In Memoriam: Shozo Yamamoto (1933-2020) [Tribute]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - September 30, 2020 Category: Lipidology Authors: Yamamoto, K., Ueda, N. Tags: Tribute Source Type: research
Time for a detente in the war on the mechanism of cellular fatty acid uptake [Letters to the Editor]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - August 31, 2020 Category: Lipidology Authors: Glatz, J. F. C., Luiken, J. J. F. P. Tags: Letters to the Editor Source Type: research
Esterification of 4{beta}-hydroxycholesterol and other oxysterols in human plasma occurs independently of LCAT [Patient-Oriented and Epidemiological Research]
The acyltransferase LCAT mediates FA esterification of plasma cholesterol. In vitro studies have shown that LCAT also FA-esterifies several oxysterols, but in vivo evidence is lacking. Here, we measured both free and FA-esterified forms of sterols in 206 healthy volunteers and 8 individuals with genetic LCAT deficiency, including familial LCAT deficiency (FLD) and fish-eye disease (FED). In the healthy volunteers, the mean values of the ester-to-total molar ratios of the following sterols varied: 4β-hydroxycholesterol (4βHC), 0.38; 5,6α-epoxycholesterol (5,6αEC), 0.46; 5,6β-epoxycholesterol (5,6&...
Source: The Journal of Lipid Research - August 31, 2020 Category: Lipidology Authors: Yamamuro, D., Yamazaki, H., Osuga, J.-i., Okada, K., Wakabayashi, T., Takei, A., Takei, S., Takahashi, M., Nagashima, S., Holleboom, A. G., Kuroda, M., Bujo, H., Ishibashi, S. Tags: Patient-Oriented and Epidemiological Research Source Type: research
Angiopoietin-like protein 3 governs LDL-cholesterol levels through endothelial lipase-dependent VLDL clearance [Research Articles]
Angiopoietin-like protein (ANGPTL)3 regulates plasma lipids by inhibiting LPL and endothelial lipase (EL). ANGPTL3 inactivation lowers LDL-C independently of the classical LDLR-mediated pathway and represents a promising therapeutic approach for individuals with homozygous familial hypercholesterolemia due to LDLR mutations. Yet, how ANGPTL3 regulates LDL-C levels is unknown. Here, we demonstrate in hyperlipidemic humans and mice that ANGPTL3 controls VLDL catabolism upstream of LDL. Using kinetic, lipidomic, and biophysical studies, we show that ANGPTL3 inhibition reduces VLDL-lipid content and size, generating remnant pa...
Source: The Journal of Lipid Research - August 31, 2020 Category: Lipidology Authors: Adam, R. C., Mintah, I. J., Alexa-Braun, C. A., Shihanian, L. M., Lee, J. S., Banerjee, P., Hamon, S. C., Kim, H. I., Cohen, J. C., Hobbs, H. H., Van Hout, C., Gromada, J., Murphy, A. J., Yancopoulos, G. D., Sleeman, M. W., Gusarova, V. Tags: Research Articles Source Type: research
Generation and characterization of LPA-KIV9, a murine monoclonal antibody binding a single site on apolipoprotein (a) [Research Articles]
In conclusion, the generation of monoclonal antibody LPA-KIV9 may be a useful reagent in basic research studies and in the clinical application of Lp(a) measurements. (Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - August 31, 2020 Category: Lipidology Authors: Gonen, A., Yang, X., Yeang, C., Alekseeva, E., Koschinsky, M., Witztum, J. L., Boffa, M., Tsimikas, S. Tags: Research Articles Source Type: research
Prognostic utility of triglyceride-rich lipoprotein-related markers in patients with coronary artery disease [Research Articles]
This study aimed to examine the associations of TRL-C, RLP-C, and apoC-III with incident cardiovascular events (CVEs) in the setting of secondary prevention of CAD. Plasma TRL-C, RLP-C, and total apoC-III were directly measured. A total of 4,355 participants with angiographically confirmed CAD were followed up for the occurrence of CVEs. During a median follow-up period of 5.1 years (interquartile range: 3.9–6.4 years), 543 (12.5%) events occurred. Patients with incident CVEs had significantly higher levels of TRL-C, RLP-C, and apoC-III than those without events. Multivariable Cox analysis indicated that a log unit i...
