Harmonized procedures lead to comparable quantification of total oxylipins across laboratories [Research Articles]
Oxylipins are potent lipid mediators involved in a variety of physiological processes. Their profiling has the potential to provide a wealth of information regarding human health and disease and is a promising technology for translation into clinical applications. However, results generated by independent groups are rarely comparable, which increases the need for the implementation of internationally agreed upon protocols. We performed an interlaboratory comparison for the MS-based quantitative analysis of total oxylipins. Five independent laboratories assessed the technical variability and comparability of 133 oxylipins u...
Source: The Journal of Lipid Research - November 1, 2020 Category: Lipidology Authors: Mainka, M., Dalle, C., Petera, M., Dalloux-Chioccioli, J., Kampschulte, N., Ostermann, A. I., Rothe, M., Bertrand-Michel, J., Newman, J. W., Gladine, C., Schebb, N. H. Tags: Research Articles Source Type: research

Assessing the role of glycosphingolipids in the phenotype severity of Fabry disease mouse model [Research Articles]
In this study, we compared Gb3 isoforms (various fatty acids) and lyso-Gb3 analogs (various sphingosine modifications) in two strains of Fabry disease mouse models: a pure C57BL/6 (B6) background or a B6/129 mixed background, with the latter exhibiting more prominent cardiac and renal hypertrophy and thermosensation deficits. Total Gb3 and lyso-Gb3 levels in the heart, kidney, and dorsal root ganglion (DRG) were similar in the two strains. However, levels of the C20-fatty acid isoform of Gb3 and particular lyso-Gb3 analogs (+18, +34) were significantly higher in Fabry-B6/129 heart tissue when compared with Fabry-B6. By con...
Source: The Journal of Lipid Research - November 1, 2020 Category: Lipidology Authors: Jabbarzadeh-Tabrizi, S., Boutin, M., Day, T. S., Taroua, M., Schiffmann, R., Auray-Blais, C., Shen, J.-S. Tags: Research Articles Source Type: research

Characterization of essential domains in HSD17B13 for cellular localization and enzymatic activity [Research Articles]
In conclusion, we identified critical domains and amino acid sites that are essential for the LD localization and protein function of HSD17B13, which may facilitate understanding of its function and targeting of this protein to treat chronic liver diseases. (Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - November 1, 2020 Category: Lipidology Authors: Ma, Y., Karki, S., Brown, P. M., Lin, D. D., Podszun, M. C., Zhou, W., Belyaeva, O. V., Kedishvili, N. Y., Rotman, Y. Tags: Research Articles Source Type: research

Myc linked to dysregulation of cholesterol transport and storage in nonsmall cell lung cancer [Research Articles]
Nonsmall cell lung cancer (NSCLC) is a leading cause of cancer-related deaths. While mutations in Kras and overexpression of Myc are commonly found in patients, the role of altered lipid metabolism in lung cancer and its interplay with oncogenic Myc is poorly understood. Here we use a transgenic mouse model of Kras-driven lung adenocarcinoma with reversible activation of Myc combined with surface analysis lipid profiling of lung tumors and transcriptomics to study the effect of Myc activity on cholesterol homeostasis. Our findings reveal that the activation of Myc leads to the accumulation of cholesteryl esters (CEs) store...
Source: The Journal of Lipid Research - November 1, 2020 Category: Lipidology Authors: Hall, Z., Wilson, C. H., Burkhart, D. L., Ashmore, T., Evan, G. I., Griffin, J. L. Tags: Research Articles Source Type: research

