-HSDs in the enzymatic control of the intracellular availability of 7β,27-dihydroxycholesterol (7β27OHC), a retinoid-related orphan receptor (ROR) ligand. We used microsomal preparations of cells expressing recombinant 11β-HSD1 and 11β-HSD2 to assess whether 7β27OHC and 7-keto,27-hydroxycholesterol (7k27OHC) are substrates of these enzymes. Binding of 7β27OHC and 7k27OHC to 11β-HSDs was studied by molecular modeling. To our knowledge, the stereospecific oxoreduction of 7k27OHC to 7β27OHC by human 11β-HSD1 and the reverse oxidation reaction of 7&be...
Source: The Journal of Lipid Research - August 31, 2019 Category: Lipidology Authors: Beck, K. R., Inderbinen, S. G., Kanagaratnam, S., Kratschmar, D. V., Jetten, A. M., Yamaguchi, H., Odermatt, A. Tags: Research Articles Source Type: research
1H NMR spectroscopy quantifies visibility of lipoproteins, subclasses, and lipids at varied temperatures and pressures [Research Articles]
NMR-based quantification of human lipoprotein (sub)classes is a powerful high-throughput method for medical diagnostics. We evaluated select proton NMR signals of serum lipoproteins for elucidating the physicochemical features and the absolute NMR visibility of their lipids. We separated human lipoproteins of different subclasses by ultracentrifugation and analyzed them by 1H NMR spectroscopy at different temperatures (283–323 K) and pressures (0.1–200 MPa). In parallel, we determined the total lipid content by extraction with chloroform/methanol. The visibility of different lipids in the 1H NMR spectra strongl...
Source: The Journal of Lipid Research - August 31, 2019 Category: Lipidology Authors: Baumstark, D., Kremer, W., Boettcher, A., Schreier, C., Sander, P., Schmitz, G., Kirchhoefer, R., Huber, F., Kalbitzer, H. R. Tags: Research Articles Source Type: research
Intestinal basolateral lipid substrate transport is linked to chylomicron secretion and is regulated by apoC-III [Research Articles]
Chylomicron metabolism is critical for determining plasma levels of triacylglycerols (TAGs) and cholesterol, both of which are risk factors for CVD. The rates of chylomicron secretion and remnant clearance are controlled by intracellular and extracellular factors, including apoC-III. We have previously shown that human apoC-III overexpression in mice (apoC-IIITg mice) decreases the rate of chylomicron secretion into lymph, as well as the TAG composition in chylomicrons. We now find that this decrease in chylomicron secretion is not due to the intracellular effects of apoC-III, but instead that primary murine enteroids are ...
Source: The Journal of Lipid Research - August 31, 2019 Category: Lipidology Authors: Li, D., Rodia, C. N., Johnson, Z. K., Bae, M., Muter, A., Heussinger, A. E., Tambini, N., Longo, A. M., Dong, H., Lee, J.-Y., Kohan, A. B. Tags: Research Articles Source Type: research
