Probing compartment-specific sphingolipids with targeted bacterial sphingomyelinases and ceramidases [Research Articles]
Sphingolipids contribute to the regulation of cell and tissue homeostasis, and disorders of sphingolipid metabolism lead to diseases such as inflammation, stroke, diabetes, and cancer. Sphingolipid metabolic pathways involve an array of enzymes that reside in specific subcellular organelles, resulting in the formation of many diverse sphingolipids with distinct molecular species based on the diversity of the ceramide (Cer) structure. In order to probe compartment-specific metabolism of sphingolipids in this study, we analyzed the Cer and SM species preferentially produced in the inner plasma membrane (PM), Golgi apparatus,...
Source: The Journal of Lipid Research - October 31, 2019 Category: Lipidology Authors: Sakamoto, W., Canals, D., Salamone, S., Allopenna, J., Clarke, C. J., Snider, J., Obeid, L. M., Hannun, Y. A. Tags: Research Articles Source Type: research
Novel COX-2 products of n-3 polyunsaturated fatty acid-ethanolamine-conjugates identified in RAW264.7 macrophages [Research Articles]
Cyclooxygenase 2 (COX-2) plays a key role in the regulation of inflammation by catalyzing the oxygenation of PUFAs to prostaglandins (PGs) and hydroperoxides. Next to this, COX-2 can metabolize neutral lipids, including endocannabinoid-like esters and amides. We developed an LC-HRMS-based human recombinant (h)COX-2 screening assay to examine its ability to also convert n-3 PUFA-derived N-acylethanolamines. Our assay yields known hCOX-2-derived products from established PUFAs and anandamide. Subsequently, we proved that eicosapentaenoylethanolamide (EPEA), the N-acylethanolamine derivative of EPA, is converted into PGE3-eth...
Source: The Journal of Lipid Research - October 31, 2019 Category: Lipidology Authors: de Bus, I., Zuilhof, H., Witkamp, R., Balvers, M., Albada, B. Tags: Research Articles Source Type: research
Effects of diet and hyperlipidemia on levels and distribution of circulating lysophosphatidic acid [Research Articles]
We examined the effects of experimental hyperlipidemia on the levels and distribution of circulating LPA in mice. The majority of plasma LPA was associated with albumin in plasma from wild-type mice fed normal chow. LDL-associated LPA was increased in plasma from high-fat Western diet-fed mice that are genetically prone to hyperlipidemia (LDL receptor knockout or activated proprotein convertase subtilisin/kexin type 9-overexpressing C57Bl6). Adipose-specific deficiency of the ENPP2 gene encoding the LPA-generating secreted lysophospholipase D, autotaxin (ATX), attenuated these Western diet-dependent increases in LPA. ATX-d...
Source: The Journal of Lipid Research - October 31, 2019 Category: Lipidology Authors: Kraemer, M. P., Mao, G., Hammill, C., Yan, B., Li, Y., Onono, F., Smyth, S. S., Morris, A. J. Tags: Research Articles Source Type: research
Metabolic role of fatty acid binding protein 7 in mediating triple-negative breast cancer cell death via PPAR-{alpha} signaling [Research Articles]
This study provides imperative evidence of metabolic vulnerabilities driven by FABP7 via PPAR-α signaling. (Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - October 31, 2019 Category: Lipidology Authors: Kwong, S. C., Jamil, A. H. A., Rhodes, A., Taib, N. A., Chung, I. Tags: Research Articles Source Type: research
{alpha}-Galactosylceramide: a potent immunomodulator produced by gut microbes [Commentary]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - October 31, 2019 Category: Lipidology Authors: Carr, R. M. Tags: Commentary Source Type: research
DGAT2 partially compensates for lipid-induced ER stress in human DGAT1-deficient intestinal stem cells [Patient-Oriented and Epidemiological Research]
Dietary lipids are taken up as FAs by the intestinal epithelium and converted by diacylglycerol acyltransferase (DGAT) enzymes into triglycerides, which are packaged in chylomicrons or stored in cytoplasmic lipid droplets (LDs). DGAT1-deficient patients suffer from vomiting, diarrhea, and protein losing enteropathy, illustrating the importance of this process to intestinal homeostasis. Previously, we have shown that DGAT1 deficiency causes decreased LD formation and resistance to unsaturated FA lipotoxicity in patient-derived intestinal organoids. However, LD formation was not completely abolished in patient-derived organo...
