Effects of omega-O-acylceramide structures and concentrations in healthy and diseased skin barrier lipid membrane models [Research Articles]
Ceramides (Cers) with ultralong (~32-carbon) chains and -esterified linoleic acid, composing a subclass called omega-O-acylceramides (acylCers), are indispensable components of the skin barrier. Normal barriers typically contain acylCer concentrations of ~10 mol%; diminished concentrations, along with altered or missing long periodicity lamellar phase (LPP), and increased permeability accompany an array of skin disorders, including atopic dermatitis, psoriasis, and ichthyoses. We developed model membranes to investigate the effects of the acylCer structure and concentration on skin lipid organization and permeability. The ...
Source: The Journal of Lipid Research - January 31, 2020 Category: Lipidology Authors: Opalka, L., Kovacik, A., Pullmannova, P., Maixner, J., Vavrova, K. Tags: Research Articles Source Type: research

Endocytosis of very low-density lipoproteins: an unexpected mechanism for lipid acquisition by breast cancer cells [Research Articles]
We previously described the expression of CD36 and LPL by breast cancer (BC) cells and tissues and the growth-promoting effect of VLDL observed only in the presence of LPL. We now report a model in which LPL is bound to a heparan sulfate proteoglycan motif on the BC cell surface and acts in concert with the VLDL receptor to internalize VLDLs via receptor-mediated endocytosis. We also demonstrate that gene-expression programs for lipid synthesis versus uptake respond robustly to triglyceride-rich lipoprotein availability. The literature emphasizes de novo FA synthesis and exogenous free FA uptake using CD36 as paramount mec...
Source: The Journal of Lipid Research - January 31, 2020 Category: Lipidology Authors: Lupien, L. E., Bloch, K., Dehairs, J., Traphagen, N. A., Feng, W. W., Davis, W. L., Dennis, T., Swinnen, J. V., Wells, W. A., Smits, N. C., Kuemmerle, N. B., Miller, T. W., Kinlaw, W. B. Tags: Research Articles Source Type: research

A nematode sterol C4{alpha}-methyltransferase catalyzes a new methylation reaction responsible for sterol diversity [Research Articles]
Primitive sterol evolution plays an important role in fossil record interpretation and offers potential therapeutic avenues for human disease resulting from nematode infections. Recognizing that C4-methyl stenol products [8(14)-lophenol] can be synthesized in bacteria while C4-methyl stanol products (dinosterol) can be synthesized in dinoflagellates and preserved as sterane biomarkers in ancient sedimentary rock is key to eukaryotic sterol evolution. In this regard, nematodes have been proposed to convert dietary cholesterol to 8(14)-lophenol by a secondary metabolism pathway that could involve sterol C4 methylation analog...
Source: The Journal of Lipid Research - January 31, 2020 Category: Lipidology Authors: Zhou, W., Fisher, P. M., Vanderloop, B. H., Shen, Y., Shi, H., Maldonado, A. J., Leaver, D. J., Nes, W. D. Tags: Research Articles Source Type: research

Lipid droplet-associated kinase STK25 regulates peroxisomal activity and metabolic stress response in steatotic liver [Research Articles]
Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are emerging as leading causes of liver disease worldwide and have been recognized as one of the major unmet medical needs of the 21st century. Our recent translational studies in mouse models, human cell lines, and well-characterized patient cohorts have identified serine/threonine kinase (STK)25 as a protein that coats intrahepatocellular lipid droplets (LDs) and critically regulates liver lipid homeostasis and progression of NAFLD/NASH. Here, we studied the mechanism-of-action of STK25 in steatotic liver by relative quantification of the he...
Source: The Journal of Lipid Research - January 31, 2020 Category: Lipidology Authors: Nerstedt, A., Kurhe, Y., Cansby, E., Caputo, M., Gao, L., Vorontsov, E., Stahlman, M., Nunez-Duran, E., Boren, J., Marschall, H.-U., Mashek, D. G., Saunders, D. N., Sihlbom, C., Hoy, A. J., Mahlapuu, M. Tags: Research Articles Source Type: research

Quantification of bile acids: a mass spectrometry platform for studying gut microbe connection to metabolic diseases [Research Articles]
Bile acids (BAs) serve multiple biological functions, ranging from the absorption of lipids and fat-soluble vitamins to serving as signaling molecules through the direct activation of dedicated cellular receptors. Synthesized by both host and microbial pathways, BAs are increasingly understood as participating in the regulation of numerous pathways relevant to metabolic diseases, including lipid and glucose metabolism, energy expenditure, and inflammation. Quantitative analyses of BAs in biological matrices can be problematic due to their unusual and diverse physicochemical properties, making optimization of a method that ...
Source: The Journal of Lipid Research - January 31, 2020 Category: Lipidology Authors: Choucair, I., Nemet, I., Li, L., Cole, M. A., Skye, S. M., Kirsop, J. D., Fischbach, M. A., Gogonea, V., Brown, J. M., Tang, W. H. W., Hazen, S. L. Tags: Research Articles Source Type: research

