Phospholipid Transfer Research Articles

Proteomics-based identification and validation of novel plasma biomarkers phospholipid transfer protein and mannan-binding lectin serine protease-1 in age-related macular degeneration.

Age-related macular degeneration (AMD) is a major cause of severe, progressive visual loss among the elderly. There are currently no established serological markers for the diagnosis of AMD. In this study, we carried out a large-scale quantitative proteomics analysis to identify plasma proteins that could serve as potential AMD biomarkers. We found that the plasma levels of phospholipid transfer protein (PLTP) and mannan-binding lectin serine protease (MASP)-1 were increased in AMD patients relative to controls. The receiver operating characteristic curve based on data from an independent set of AMD patients and healthy controls had an area under the curve of 0.936 for PLTP and 0.716 for MASP-1, revealing excellent discrimination between the two groups. A proteogenomic combination model that incorporated PLTP and MASP-1 along with two known risk genotypes of age-related maculopathy susceptibility 2 and complement factor H genes further enhanced discriminatory power. Additionally, PLTP and MASP-1 mRNA and protein expression levels were upregulated in retinal pigment epithelial cells upon exposure to oxidative stress in vitro. These results indicate that PLTP and MASP-1 can serve as plasma biomarkers for the early diagnosis and treatment of AMD, which is critical for preventing AMD-related blindness.

Plasma phospholipid transfer protein activity is inversely associated with betaine in diabetic and non-diabetic subjects.

BackgroundThe choline metabolite, betaine, plays a role in lipid metabolism, and may predict the development of cardiovascular disease and type 2 diabetes mellitus (T2DM). Phospholipid transfer protein (PLTP) and lecithin:cholesterol acyltransferase (LCAT) require phosphatidylcholine as substrate, raising the possibility that there is an intricate relationship of these protein factors with choline metabolism. Here we determined the relationships of PLTP and LCAT activity with betaine in subjects with and without T2DM.MethodsPlasma betaine (nuclear magnetic resonance spectroscopy), PLTP activity (liposome-vesicle HDL system), LCAT activity (exogenous substrate assay) and (apo)lipoproteins were measured in 65 type 2 diabetic (T2DM) and in 55 non-diabetic subjects.ResultsPLTP and LCAT activity were elevated in T2DM (p < 0.05), whereas the difference in betaine was not significant. In age-, sex- and diabetes status-controlled correlation analysis, betaine was inversely correlated with triglycerides and positively with HDL cholesterol (p < 0.05 to 0.01). PLTP and LCAT activity were positively correlated with triglycerides and inversely with HDL cholesterol (p < 0.05 to 0.001). PLTP (r = −0.245, p = 0.006) and LCAT activity (r = −0.195, p = 0.035) were correlated inversely with betaine. The inverse association of PLTP activity with betaine remained significant after additional adjustment for body mass index and lipoprotein variables (β = −0.179, p = 0.034), whereas its association with LCAT activity lost significance (β = −0.056, p = 0.44).ConclusionsBetaine may influence lipoprotein metabolism via an effect on PLTP activity.

Loss of Function of GALNT2 Lowers High-Density Lipoproteins in Humans, Nonhuman Primates, and Rodents

Human genetics studies have implicated GALNT2, encoding GalNAc-T2, as a regulator of high-density lipoprotein cholesterol (HDL-C) metabolism, but themechanisms relating GALNT2 to HDL-C remain unclear. We investigated the impact of homozygous GALNT2 deficiency on HDL-C in humans and mammalian models. We identified two humans homozygous for loss-of-function mutations in GALNT2 who demonstrated low HDL-C. We also found that GALNT2 loss of function in mice, rats, and nonhuman primates decreased HDL-C. O-glycoproteomics studies of a human GALNT2-deficient subject validated ANGPTL3 and ApoC-III as GalNAc-T2 targets. Additional glycoproteomics in rodents identified targets influencing HDL-C, including phospholipid transfer protein (PLTP). GALNT2 deficiency reduced plasma PLTP activity in humans and rodents, and in mice this was rescued by reconstitution of hepatic Galnt2. We also found that GALNT2 GWAS SNPs associated with reduced HDL-C also correlate with lower hepatic GALNT2 expression. These results posit GALNT2 as a direct modulator of HDL metabolism across mammals.