Source: The Journal of Lipid Research - September 30, 2019 Category: Lipidology Authors: van Rijn, J. M., van Hoesel, M., de Heus, C., van Vugt, A. H. M., Klumperman, J., Nieuwenhuis, E. E. S., Houwen, R. H. J., Middendorp, S. Tags: Patient-Oriented and Epidemiological Research Source Type: research
High FA2H and UGT8 transcript levels predict hydroxylated hexosylceramide accumulation in lung adenocarcinoma [Patient-Oriented and Epidemiological Research]
In this study, we paralleled quantification of sphingolipid species with quantitative (q)PCR analyses of metabolic enzymes in order to identify dysregulated routes of sphingolipid metabolism in different subtypes of lung cancers. Lung samples were submitted to histopathological reexamination in order to confirm cancer type/subtype, which included adenocarcinoma histological subtypes and squamous cell and neuroendocrine carcinomas. Compared with benign lesions and tumor-free parenchyma, all cancers featured decreased sphingosine-1-phosphate and SMs. qPCR analyses evidenced differential mechanisms leading to these alteration...
Source: The Journal of Lipid Research - September 30, 2019 Category: Lipidology Authors: Lemay, A.-M., Courtemanche, O., Couttas, T. A., Jamsari, G., Gagne, A., Bosse, Y., Joubert, P., Don, A. S., Marsolais, D. Tags: Patient-Oriented and Epidemiological Research Source Type: research
Endogenous sterol intermediates of the mevalonate pathway regulate HMGCR degradation and SREBP-2 processing [Research Articles]
Sterol-regulated HMG-CoA reductase (HMGCR) degradation and SREBP-2 cleavage are two major feedback regulatory mechanisms governing cholesterol biosynthesis. Reportedly, lanosterol selectively stimulates HMGCR degradation, and cholesterol is a specific regulator of SREBP-2 cleavage. However, it is unclear whether other endogenously generated sterols regulate these events. Here, we investigated the sterol intermediates from the mevalonate pathway of cholesterol biosynthesis using a CRISPR/Cas9-mediated genetic engineering approach. With a constructed HeLa cell line expressing the mevalonate transporter, we individually delet...
Source: The Journal of Lipid Research - September 30, 2019 Category: Lipidology Authors: Chen, L., Ma, M.-Y., Sun, M., Jiang, L.-Y., Zhao, X.-T., Fang, X.-X., Man Lam, S., Shui, G.-H., Luo, J., Shi, X.-J., Song, B.-L. Tags: Research Articles Source Type: research
SAR1B GTPase is necessary to protect intestinal cells from disorders of lipid homeostasis, oxidative stress, and inflammation [Research Articles]
In conclusion, SAR1B and its paralogue are needed not only for CM trafficking but also for lipid homeostasis, prooxidant/antioxidant balance, and protection against inflammatory processes. (Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - September 30, 2019 Category: Lipidology Authors: Sane, A., Ahmarani, L., Delvin, E., Auclair, N., Spahis, S., Levy, E. Tags: Research Articles Source Type: research
Characterization of ANGPTL4 function in macrophages and adipocytes using Angptl4-knockout and Angptl4-hypomorphic mice [Research Articles]
In conclusion, ANGPTL4 deficiency increases lipid uptake and respiration in macrophages without affecting LPL protein levels. Compared with the absence of ANGPTL4, low levels of N-terminal ANGPTL4 mitigate the development of chylous ascites and an acute-phase response in mice. (Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - September 30, 2019 Category: Lipidology Authors: Oteng, A.-B., Ruppert, P. M. M., Boutens, L., Dijk, W., van Dierendonck, X. A. M. H., Olivecrona, G., Stienstra, R., Kersten, S. Tags: Research Articles Source Type: research
In search of a genetic explanation for LDLc variability in an FH family: common SNPs and a rare mutation in MTTP explain only part of LDL variability in an FH family [Research Articles]
We previously identified a highly consanguineous familial hypercholesterolemia (FH) family demonstrating segregation of the JD Bari mutation in the LDL receptor as well as a putative cholesterol-lowering trait. We aimed to identify genes related to the latter effect. LDL cholesterol (LDLc) values were normalized for FH affectation status, age, and gender. Using genome-wide SNP data, we examined whether known SNPs gleaned from a genome-wide association study could explain the variation observed in LDLc. Four individuals with markedly reduced LDL levels underwent whole exome sequencing. After prioritizing all potential mutat...