Brown adipose tissue lipoprotein and glucose disposal is not determined by thermogenesis in uncoupling protein 1-deficient mice [Research Articles]
Adaptive thermogenesis is highly dependent on uncoupling protein 1 (UCP1), a protein expressed by thermogenic adipocytes present in brown adipose tissue (BAT) and white adipose tissue (WAT). Thermogenic capacity of human and mouse BAT can be measured by positron emission tomography-computed tomography quantifying the uptake of 18F-fluodeoxyglucose or lipid tracers. BAT activation is typically studied in response to cold exposure or treatment with β-3-adrenergic receptor agonists such as CL316,243 (CL). Currently, it is unknown whether cold-stimulated uptake of glucose or lipid tracers is a good surrogate marker of UCP...
Source: The Journal of Lipid Research - November 1, 2020 Category: Lipidology Authors: Fischer, A. W., Behrens, J., Sass, F., Schlein, C., Heine, M., Pertzborn, P., Scheja, L., Heeren, J. Tags: Research Articles Source Type: research

Chylomicronemia from GPIHBP1 autoantibodies [Reviews]
Some cases of chylomicronemia are caused by autoantibodies against glycosylphosphatidylinositol-anchored HDL binding protein 1 (GPIHBP1), an endothelial cell protein that shuttles LPL to the capillary lumen. GPIHBP1 autoantibodies prevent binding and transport of LPL by GPIHBP1, thereby disrupting the lipolytic processing of triglyceride-rich lipoproteins. Here, we review the "GPIHBP1 autoantibody syndrome" and summarize clinical and laboratory findings in 22 patients. All patients had GPIHBP1 autoantibodies and chylomicronemia, but we did not find a correlation between triglyceride levels and autoantibody levels. Many of ...
Source: The Journal of Lipid Research - November 1, 2020 Category: Lipidology Authors: Miyashita, K., Lutz, J., Hudgins, L. C., Toib, D., Ashraf, A. P., Song, W., Murakami, M., Nakajima, K., Ploug, M., Fong, L. G., Young, S. G., Beigneux, A. P. Tags: Reviews Source Type: research

Novel contact sites between lipid droplets, early endosomes, and the endoplasmic reticulum [Images in Lipid Research]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - November 1, 2020 Category: Lipidology Authors: Parton, R. G., Bosch, M., Steiner, B., Pol, A. Tags: Images in Lipid Research Source Type: research

Lipid sensing tips the balance for a key cholesterol synthesis enzyme [Images in Lipid Research]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - November 1, 2020 Category: Lipidology Authors: Chua, N. K., Brown, A. J. Tags: Images in Lipid Research Source Type: research

A closer look at the mysterious HSD17B13 [Commentary]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - November 1, 2020 Category: Lipidology Authors: Dong, X. C. Tags: Commentary Source Type: research

The structural basis for monoclonal antibody 5D2 binding to the tryptophan-rich loop of lipoprotein lipase [Research Articles]
For three decades, the LPL–specific monoclonal antibody 5D2 has been used to investigate LPL structure/function and intravascular lipolysis. 5D2 has been used to measure LPL levels, block the triglyceride hydrolase activity of LPL, and prevent the propensity of concentrated LPL preparations to form homodimers. Two early studies on the location of the 5D2 epitope reached conflicting conclusions, but the more convincing report suggested that 5D2 binds to a tryptophan (Trp)-rich loop in the carboxyl terminus of LPL. The same loop had been implicated in lipoprotein binding. Using surface plasmon resonance, we showed that...
Source: The Journal of Lipid Research - September 30, 2020 Category: Lipidology Authors: Luz, J. G., Beigneux, A. P., Asamoto, D. K., He, C., Song, W., Allan, C. M., Morales, J., Tu, Y., Kwok, A., Cottle, T., Meiyappan, M., Fong, L. G., Kim, J. E., Ploug, M., Young, S. G., Birrane, G. Tags: Research Articles Source Type: research