A phospholipid transfer function of ER-mitochondria encounter structure revealed in vitro.

As phospholipids are synthesized mainly in the endoplasmic reticulum (ER) and mitochondrial inner membranes, how cells properly distribute specific phospholipids to diverse cellular membranes is a crucial problem for maintenance of organelle-specific phospholipid compositions. Although the ER-mitochondria encounter structure (ERMES) was proposed to facilitate phospholipid transfer between the ER and mitochondria, such a role of ERMES is still controversial and awaits experimental demonstration. Here we developed a novel in vitro assay system with isolated yeast membrane fractions to monitor phospholipid exchange between the ER and mitochondria. With this system, we found that phospholipid transport between the ER and mitochondria relies on membrane intactness, but not energy sources such as ATP, GTP or the membrane potential across the mitochondrial inner membrane. We further found that lack of the ERMES component impairs the phosphatidylserine transport from the ER to mitochondria, but not the phosphatidylethanolamine transport from mitochondria to the ER. This in vitro assay system thus offers a powerful tool to analyze the non-vesicular phospholipid transport between the ER and mitochondria.

Cigarette smoke extract alters the cell cycle via the phospholipid transfer protein/transforming growth factor-β1/CyclinD1/CDK4 pathway

This study was aimed to investigate the effect of phospholipid transfer protein (PLTP) on cigarette smoke extract (CSE)-induced alteration of the cell cycle and the possible mechanism. Male Wistar rats and the rat alveolar epithelial cell line (RLE-6TN) were exposed to normal air or different concentrations of CSE. Then PLTP siRNA was transfected into cells and an inhibitor of transforming growth factor-β1 (TGF-β1) was administered prior to CSE exposure. Histological changes and cell cycle stage were recorded, as were the expression levels of PLTP, TGF-β1, CyclinD1 and CDK4. Resulting morphological changes included diffuse interstitial substance incrassation and elevated alveolar rupturing. Flow cytometry analysis revealed an increase in the number of cells in the G1 phase in a time- and dose-related manner. Both PLTP and TGF-β1 were up-regulated at protein and mRNA levels, whereas CyclinD1 and CDK4 expression was down-regulated after CSE exposure. Furthermore, PLTP siRNA significantly suppressed CSE-induced TGF-β1 expression, resulting in up-regulation of CyclinD1 and CDK4, but the TGF-β1 inhibitor was not able to abrogate CSE-induced PLTP over-expression. In conclusion, PLTP may operate upstream of the TGF-β1/CyclinD1/CDK4 pathway and may mediate the CSE-induced G1 arrest in RLE-6TN cells. Our work provides some new insight into the relation between PLTP and cell cycle progression.

MICOS and phospholipid transfer by Ups2-Mdm35 organize membrane lipid synthesis in mitochondria.

Mitochondria exert critical functions in cellular lipid metabolism and promote the synthesis of major constituents of cellular membranes, such as phosphatidylethanolamine (PE) and phosphatidylcholine. Here, we demonstrate that the phosphatidylserine decarboxylase Psd1, located in the inner mitochondrial membrane, promotes mitochondrial PE synthesis via two pathways. First, Ups2-Mdm35 complexes (SLMO2-TRIAP1 in humans) serve as phosphatidylserine (PS)-specific lipid transfer proteins in the mitochondrial intermembrane space, allowing formation of PE by Psd1 in the inner membrane. Second, Psd1 decarboxylates PS in the outer membrane in trans, independently of PS transfer by Ups2-Mdm35. This latter pathway requires close apposition between both mitochondrial membranes and the mitochondrial contact site and cristae organizing system (MICOS). In MICOS-deficient cells, limiting PS transfer by Ups2-Mdm35 and reducing mitochondrial PE accumulation preserves mitochondrial respiration and cristae formation. These results link mitochondrial PE metabolism to MICOS, combining functions in protein and lipid homeostasis to preserve mitochondrial structure and function.