Macrophage polarization is linked to Ca2+-independent phospholipase A2{beta}-derived lipids and cross-cell signaling in mice [Research Articles]
Phospholipases A2 (PLA2s) catalyze hydrolysis of the sn-2 substituent from glycerophospholipids to yield a free fatty acid (i.e., arachidonic acid), which can be metabolized to pro- or anti-inflammatory eicosanoids. Macrophages modulate inflammatory responses and are affected by Ca2+-independent phospholipase A2 (PLA2)β (iPLA2β). Here, we assessed the link between iPLA2β-derived lipids (iDLs) and macrophage polarization. Macrophages from WT and KO (iPLA2β–/–) mice were classically M1 pro-inflammatory phenotype activated or alternatively M2 anti-inflammatory phenotype activated, and eicosanoi...
Source: The Journal of Lipid Research - January 31, 2020 Category: Lipidology Authors: Nelson, A. J., Stephenson, D. J., Cardona, C. L., Lei, X., Almutairi, A., White, T. D., Tusing, Y. G., Park, M. A., Barbour, S. E., Chalfant, C. E., Ramanadham, S. Tags: Research Articles Source Type: research

Novel GPR120 agonist TUG891 modulates fat taste perception and preference and activates tongue-brain-gut axis in mice [Research Articles]
GPR120 is implicated as a lipid receptor in the oro-sensory detection of dietary fatty acids. However, the effects of GPR120 activation on dietary fat intake or obesity are not clearly understood. We investigated to determine whether the binding of TUG891, a novel GPR120 agonist, to lingual GPR120 modulates fat preference in mice. We explored the effects of TUG891 on obesity-related hormones and conducted behavioral choice tests on mice to better understand the physiologic relevance of the action of TUG891. In cultured mouse and human taste bud cells (TBCs), TUG891 induced a rapid increase in Ca2+ by acting on GPR120. A lo...
Source: The Journal of Lipid Research - January 31, 2020 Category: Lipidology Authors: Murtaza, B., Hichami, A., Khan, A. S., Shimpukade, B., Ulven, T., Ozdener, M. H., Khan, N. A. Tags: Research Articles Source Type: research

Worming our way toward multiple evolutionary origins of convergent sterol pathways [Commentary]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - January 31, 2020 Category: Lipidology Authors: Darnet, S., Fliesler, S. J., Schaller, H. Tags: Commentary Source Type: research

Withdrawal: Regulatory T cells suppress excessive lipid accumulation in alcoholic liver disease [Withdrawals/Retractions]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - December 31, 2019 Category: Lipidology Authors: Wang, H., Wu, T., Wang, Y., Wan, X., Qi, J., Li, L., Wang, X., Luo, X., Ning, Q. Tags: Withdrawals/Retractions Source Type: research

Turnover of brain DHA in mice is accurately determined by tracer-free natural abundance carbon isotope ratio analysis [Methods]
The brain is highly enriched in the long-chain omega-3 (n-3) PUFA DHA. Due to the limited capacity for local DHA synthesis in the brain, it relies on a continual supply from the circulation to replenish metabolized DHA. Previous studies investigating brain DHA turnover and metabolism have relied on isotope tracers to determine brain fatty acid kinetics; however, this approach is cumbersome and costly. We applied natural abundance carbon isotope ratio analysis via high-precision gas chromatography combustion isotope ratio mass spectrometry, without the use of labeled tracers, to determine the half-life of brain DHA in mice ...
Source: The Journal of Lipid Research - December 31, 2019 Category: Lipidology Authors: Lacombe, R. J. S., Lee, C.-C., Bazinet, R. P. Tags: Methods Source Type: research

Shared reference materials harmonize lipidomics across MS-based detection platforms and laboratories [Methods]
Quantitative MS of human plasma lipids is a promising technology for translation into clinical applications. Current MS-based lipidomic methods rely on either direct infusion (DI) or chromatographic lipid separation methods (including reversed phase and hydrophilic interaction LC). However, the use of lipid markers in laboratory medicine is limited by the lack of reference values, largely because of considerable differences in the concentrations measured by different laboratories worldwide. These inconsistencies can be explained by the use of different sample preparation protocols, method-specific calibration procedures, a...
Source: The Journal of Lipid Research - December 31, 2019 Category: Lipidology Authors: Triebl, A., Burla, B., Selvalatchmanan, J., Oh, J., Tan, S. H., Chan, M. Y., Mellet, N. A., Meikle, P. J., Torta, F., Wenk, M. R. Tags: Methods Source Type: research