Different rates of flux through the biosynthetic pathway for long-chain versus very-long-chain sphingolipids [Research Articles]
The backbone of all sphingolipids (SLs) is a sphingoid long-chain base (LCB) to which a fatty acid is N-acylated. Considerable variability exists in the chain length and degree of saturation of both of these hydrophobic chains, and recent work has implicated ceramides with different LCBs and N-acyl chains in distinct biological processes; moreover, they may play different roles in disease states and possibly even act as prognostic markers. We now demonstrate that the half-life, or turnover rate, of ceramides containing diverse N-acyl chains is different. By means of a pulse-labeling protocol using stable-isotope, deuterate...
Source: The Journal of Lipid Research - September 30, 2020 Category: Lipidology Authors: Zelnik, I. D., Volpert, G., Viiri, L. E., Kauhanen, D., Arazi, T., Aalto-Setälä, K., Laaksonen, R., Futerman, A. H. Tags: Research Articles Source Type: research

Depletion of adipocyte sphingosine kinase 1 leads to cell hypertrophy, impaired lipolysis, and nonalcoholic fatty liver disease [Research Articles]
Sphingolipids have become established participants in the pathogenesis of obesity and its associated maladies. Sphingosine kinase 1 (SPHK1), which generates S1P, has been shown to increase in liver and adipose of obese humans and mice and to regulate inflammation in hepatocytes and adipose tissue, insulin resistance, and systemic inflammation in mouse models of obesity. Previous studies by us and others have demonstrated that global sphingosine kinase 1 KO mice are protected from diet-induced obesity, insulin resistance, systemic inflammation, and NAFLD, suggesting that SPHK1 may mediate pathological outcomes of obesity. A...
Source: The Journal of Lipid Research - September 30, 2020 Category: Lipidology Authors: Anderson, A. K., Lambert, J. M., Montefusco, D. J., Tran, B. N., Roddy, P., Holland, W. L., Cowart, L. A. Tags: Research Articles Source Type: research

Serum lipoprotein (a) associates with a higher risk of reduced renal function: a prospective investigation [Research Articles]
Lipoprotein (a) [Lp(a)] is a well-known risk factor for cardiovascular disease, but analysis on Lp(a) and renal dysfunction is scarce. We aimed to investigate prospectively the association of serum Lp(a) with the risk of reduced renal function, and further investigated whether diabetic or hypertensive status modified such association. Six thousand two hundred and fifty-seven Chinese adults aged ≤40 years and free of reduced renal function at baseline were included in the study. Reduced renal function was defined as estimated glomerular filtration rate <60 ml/min/1.73 m2. During a mean follow-up of 4.4 years, 158 part...
Source: The Journal of Lipid Research - September 30, 2020 Category: Lipidology Authors: Xuan, L., Wang, T., Dai, H., Wang, B., Xiang, J., Wang, S., Lin, H., Li, M., Zhao, Z., Lu, J., Chen, Y., Xu, Y., Wang, W., Xu, M., Bi, Y., Ning, G. Tags: Research Articles Source Type: research

Interleukin 6 reduces allopregnanolone synthesis in the brain and contributes to age-related cognitive decline in mice [Research Articles]
Cognitive decline with age is a harmful process that can reduce quality of life. Multiple factors have been established to contribute to cognitive decline, but the overall etiology remains unknown. Here, we hypothesized that cognitive dysfunction is mediated, in part, by increased levels of inflammatory cytokines that alter allopregnanolone (AlloP) levels, an important neurosteroid in the brain. We assessed the levels and regulation of AlloP and the effects of AlloP supplementation on cognitive function in 4-month-old and 24-month-old male C57BL/6 mice. With age, the expression of enzymes involved in the AlloP synthetic pa...
Source: The Journal of Lipid Research - September 30, 2020 Category: Lipidology Authors: Parks, E. E., Logan, S., Yeganeh, A., Farley, J. A., Owen, D. B., Sonntag, W. E. Tags: Research Articles Source Type: research

Accessibility of cholesterol at cell surfaces [Images In Lipid Research]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - September 30, 2020 Category: Lipidology Authors: Johnson, K. A., Radhakrishnan, A. Tags: Images In Lipid Research Source Type: research