The effect of phospholipid transfer protein on cigarette smoke extract induced epithelial-mesenchymal transition of rat alveolar type Ⅱ cells

To investigate the effect of phospholipid transfer protein(PLTP) on cigarette smoke extract(CSE) induced epithelial-mesenchymal transition(EMT) in rat alveolar Type Ⅱ cells (RLE-6TN). CSE of different concentrations (0%, 0.25%, 0.5% and 1%) was co-cultured for 2 or 3 days with RLE-6TN, either pre-treated or not pre-treated with siRNA-PLTP for 6 h. Expression levels of E-cadherin mRNA and Vimentin mRNA were examined by RT-PCR, while expression levels of PLTP, E-cadherin, N-cadherin and Vimentin were examined by Western blot. Our results showed that the expression of E-cadherin mRNA decreased in CSE-treated groups: 1.01±0.05, 0.74±0.05, 0.65±0.03, 0.30±0.08 respectively at different concentrations of CSE (0 %, 0.25%, 0.5 %, and 1.0%); while the level of Vimentin mRNA increased significantly in 1% CSE treated cells(1.88±0.49), compared with control cells (1.01±0.20). Treatment with CSE at different concentrations (0%, 0.25%, 0.5% and 1%) showed that the protein levels of PLTP were 0.42±0.02, 0.89±0.25, 1.08±0.18, 1.61±0.06 respectively; those of E-cadherin were 1.61±0.04, 1.08±0.10, 0.62±0.08, 0.68±0.17, respectively; those of N-cadherin were 0.60±0.14, 0.57±0.26, 0.88±0.30, 1.94±0.54, respectively; and those of Vimentin were 0.61±0.05, 0.98±0.16, 1.07±0.14, 1.34±0.19, respectively; all P<0.05 when the 1% CSE group was compared with the control group. EMT induced by CSE was significantly inhibited by siRNA-PLTP. PLTP may be involved in CSE induced EMT of rat alveolar cells.

Endoplasmic reticulum-mediated signalling in cellular microdomains.

The endoplasmic reticulum (ER) is a prime mediator of cellular signalling due to its functions as an internal cellular store for calcium, as well as a site for synthesis of proteins and lipids. Its peripheral network of sheets and tubules facilitates calcium and lipid signalling, especially in areas of the cell that are more distant to the main cytoplasmic network. Specific membrane proteins shape the peripheral ER architecture and influence the network stability to project into restricted spaces. The signalling microdomains are anatomically separate from the cytoplasm as a whole and exhibit localized protein, ion channel and cytoskeletal element expression. Signalling can also occur between the ER and other organelles, such as the Golgi or mitochondria. Lipids made in the ER membrane can be sent to the Golgi via specialized transfer proteins and specific phospholipid synthases are enriched at ER-mitochondria junctions to more efficiently expedite phospholipid transfer. As a hub for protein and lipid synthesis, a store for intracellular calcium [Ca2+ ]i and a mediator of cellular stress, the ER is an important cellular organelle. Its ability to organize into tubules and project into restricted spaces allows for discrete and temporal signalling, which is important for cellular physiology and organism homoeostasis.

Phospholipid transfer protein deficiency in mice impairs macrophage reverse cholesterol transport invivo.

Phospholipid transfer protein is expressed in various cell types and secreted into plasma, where it transfers phospholipids between lipoproteins and modulates the composition of high-density lipoprotein particles. Phospholipid transfer protein deficiency invivo can lower high-density lipoprotein cholesterol level significantly and impact the biological quality of high-density lipoprotein. Considering high-density lipoprotein was a critical determinant for reverse cholesterol transport, we investigated the role of systemic phospholipid transfer protein deficiency in macrophage reverse cholesterol transport invivo After the littermate phospholipid transfer protein KO and WT mice were fed high-fat diet for one month, they were injected intraperitoneally with (3)H-cholesterol-labeled and acLDL-loaded macrophages. Then the appearance of (3)H-tracer in plasma, liver, bile, intestinal wall, and feces over 48 h was determined. Plasma lipid analysis indicated phospholipid transfer protein deficiency lowered total cholesterol, high-density lipoprotein-C and apolipoprotein A1 levels significantly but increased triglyceride level in mice. The isotope tracing experiment showed (3)H-cholesterol of plasma was decreased by 68% for male and 62% for female, and (3)H-tracer of bile was decreased by 37% for male and 21% for female in phospholipid transfer protein KO mice compared with WT mice. However, there was no difference in liver, and (3)H-tracer of intestinal wall was increased by 43% for male and 27% for female. Finally, (3)H-tracer of fecal excretion in phospholipid transfer protein KO mice was reduced significantly by 36% for male and 43% for female during 0-24 h period, but there was no significant difference during 24-48 h period. Meanwhile, Western Blot analysis showed the expressions of reverse cholesterol transport -related protein liver X receptor α (LXRα), ATP binding cassette transporter A1, and cholesterol 7α-hydroxylase A1 were upregulated in liver of phospholipid transfer protein KO mice compared with WT mice. These data reveal that systemic phospholipid transfer protein deficiency in mice impairs macrophage-specific reverse cholesterol transport invivo.