Source: The Journal of Lipid Research - August 31, 2020 Category: Lipidology Authors: Cao, Y.-X., Zhang, H.-W., Jin, J.-L., Liu, H.-H., Zhang, Y., Xu, R.-X., Gao, Y., Guo, Y.-L., Zhu, C.-G., Hua, Q., Li, Y.-F., Santos, R. D., Wu, N.-Q., Li, J.-J. Tags: Research Articles Source Type: research
ANGPTL4 inactivates lipoprotein lipase by catalyzing the irreversible unfolding of LPLs hydrolase domain [Images In Lipid Research]
(Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - August 31, 2020 Category: Lipidology Authors: Kristensen, K. K., Leth-Espensen, K. Z., Young, S. G., Ploug, M. Tags: Images In Lipid Research Source Type: research
Unlabeled lysophosphatidic acid receptor binding in free solution as determined by a compensated interferometric reader [Methods]
In conclusion, FSA-CIR offers a new increased-throughput approach to assess quantitatively label-free lipid ligand-receptor binding, including nonactivating antagonist binding, under near-native conditions. (Source: The Journal of Lipid Research)
Source: The Journal of Lipid Research - July 31, 2020 Category: Lipidology Authors: Ray, M., Nagai, K., Kihara, Y., Kussrow, A., Kammer, M. N., Frantz, A., Bornhop, D. J., Chun, J. Tags: Methods Source Type: research
Yeast phosphatidic acid phosphatase Pah1 hops and scoots along the membrane phospholipid bilayer [Research Articles]
PA phosphatase, encoded by PAH1 in the yeast Saccharomyces cerevisiae, catalyzes the Mg2+-dependent dephosphorylation of PA, producing DAG at the nuclear/ER membrane. This enzyme plays a major role in triacylglycerol synthesis and in the regulation of phospholipid synthesis. As an interfacial enzyme, PA phosphatase interacts with the membrane surface, binds its substrate, and catalyzes its reaction. The Triton X-100/PA-mixed micellar system has been utilized to examine the activity and regulation of yeast PA phosphatase. This system, however, does not resemble the in vivo environment of the membrane phospholipid bilayer. W...
Source: The Journal of Lipid Research - July 31, 2020 Category: Lipidology Authors: Kwiatek, J. M., Carman, G. M. Tags: Research Articles Source Type: research
Locations and contributions of the phosphotransferases EPT1 and CEPT1 to the biosynthesis of ethanolamine phospholipids [Research Articles]
The final step of the CDP-ethanolamine pathway is catalyzed by ethanolamine phosphotransferase 1 (EPT1) and choline/EPT1 (CEPT1). These enzymes are likely involved in the transfer of ethanolamine phosphate from CDP-ethanolamine to lipid acceptors such as 1,2-diacylglycerol (DAG) for PE production and 1-alkyl-2-acyl-glycerol (AAG) for the generation of 1-alkyl-2-acyl-glycerophosphoethanolamine. Here, we investigated the intracellular location and contribution to ethanolamine phospholipid (EP) biosynthesis of EPT1 and CEPT1 in HEK293 cells. Immunohistochemical analyses revealed that EPT1 localizes to the Golgi apparatus and ...
Source: The Journal of Lipid Research - July 31, 2020 Category: Lipidology Authors: Horibata, Y., Ando, H., Sugimoto, H. Tags: Research Articles Source Type: research
Angiopoietin-like protein 8 differentially regulates ANGPTL3 and ANGPTL4 during postprandial partitioning of fatty acids [Research Articles]
Angiopoietin-like protein (ANGPTL)8 has been implicated in metabolic syndrome and reported to regulate adipose FA uptake through unknown mechanisms. Here, we studied how complex formation of ANGPTL8 with ANGPTL3 or ANGPTL4 varies with feeding to regulate LPL. In human serum, ANGPTL3/8 and ANGPTL4/8 complexes both increased postprandially, correlated negatively with HDL, and correlated positively with all other metabolic syndrome markers. ANGPTL3/8 also correlated positively with LDL-C and blocked LPL-facilitated hepatocyte VLDL-C uptake. LPL-inhibitory activity of ANGPTL3/8 was >100-fold more potent than that of ANGPTL3...
