Dietary inulin decreases circulating ceramides by suppressing neutral sphingomyelinase expression and activity in mice [Research Articles]
Elevated circulating levels of ceramides (Cers) are associated with increased risk of cardiometabolic diseases, and Cers may play a causative role in metabolic dysfunction that precedes cardiac events, such as mortality as a result of coronary artery disease. Although the mechanisms involved are likely complex, these associations suggest that lowering circulating Cer levels could be protective against cardiovascular diseases. Conversely, dietary fibers, such as inulin, have been reported to promote cardiovascular and metabolic health. However, the mechanisms involved in these protective processes also are not well understo...
Source: The Journal of Lipid Research - December 31, 2019 Category: Lipidology Authors: Deng, P., Hoffman, J. B., Petriello, M. C., Wang, C.-Y., Li, X.-S., Kraemer, M. P., Morris, A. J., Hennig, B. Tags: Research Articles Source Type: research
TNF-{alpha} induces acyl-CoA synthetase 3 to promote lipid droplet formation in human endothelial cells [Research Articles]
Chronic inflammation contributes to cardiovascular disease. Increased levels of the inflammatory cytokine, TNF-α, are often present in conditions associated with cardiovascular disease risk, and TNF-α induces a number of pro-atherogenic effects in macrovascular endothelial cells, including expression of adhesion molecules and chemokines, and lipoprotein uptake and transcytosis to the subendothelial tissue. However, little is known about the roles of acyl-CoA synthetases (ACSLs), enzymes that esterify free fatty acids into their acyl-CoA derivatives, or about the effects of TNF-α on ACSLs in endothelial ce...
Source: The Journal of Lipid Research - December 31, 2019 Category: Lipidology Authors: Jung, H. S., Shimizu-Albergine, M., Shen, X., Kramer, F., Shao, D., Vivekanandan-Giri, A., Pennathur, S., Tian, R., Kanter, J. E., Bornfeldt, K. E. Tags: Research Articles Source Type: research
Inhibition of sphingosine 1-phosphate lyase activates human keratinocyte differentiation and attenuates psoriasis in mice [Research Articles]
Sphingosine 1-phosphate (S1P) lyase is an intracellular enzyme that catalyzes the irreversible degradation of S1P and has been suggested as a therapeutic target for the treatment of psoriasis vulgaris. Because S1P induces differentiation of keratinocytes, we examined whether modulation of S1P lyase and altered intracellular S1P levels regulate proliferation and differentiation of human neonatal epidermal keratinocyte (HEKn) cells. To identify the physiological functions of S1P lyase in skin, we inhibited S1P lyase in HEKn cells with an S1P lyase-specific inhibitor (SLI) and with S1P lyase 1 (SGPL1)-specific siRNA (siSGPL1)...
Source: The Journal of Lipid Research - December 31, 2019 Category: Lipidology Authors: Jeon, S., Song, J., Lee, D., Kim, G.-T., Park, S.-H., Shin, D.-Y., Shin, K.-O., Park, K., Shim, S.-M., Park, T.-S. Tags: Research Articles Source Type: research
Glucometabolic consequences of acute and prolonged inhibition of fatty acid oxidation [Research Articles]
Excessive circulating FAs have been proposed to promote insulin resistance (IR) of glucose metabolism by increasing the oxidation of FAs over glucose. Therefore, inhibition of FA oxidation (FAOX) has been suggested to ameliorate IR. However, prolonged inhibition of FAOX would presumably cause lipid accumulation and thereby promote lipotoxicity. To understand the glycemic consequences of acute and prolonged FAOX inhibition, we treated mice with the carnitine palmitoyltransferase 1 (CPT-1) inhibitor, etomoxir (eto), in combination with short-term 45% high fat diet feeding to increase FA availability. Eto acutely increased gl...
Source: The Journal of Lipid Research - December 31, 2019 Category: Lipidology Authors: Lundsgaard, A.-M., Fritzen, A. M., Nicolaisen, T. S., Carl, C. S., Sjoberg, K. A., Raun, S. H., Klein, A. B., Sanchez-Quant, E., Langer, J., Orskov, C., Clemmensen, C., Tschöp, M. H., Richter, E. A., Kiens, B., Kleinert, M. Tags: Research Articles Source Type: research
LTB4 and 5-oxo-ETE from extracellular vesicles stimulate neutrophils in granulomatosis with polyangiitis [Research Articles]
In this study, we evaluated whether extracellular vesicles (EVs) circulating in the plasma of GPA patients could contribute to this process. EVs from the plasma of GPA patients in the active stage of the disease (n = 10) and healthy controls (n = 10) were isolated by ultracentrifugation and characterized by flow cytometry (CD63, CD8) and nanoparticle tracking analysis. Targeted oxylipin lipidomics of EVs was performed by HPLC-MS/MS. EV/oxylipin-induced neutrophil extracellular traps (NETs) were analyzed by confocal microscopy, and released double-stranded DNA (dsDNA) was quantified by PicoGreen fluorescent dye. Reactive ox...