A Novel Non-specific Lipid Transfer Protein Gene from Sugarcane (NsLTPs), Obviously Responded to Abiotic Stresses and Signaling Molecules of SA and MeJA

Non-specific lipid transfer proteins (NsLTPs) are soluble, small, basic proteins in plant, which have been reported to be involved in plant physiological functions such as the catalyzing transfer of phospholipids and play an important role in plant defense and stress responses. In this study, a member of NsLTP family gene (ScNsLTP, Acc. No. KR259657) was isolated from a full-length cDNA library of sugarcane stalk. The cDNA of ScNsLTP was 671 bp long and contained a 312 bp open reading frame (ORF), which can encode a protein of 103 amino acid residues with molecular weight of 10.66 kDa. The ScNsLTP transcript levels in sugarcane seedlings decreased in response to SA, whereas it increased under MeJA treatment, suggesting an antagonistic regulatory mechanism between the signaling molecules of SA and MeJA. The transcript levels of ScNsLTP were obviously up-regulated under chilling and PEG stresses, implying that the ScNsLTP gene was involved in response to abiotic stresses and playing a positive role in adaption to low temperature and drought stresses. These results provide important information for further functional studies of plant NsLTPs gene.

Pathways for Modulating Exosome Lipids Identified By High-Density Lipoprotein-Like Nanoparticle Binding to Scavenger Receptor Type B-1.

Exosomes are produced by cells to mediate intercellular communication, and have been shown to perpetuate diseases, including cancer. New tools are needed to understand exosome biology, detect exosomes from specific cell types in complex biological media, and to modify exosomes. Our data demonstrate a cellular pathway whereby membrane-bound scavenger receptor type B-1 (SR-B1) in parent cells becomes incorporated into exosomes. We tailored synthetic HDL-like nanoparticles (HDL NP), high-affinity ligands for SR-B1, to carry a fluorescently labeled phospholipid. Data show SR-B1-dependent transfer of the fluorescent phospholipid from HDL NPs to exosomes. Modified exosomes are stable in serum and can be directly detected using flow cytometry. As proof-of-concept, human serum exosomes were found to express SR-B1, and HDL NPs can be used to label and isolate them. Ultimately, we discovered a natural cellular pathway and nanoparticle-receptor pair that enables exosome modulation, detection, and isolation.