Source: The Journal of Lipid Research - July 31, 2020 Category: Lipidology Authors: Chen, Y. Q., Pottanat, T. G., Siegel, R. W., Ehsani, M., Qian, Y.-W., Zhen, E. Y., Regmi, A., Roell, W. C., Guo, H., Luo, M. J., Gimeno, R. E., vant Hooft, F., Konrad, R. J. Tags: Research Articles Source Type: research
Crystal structure of human lysosomal acid lipase and its implications in cholesteryl ester storage disease [Research Articles]
Lysosomal acid lipase (LAL) is a serine hydrolase that hydrolyzes cholesteryl ester (CE) and TGs delivered to the lysosomes into free cholesterol and fatty acids. LAL deficiency due to mutations in the LAL gene (LIPA) results in accumulation of TGs and cholesterol esters in various tissues of the body leading to pathological conditions such as Wolman’s disease and CE storage disease (CESD). Here, we present the first crystal structure of recombinant human LAL (HLAL) to 2.6 Å resolution in its closed form. The crystal structure was enabled by mutating three of the six potential glycosylation sites. The overall s...
Source: The Journal of Lipid Research - July 31, 2020 Category: Lipidology Authors: Rajamohan, F., Reyes, A. R., Tu, M., Nedoma, N. L., Hoth, L. R., Schwaid, A. G., Kurumbail, R. G., Ward, J., Han, S. Tags: Research Articles Source Type: research
The protein kinase PknB negatively regulates biosynthesis and trafficking of mycolic acids in mycobacteria [Research Articles]
Mycobacterium tuberculosis is the causative agent of tuberculosis and remains one of the most widespread and deadliest bacterial pathogens in the world. A distinguishing feature of mycobacteria that sets them apart from other bacteria is the unique architecture of their cell wall, characterized by various species-specific lipids, most notably mycolic acids (MAs). Therefore, targeted inhibition of enzymes involved in MA biosynthesis, transport, and assembly has been extensively explored in drug discovery. Additionally, more recent evidence suggests that many enzymes in the MA biosynthesis pathway are regulated by kinase-med...
Source: The Journal of Lipid Research - July 31, 2020 Category: Lipidology Authors: Le, N.-H., Locard-Paulet, M., Stella, A., Tomas, N., Molle, V., Burlet-Schiltz, O., Daffe, M., Marrakchi, H. Tags: Research Articles Source Type: research
The lipid transfer properties of CETP define the concentration and composition of plasma lipoproteins [Research Articles]
Cholesteryl ester transfer protein (CETP) facilitates the net transfer of cholesteryl esters (CEs) and TGs between lipoproteins, impacting the metabolic fate of these lipoproteins. Previous studies have shown that a CETP antibody can alter CETP’s preference for CE versus TG as transfer substrate, suggesting that CETP substrate preference can be manipulated in vivo. Hamster and human CETPs have very different preferences for CE and TG. To assess the effect of altering CETP’s substrate preference on lipoproteins in vivo, here, we expressed human CETP in hamsters. Chow-fed hamsters received adenoviruses expressing...
Source: The Journal of Lipid Research - July 31, 2020 Category: Lipidology Authors: Morton, R. E., Liu, Y. Tags: Research Articles Source Type: research
Aging and plasma triglyceride metabolism [Reviews]
The risk for metabolic disease, including metabolic syndrome, insulin resistance, and diabetes, increases with age. Altered plasma TG metabolism and changes in fatty acid partitioning are also major contributors to metabolic disease. Plasma TG metabolism itself is altered by age in humans and rodents. As discussed in this review, the age-induced changes in human TG metabolism include increased plasma TG levels, reduced postprandial plasma TG clearance rates, reduced postheparin LPL activity, decreased adipose tissue lipolysis, and elevated ectopic fat deposition, all of which could potentially contribute to age-associated ...
Source: The Journal of Lipid Research - July 31, 2020 Category: Lipidology Authors: Spitler, K. M., Davies, B. S. J. Tags: Reviews Source Type: research