Lipidome-wide 13C flux analysis: a novel tool to estimate the turnover of lipids in organisms and cultures [Methods]
Lipid metabolism plays an important role in the regulation of cellular homeostasis. However, because it is difficult to measure the actual rates of synthesis and degradation of individual lipid species, lipid compositions are often used as a surrogate to evaluate lipid metabolism even though they provide only static snapshots of the lipodome. Here, we designed a simple method to determine the turnover rate of phospholipid and acylglycerol species based on the incorporation of 13C6-glucose combined with LC-MS/MS. We labeled adult Drosophila melanogaster with 13C6-glucose that incorporates into the entire lipidome, derived k...
Source: The Journal of Lipid Research - December 31, 2019 Category: Lipidology Authors: Schlame, M., Xu, Y., Erdjument-Bromage, H., Neubert, T. A., Ren, M. Tags: Methods Source Type: research

The interaction between ABCA1 polymorphism and physical activity on the HDL-cholesterol levels in a Japanese population [Patient-Oriented and Epidemiological Research]
Few studies have investigated the interactions between HDL-C-related SNPs identified by genome-wide association (GWA) study and physical activity (PA) on HDL-C. First, we conducted a sex-stratified GWA study in a discovery sample (2,231 men and 2,431 women) and replication sample (2,599 men and 3,109 women) to identify SNPs influencing log-transformed HDL-C in Japanese participants in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. We also replicated previously reported HDL-C-related SNPs in a combined (discovery plus replication) sample (4,830 men and 5,540 women). We then analyzed the int...
Source: The Journal of Lipid Research - December 31, 2019 Category: Lipidology Authors: Nishida, Y., Hachiya, T., Hara, M., Shimanoe, C., Tanaka, K., Sutoh, Y., Shimizu, A., Hishida, A., Tsukamoto, M., Kadomatsu, Y., Oze, I., Koyanagi, Y. N., Kuriyama, N., Koyama, T., Ibusuki, R., Takezaki, T., Ikezaki, H., Furusyo, N., Takashima, N., Kadota Tags: Patient-Oriented and Epidemiological Research Source Type: research

Germ-free mice exhibit profound gut microbiota-dependent alterations of intestinal endocannabinoidome signaling [Research Articles]
The gut microbiota is a unique ecosystem of microorganisms interacting with the host through several biochemical mechanisms. The endocannabinoidome (eCBome), a complex signaling system including the endocannabinoid system, approximately 50 receptors and metabolic enzymes, and more than 20 lipid mediators with important physiopathologic functions, modulates gastrointestinal tract function and may mediate host cell-microbe communications there. Germ-free (GF) mice, which lack an intestinal microbiome and so differ drastically from conventionally raised (CR) mice, offer a unique opportunity to explore the eCBome in a microbe-...
Source: The Journal of Lipid Research - December 31, 2019 Category: Lipidology Authors: Manca, C., Boubertakh, B., Leblanc, N., Deschenes, T., Lacroix, S., Martin, C., Houde, A., Veilleux, A., Flamand, N., Muccioli, G. G., Raymond, F., Cani, P. D., Di Marzo, V., Silvestri, C. Tags: Research Articles Source Type: research

Regulation of bile acid metabolism in mouse models with hydrophobic bile acid composition [Research Articles]
The bile acid (BA) composition in mice is substantially different from that in humans. Chenodeoxycholic acid (CDCA) is an end product in the human liver; however, mouse Cyp2c70 metabolizes CDCA to hydrophilic muricholic acids (MCAs). Moreover, in humans, the gut microbiota converts the primary BAs, cholic acid and CDCA, into deoxycholic acid (DCA) and lithocholic acid (LCA), respectively. In contrast, the mouse Cyp2a12 reverts this action and converts these secondary BAs to primary BAs. Here, we generated Cyp2a12 KO, Cyp2c70 KO, and Cyp2a12/Cyp2c70 double KO (DKO) mice using the CRISPR-Cas9 system to study the regulation o...
Source: The Journal of Lipid Research - December 31, 2019 Category: Lipidology Authors: Honda, A., Miyazaki, T., Iwamoto, J., Hirayama, T., Morishita, Y., Monma, T., Ueda, H., Mizuno, S., Sugiyama, F., Takahashi, S., Ikegami, T. Tags: Research Articles Source Type: research