Computational studies of plasma lipoprotein lipids

Plasma lipoproteins are macromolecular assemblies of proteins and lipids found in the blood. The lipid components of lipoproteins are amphipathic lipids such as phospholipids (PLs), and unesterified cholesterols (UCs) and hydrophobic lipids such as cholesteryl esters (CEs) and triglycerides (TGs). Since lipoproteins are soft matter supramolecular assemblies easily deformable by thermal fluctuations and they also exist in varying densities and protein/lipid components, a detailed understanding of their structure/function is experimentally difficult. Molecular dynamics (MD) simulation has emerged as a particularly promising way to explore the structure and dynamics of lipoproteins. The purpose of this review is to survey the current status of computational studies of the lipid components of the lipoproteins. Computational studies aim to explore three levels of complexity for the 3-dimensional structural dynamics of lipoproteins at various metabolic stages: (i) lipoprotein particles consist of protein with minimal lipid; (ii) lipoprotein particles consist of PL-rich discoidal bilayer-like lipid particles; (iii) mature circulating lipoprotein particles consist of CE-rich or TG-rich spheroidal lipid-droplet-like particles. Due to energy barriers involved in conversion between these species, other biomolecules also participate in lipoprotein biological assembly. For example: (i) lipid-poor apolipoprotein A-I (apoA-I) interacts with ATP-binding cassette transporter A1 (ABCA1) to produce nascent discoidal high density lipoprotein (dHDL) particles; (ii) lecithin–cholesterol acyltransferase (LCAT) mediates the conversion of UC to CE in dHDL, driving spheroidal HDL (sHDL) formation; (iii) transfer proteins, cholesterol ester transfer protein (CETP) and phospholipid transfer protein (PLTP), transfer both CE and TG and PL, respectively, between lipoprotein particles. Computational studies have the potential to explore different lipoprotein particles at each metabolic stage in atomistic detail. This review discusses the current status of computational methods including all-atom MD (AAMD), coarse-grain MD (CGMD), and MD-simulated annealing (MDSA) and their applications in lipoprotein structural dynamics and biological assemblies. Results from MD simulations are discussed and compared across studies in order to identify key findings, controversies, issues and future directions. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg.

AtMic60 Is Involved in Plant Mitochondria Lipid Trafficking and Is Part of a Large Complex

The mitochondrion is an organelle originating from an endosymbiotic event and playing a role in several fundamental processes such as energy production, metabolite syntheses, and programmed cell death. This organelle is delineated by two membranes whose synthesis requires an extensive exchange of phospholipids with other cellular organelles such as endoplasmic reticulum (ER) and vacuolar membranes in yeast. These transfers of phospholipids are thought to occur by a non-vesicular pathway at contact sites between two closely apposed membranes. In plants, little is known about the biogenesis of mitochondrial membranes. Contact sites between ER and mitochondria are suspected to play a similar role in phospholipid trafficking as in yeast, but this has never been demonstrated. In contrast, it has been shown that plastids are able to transfer lipids to mitochondria during phosphate starvation. However, the proteins involved in such transfer are still unknown. Here, we identified in Arabidopsis thaliana a large lipid-enriched complex called the mitochondrial transmembrane lipoprotein (MTL) complex. The MTL complex contains proteins located in the two mitochondrial membranes and conserved in all eukaryotic cells, such as the TOM complex and AtMic60, a component of the MICOS complex. We demonstrate that AtMic60 contributes to the export of phosphatidylethanolamine from mitochondria and the import of galactoglycerolipids from plastids during phosphate starvation. Furthermore, AtMic60 promotes lipid desorption from membranes, likely as an initial step for lipid transfer, and binds to Tom40, suggesting that AtMic60 could regulate the tethering between the inner and outer membranes of mitochondria.

Effect of stretching on PLTP secretion in alveolar epithelial TypII cell

Background: Phospholipid transfer protein (PLTP) facilitates the transfer of a spectrum of different lipid molecules, not only in the vascular compartment, but also in a variety of tissues. It is highly expressed within the lung epithelium. Alterations in lung lipid metabolism precede the development of fibrosis, at the same time inflammation likely plays a role in disease genesis and progression.

The binding capability of plasma phospholipid transfer protein, but not HDL pool size, is critical to repress LPS induced inflammation.

Phospholipid transfer protein (PLTP) participates in high density lipoprotein (HDL) metabolism. Increased plasma PLTP activity was observed in lipopolysaccharide (LPS) triggered acute inflammatory diseases. This study aimed to determine the exact role of PLTP in LPS induced inflammation. HDL pool size was shrunk both in PLTP deficient mice (PLTP−/−) and PLTP transgenic mice (PLTP-Tg). PLTP displayed a strong protective effect on lethal endotoxemia in mice survival study. Furthermore, after LPS stimulation, the expression of pro-inflammatory cytokines were increased in bone marrow derived macrophage (BMDM) from PLTP−/−, while decreased in BMDM from PLTP-Tg compared with BMDM from wild-type mice (WT). Moreover, LPS induced nuclear factor kappa-B (NFκB) activation was enhanced in PLTP−/− BMDM or PLTP knockdown RAW264.7. Conversely, PLTP overexpression countered the NFκB activation in LPS challenged BMDM. Additionally, the activation of toll like receptor 4 (TLR4) induced by LPS showed no alteration in PLTP−/− BMDM. Finally, PLTP could bind to LPS, attenuate the pro-inflammatory effects of LPS, and improve the cell viability in vitro. To sum up, these findings elucidated that PLTP repressed LPS induced inflammation due to extracellular LPS binding capability, and the protective effects were not related to HDL pool size in mice.