Source: The Journal of Lipid Research - December 31, 2019 Category: Lipidology Authors: Surmiak, M., Gielicz, A., Stojkov, D., Szatanek, R., Wawrzycka-Adamczyk, K., Yousefi, S., Simon, H.-U., Sanak, M. Tags: Research Articles Source Type: research
Erratum: Docosahexaenoic acid is both a product of and a precursor to tetracosahexaenoic acid in the rat [Errata]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - December 1, 2019 Category: Lipidology Authors: Metherel, A. H., Lacombe, R. J. S., Chouinard-Watkins, R., Bazinet, R. P. Tags: Errata Source Type: research
A genome-wide search for gene-by-obesity interaction loci of dyslipidemia in Koreans shows diverse genetic risk alleles [Patient-Oriented and Epidemiological Research]
Dyslipidemia is a well-established risk factor for CVD. Studies suggest that similar fat accumulation in a given population might result in different levels of dyslipidemia risk among individuals; for example, despite similar or leaner body composition compared with Caucasians, Asians of Korean descent experience a higher prevalence of dyslipidemia. These variations imply a possible role of gene-obesity interactions on lipid profiles. Genome-wide association studies have identified more than 500 loci regulating plasma lipids, but the interaction structure between genes and obesity traits remains unclear. We hypothesized th...
Source: The Journal of Lipid Research - December 1, 2019 Category: Lipidology Authors: Kang, M., Sung, J. Tags: Patient-Oriented and Epidemiological Research Source Type: research
Potent reduction of plasma lipoprotein (a) with an antisense oligonucleotide in human subjects does not affect ex vivo fibrinolysis [Patient-Oriented and Epidemiological Research]
In conclusion, potent reductions of Lp(a) in patients with highly elevated Lp(a) levels do not affect ex vivo measures of fibrinolysis; the relevance of any putative antifibrinolytic effects of Lp(a) in vivo needs further study. (Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - December 1, 2019 Category: Lipidology Authors: Boffa, M. B., Marar, T. T., Yeang, C., Viney, N. J., Xia, S., Witztum, J. L., Koschinsky, M. L., Tsimikas, S. Tags: Patient-Oriented and Epidemiological Research Source Type: research
Investigation of diagnostic performance of five urinary cholesterol metabolites for Niemann-Pick disease type C [Patient-Oriented and Epidemiological Research]
In this study, we developed a simultaneous analysis method for five urinary conjugated cholesterol metabolites, which are potential diagnostic biomarkers for a rapid, convenient, and noninvasive chemical diagnosis, using LC/MS/MS. By the method, their urinary concentrations were quantified and the NPC diagnostic performances were evaluated. The developed LC/MS/MS method showed high accuracy and satisfied all analytical method validation criteria. When the urine of healthy controls and patients with NPC was analyzed, three of five urinary conjugated cholesterol metabolite concentrations corrected by urinary creatinine were ...
Source: The Journal of Lipid Research - December 1, 2019 Category: Lipidology Authors: Maekawa, M., Jinnoh, I., Narita, A., Iida, T., Saigusa, D., Iwahori, A., Nittono, H., Okuyama, T., Eto, Y., Ohno, K., Clayton, P. T., Yamaguchi, H., Mano, N. Tags: Patient-Oriented and Epidemiological Research Source Type: research
Insights into lipid accumulation in skeletal muscle in dysferlin-deficient mice [Research Articles]
Loss of dysferlin (DYSF) protein in humans results in limb-girdle muscular dystrophy 2B, characterized by progressive loss of muscles in the distal limbs with impaired locomotion. The DYSF-null (Bla/J) mouse develops severe steatotic muscles upon aging. Here, we report a marked increase in adipocytes, especially in the psoas and gluteus muscles but not in the soleus and tibialis anterior muscles in aged Bla/J mice compared with WT mice. There was a robust upregulation in the mRNA expression of enzymes involved in lipogenesis and triacylglycerol (TAG) synthesis pathways in the steatotic skeletal muscles. Lipidomic analysis ...
Source: The Journal of Lipid Research - December 1, 2019 Category: Lipidology Authors: Agarwal, A. K., Tunison, K., Mitsche, M. A., McDonald, J. G., Garg, A. Tags: Research Articles Source Type: research
Transfer of glucose hydrogens via acetyl-CoA, malonyl-CoA, and NADPH to fatty acids during de novo lipogenesis [Research Articles]
Deuterated water (2H2O) is widely used for measuring de novo lipogenesis (DNL). 2H is incorporated into fatty acids via exchange between body water and the hydrogens of acetyl-CoA, malonyl-CoA, and NADPH. Previous studies concluded that these exchanges are incomplete; therefore, fatty acid 2H enrichment requires correcting. In mice, we measured the 2H enrichment of fatty acid positions 2 and 3 and methyl hydrogens from [U-2H7]glucose to determine 2H transfer from glucose to fatty acid via malonyl-CoA, NADPH, and acetyl-CoA, respectively. Positional fatty acid 2H enrichments were compared with 13C enrichment of the same sit...