Source: The Journal of Lipid Research - September 30, 2019 Category: Lipidology Authors: Winther, M., Shpitzen, S., Yaacov, O., Landau, J., Oren, L., Foroozan-Rosenberg, L., Lev Cohain, N., Schurr, D., Meiner, V., Szalat, A., Carmi, S., Hayden, M. R., Leitersdorf, E., Durst, R. Tags: Research Articles Source Type: research
Muscle and adipose tissue insulin resistance: malady without mechanism? [Thematic Reviews]
Insulin resistance is a major risk factor for numerous diseases, including type 2 diabetes and cardiovascular disease. These disorders have dramatically increased in incidence with modern life, suggesting that excess nutrients and obesity are major causes of "common" insulin resistance. Despite considerable effort, the mechanisms that contribute to common insulin resistance are not resolved. There is universal agreement that extracellular perturbations, such as nutrient excess, hyperinsulinemia, glucocorticoids, or inflammation, trigger intracellular stress in key metabolic target tissues, such as muscle and adipose tissue...
Source: The Journal of Lipid Research - September 30, 2019 Category: Lipidology Authors: Fazakerley, D. J., Krycer, J. R., Kearney, A. L., Hocking, S. L., James, D. E. Tags: Thematic Reviews Source Type: research
Determinants of body fat distribution in humans may provide insight about obesity-related health risks [Thematic Reviews]
Obesity increases the risks of developing cardiovascular and metabolic diseases and degrades quality of life, ultimately increasing the risk of death. However, not all forms of obesity are equally dangerous: some individuals, despite higher percentages of body fat, are at less risk for certain chronic obesity-related complications. Many open questions remain about why this occurs. Data suggest that the physical location of fat and the overall health of fat dramatically influence disease risk; for example, higher concentrations of visceral relative to subcutaneous adipose tissue are associated with greater metabolic risks. ...
Source: The Journal of Lipid Research - September 30, 2019 Category: Lipidology Authors: Frank, A. P., de Souza Santos, R., Palmer, B. F., Clegg, D. J. Tags: Thematic Reviews Source Type: research
Contributions of innate type 2 inflammation to adipose function [Thematic Reviews]
A critical contributor to the health consequences of the obesity epidemic is dysregulated adipose tissue (AT) homeostasis. While white, brown, and beige AT function is altered in obesity-related disease, white AT is marked by progressive inflammation and adipocyte dysfunction and has been the focus of extensive "immunometabolism" research in the past decade. The exact triggering events initiating and sustaining AT inflammation are still under study, but it has been shown that reducing inflammation improves insulin action in AT. Scientific efforts seeking interventions to mitigate obesity-associated AT inflammation continue...
Source: The Journal of Lipid Research - September 30, 2019 Category: Lipidology Authors: Bolus, W. R., Hasty, A. H. Tags: Thematic Reviews Source Type: research
Beyond adiponectin and leptin: adipose tissue-derived mediators of inter-organ communication [Thematic Reviews]
The breakthrough discoveries of leptin and adiponectin more than two decades ago led to a widespread recognition of adipose tissue as an endocrine organ. Many more adipose tissue-secreted signaling mediators (adipokines) have been identified since then, and much has been learned about how adipose tissue communicates with other organs of the body to maintain systemic homeostasis. Beyond proteins, additional factors, such as lipids, metabolites, noncoding RNAs, and extracellular vesicles (EVs), released by adipose tissue participate in this process. Here, we review the diverse signaling mediators and mechanisms adipose tissu...
Source: The Journal of Lipid Research - September 30, 2019 Category: Lipidology Authors: Funcke, J.-B., Scherer, P. E. Tags: Thematic Reviews Source Type: research