The Complex, Asymmetric, Escherichia Coli Envelope Studied by Neutron Scattering

The Gram-negative bacterial surface is highly complex, comprising an inner (cytoplasmic) membrane, an aqueous periplasm and a characteristic outer membrane (OM). The OM is unusually asymmetric with a phospholipid inner leaflet and lipopolysaccharide (LPS) outer leaflet. The OM acts as a molecular sieve, playing an important role in antibiotic resistance and this global problem drives an increasing need to understand the molecular structure and dynamics of the OM. However, the OM complexity has proven difficult to recreate in vitro. Here we present the formation and characterisation of floating asymmetric OM models with aqueous compartments on both sides. The asymmetry is created by Langmuir-Blodgett and Langmuir-Schaefer transfers of phospholipids and LPS respectively onto a self-assembled phospholipid monolayer (inner membrane). The structure and asymmetry were confirmed using neutron reflectivity and deuterated phospholipids. The resolution was greatly improved by the use of magnetic contrast which provides two separate reflection profiles for a single identical biological layer. The results showed that the OM models had asymmetries of over 90% and were stable for days. Three experiments compared the in vitro behaviour with published in vivo data. Firstly removal of divalent cations that stabilise the phosphate rich LPS layer showed a mixing of the LPS and phospholipid layers and a roughening of the surface. This agreed with both published in vivo data and atomistic MD simulations. Secondly, the antibacterial protein lactoferrin created water filled holes in the membrane and thirdly we confirmed that another antibacterial protein lysozyme binds to, but does not disrupt, the OM. By resembling the natural OM these models provide a robust testbed for antibiotic activity, especially colicins, polymyxins and colistins, and enables us to better understand the role of protein lipid interactions in stabilising the OM.

Bacterial Lipopolysaccharides Change Membrane Fluidity with Relevance to Phospholipid and Amyloid Beta Dynamics in Alzheimer’s Disease

Bacterial lipopolysaccharides (LPS) and their increase in plasma in individuals in the developing world has become of major concern. LPS can transform cells by their rapid insertion into cell membranes that partition into cholesterol/sphingomyelin domains. LPS alter cell phospholipid dynamics associated with the recruitment of the Alzheimer’s disease amyloid beta (Aβ) peptide with the promotion of toxic Aβ oligomer formation. The common pattern of naturally occurring phospholipids such as1-palmitoyl-2-oleolyl-phosphatidylcholine in cells confers cells with the rapid transfer of Aβ and phospholipids. Phospholipids such as dipalmitoylphosphatidylcholine (DPPC), dimyristoylphosphatidylcholine (DMPC) and dioleoylphosphatidylcholine (DOPC) are poorly transported with delayed metabolism of Aβ oligomers. LPS can alter cells with POPC cell membrane characteristics by insertion of itself and promotion of ganglioside GM1-cholesterol as the seed for Aβ oligomerization. LPS modification of cell membrane fluidity in neurons involves the phospholipid transfer protein that affects vitamin E, phospholipid and Aβ metabolism. Healthy diets that contain olive oil, canola oil and vegetable oil promote membrane fluidity and Aβ metabolism but in the developing world increased LPS levels interfere with healthy diets and their regulation of phospholipid and Aβ dynamics. Unhealthy diets that contain palmitic acid should be avoided that promote DPPC cell membrane contents with poor phospholipid and Aβ metabolism. Nutritional therapy may improve metabolic disease and Alzheimer’s disease by the delay of LPS toxic induced Aβ interactions that involve various proteins such as albumin (Aβ selfassociation) with reduced toxic effects of LPS to astrocyte-neuron crosstalk in the brain.