Source: The Journal of Lipid Research - December 1, 2019 Category: Lipidology Authors: Belew, G. D., Silva, J., Rito, J., Tavares, L., Viegas, I., Teixeira, J., Oliveira, P. J., Macedo, M. P., Jones, J. G. Tags: Research Articles Source Type: research
Decreased {omega}-6:{omega}-3 PUFA ratio attenuates ethanol-induced alterations in intestinal homeostasis, microbiota, and liver injury [Research Articles]
Ethanol (EtOH)-induced alterations in intestinal homeostasis lead to multi-system pathologies, including liver injury. -6 PUFAs exert pro-inflammatory activity, while -3 PUFAs promote anti-inflammatory activity that is mediated, in part, through specialized pro-resolving mediators [e.g., resolvin D1 (RvD1)]. We tested the hypothesis that a decrease in the -6:-3 PUFA ratio would attenuate EtOH-mediated alterations in the gut-liver axis. -3 FA desaturase-1 (fat-1) mice, which endogenously increase -3 PUFA levels, were protected against EtOH-mediated downregulation of intestinal tight junction proteins in organoid cultures an...
Source: The Journal of Lipid Research - December 1, 2019 Category: Lipidology Authors: Warner, D. R., Warner, J. B., Hardesty, J. E., Song, Y. L., King, T. N., Kang, J. X., Chen, C.-Y., Xie, S., Yuan, F., Prodhan, M. A. I., Ma, X., Zhang, X., Rouchka, E. C., Maddipati, K. R., Whitlock, J., Li, E. C., Wang, G. P., McClain, C. J., Kirpich, I. Tags: Research Articles Source Type: research
CXCL12 promotes atherosclerosis by downregulating ABCA1 expression via the CXCR4/GSK3{beta}/{beta}-cateninT120/TCF21 pathway [Research Articles]
CXC chemokine ligand 12 (CXCL12) is a member of the CXC chemokine family and mainly acts on cell chemotaxis. CXCL12 also elicits a proatherogenic role, but the molecular mechanisms have not been fully defined yet. We aimed to reveal if and how CXCL12 promoted atherosclerosis via regulating lipid metabolism. In vitro, our data showed that CXCL12 could reduce ABCA1 expression, and it mediated cholesterol efflux from THP-1-derived macrophages to apoA-I. Data from the luciferase reporter gene and chromatin immunoprecipitation assays revealed that transcription factor 21 (TCF21) stimulated the transcription of ABCA1 via binding...
Source: The Journal of Lipid Research - December 1, 2019 Category: Lipidology Authors: Gao, J.-H., He, L.-H., Yu, X.-H., Zhao, Z.-W., Wang, G., Zou, J., Wen, F.-J., Zhou, L., Wan, X.-J., Zhang, D.-W., Tang, C.-K. Tags: Research Articles Source Type: research
The three members of the Vav family proteins form complexes that concur to foam cell formation and atherosclerosis [Research Articles]
In this study we found that Vav2 deficiency in RAW264.7 macrophages significantly diminished oxidized LDL uptake and CD36 signaling, demonstrating that each Vav protein family member was required for foam cell formation. Genetic disruption of Vav2 in ApoE-deficient C57BL/6 mice significantly inhibited the severity of atherosclerosis. Strikingly, we further found that the genetic deletion of each member of the Vav protein family by CRISPR/Cas9 resulted in a similar alteration of transcriptomic profiles of macrophages. The three members of the Vav proteins were found to form complexes, and genetic ablation of each single Vav...
Source: The Journal of Lipid Research - December 1, 2019 Category: Lipidology Authors: Huang, R., Guo, G., Lu, L., Fu, R., Luo, J., Liu, Z., Gu, Y., Yang, W., Zheng, Q., Chao, T., He, L., Wang, Y., Niu, Z., Wang, H., Lawrence, T., Malissen, M., Malissen, B., Liang, Y., Zhang, L. Tags: Research Articles Source Type: research
Epoxyeicosatrienoic acid (EET)-stimulated angiogenesis is mediated by epoxy hydroxyeicosatrienoic acids (EHETs) formed from COX-2 [Research Articles]
This study further defines a role for COX-2 in mediating endothelial EET metabolism promoting angiogenesis. Using human aortic endothelial cells (HAECs), we quantified 8,9-EET-induced tube formation and cell migration as indicators of angiogenic potential in the presence and absence of a COX-2 inducer [phorbol 12,13-dibutyrate (PDBu)]. The angiogenic response to 8,9-EET in the presence of PDBu was 3-fold that elicited by 8,9-EET stabilized with a soluble epoxide hydrolase inhibitor (t-TUCB). Contributing to this response was the COX-2 metabolite of 8,9-EET, the 11-hydroxy-8,9-EET (8,9,11-EHET), which exogenously enhanced a...
Source: The Journal of Lipid Research - December 1, 2019 Category: Lipidology Authors: Rand, A. A., Rajamani, A., Kodani, S. D., Harris, T. R., Schlatt, L., Barnych, B., Passerini, A. G., Hammock, B. D. Tags: Research Articles Source Type: research