Serum CETP and PLTP activity in middle-aged men living in urban or rural area of the Lower Silesia region. PURE Poland sub-study.

IntroductionThe dependence of lipid transfer proteins on significant pro-atherogenic factors is unclear. The aim of the study was to evaluate serum cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) activity in relation to lipid disturbances in men living in an urban or rural area.Material and methodsA group of 427 men, volunteers for the Prospective Urban Rural Epidemiology (PURE) sub-study – 263 urban inhabitants (aged 51.9 ±6.0) and 164 residents of villages (aged 51.1 ±5.9) – were examined. In the multivariable linear regression model, the following factors were included as potential confounders: age, body mass index (BMI), smoking, alcohol consumption, hs-C-reactive protein reaction (hs-CRP) and co-existence of chronic diseases.ResultsIn multiple linear regression models, site of residence (urban or rural area) was the most important independent and consistent predictor of CETP and PLTP activity; β coefficients (95% CI) for CETP (0.18) and PLTP (–0.29) were significant at levels of p < 0.001. Three-way analysis of variance showed no effect of smoking or moderate alcohol consumption on lipid transfer proteins; however, CETP activity showed an interaction effect between these risk factors. In the group of all men, CETP activity was significantly and positively correlated with total cholesterol (r = 0.24), low-density lipoprotein cholesterol (r = 0.18), and non-high density lipoprotein cholesterol (r = 0.21), whereas PLTP activity was correlated with BMI (r = 0.12). Body mass index in rural men was higher than in the urban male population.ConclusionsIncreased PLTP activity, recognized as a pro-atherogenic factor, and decreased CETP activity, known as a protective factor, both observed in men living in rural areas, are probably conditioned by nutritional and/or genetic factors.

Silencing of &lt;i&gt;Nicotiana benthamiana&lt;/i&gt; SEC14 phospholipid transfer protein reduced jasmonic acid dependent defense against &lt;i&gt;Pseudomonas syringae&lt;/i&gt;

Silencing of &lt;i&gt;Nicotiana benthamiana&lt;/i&gt; SEC14 phospholipid transfer protein reduced jasmonic acid dependent defense against &lt;i&gt;Pseudomonas syringae&lt;/i&gt;

Exchanging carbohydrate or protein for fat improves lipid-related cardiovascular risk profile in overweight men and women when consumed ad libitum.

The impact of low-fat diets on the plasma lipoprotein profile is incompletely understood. We conducted two 16-week dietary studies to compare the effects of a moderate-fat (mod-FAT) baseline diet with isocaloric and ad libitum low-fat diets rich in either carbohydrates (high-CHO, n = 16) or protein (high-PRO, n = 19) on plasma lipids, post-heparin lipase activities, cholesteryl ester transfer protein, and phospholipid transfer protein. Switching from the mod-FAT to the isocaloric high-CHO diet lowered plasma high-density lipoprotein cholesterol concentrations (P < 0.001) and tended to increase triglyceride levels (P = 0.087). Cholesterol content in the larger, buoyant low-density lipoprotein (LDL) fractions decreased, whereas those of the very-low-density lipoprotein, intermediate-density lipoprotein, and smaller, denser LDL fractions tended to increase. These changes were largely reversed when subjects lost weight by consuming this high-CHO diet ad libitum. Switching from the mod-FAT diet to the isocaloric high-PRO diet did not increase cholesterol content in the small-dense LDL fraction and led to decreases in both LDL and high-density lipoprotein cholesterol in plasma (P < 0.001 for both).Consumption of the high-protein ad libitum diet accompanied by weight loss did not change plasma lipids further, except for a shift of cholesterol from dense low-density lipoprotein fractions to more buoyant low-density lipoprotein fractions. Cholesteryl ester transfer protein concentrations decreased with high-cholesterol feeding, whereas cholesteryl ester transfer protein concentrations and hepatic lipase and phospholipid transfer protein activities all decreased during high-protein feeding. Both high-CHO and high-PRO diets improve plasma lipid-related risk of cardiovascular disease when consumed ad libitum.