Vlc-pufa

The unique attributes of very long chain polyunsaturated fatty acids (VLC-PUFAs), their long carbon chains (n >24) and high degree of unsaturation, impart unique chemical and physical properties to this class of fatty acids. The changes imparted by VLC-PUFA 32:6 n-3 on lipid packing and the compression moduli of model membranes were evaluated from π-A isotherms of VLC-PUFA in 1,2-distearoyl-sn-3-glycero-phosphocholine (DSPC) lipid monolayers. In order to compare the attractive or repulsive forces between VLC-PUFA and DSPC lipid monolayers, the measured mean molecular areas (MMAs) were compared to the calculated MMAs of an ideal mixture of VLC-PUFA and DSPC...

Very long-chain (> C24) polyunsaturated fatty acids (VLC-PUFA) play an important role in the development of nervous system, retinal function and reproductive processes in vertebrates. Their presence in very small amounts in specific lipid classes, the lack of reference standards and their late elution in chromatographic analyses render their identification and, most important, their quantification, still a challenge. Consequently, a sensitive and feasible analytical methodology is needed. In this work, we have studied the effect of chain length, as well as the number and position of unsaturations (or double bonds) on the response of GC-APCI-(Q)TOF MS, to establish an analytical method for VLC-PUFA quantification...

PURPOSE: Very long-chain polyunsaturated fatty acids (VLC-PUFAs) are a distinct class of lipids with chain lengths greater than 24 carbons. ELOVL4 is a protein responsible for VLC-PUFA biosynthesis. However, in patients with autosomal dominant Stargardt 3 disease, the gene encoding ELOVL4 is mutated, and as a result, a dysfunctional, truncated protein is produced instead. It is unclear whether the disease phenotype is caused by truncated protein aggregates, the absence of VLC-PUFAs, or a combination of these factors...

PURPOSE: In many retinal pathological conditions, rod and cone degeneration differs. For example, the early-onset maculopathy Stargardts disease type 1 (STGD1) is typified by loss of cones while rods are often less affected. We wanted to examine whether there exist intrinsic membrane differences between rods and cones that might explain such features. METHODS: Abca4 mRNA and protein levels were quantified in rod- and cone-enriched samples from wild-type and Nrl-/- mice retinas; rod- and cone-enriched outer segments (ROS and COS respectively) were prepared from pig retinas, and total lipids were analyzed by flame ionization, chromatography, and tandem mass spectrometry...

Three new very long chain polyunsaturated fatty acids (VLC PUFA) belonging to the omega-3 family have been identified in meibum samples collected by Schirmer strips. These VLC PUFA, namely FA (32:3), FA (34:3) and FA (36:3), were detected in O-acyl-ω-hydroxy fatty acids using a molecular network approach, and as free fatty acids. Identification was supported by retention time prediction model, exact mass determination and isotopic patterns. Double bond location was determined using cross metathesis reaction associated to tandem mass spectrometry...

Cryopreservation is known to affect spermatozoa structure and function. Ram sperm are among the most highly sensitive mammalian gametes to freezing, due to their lipid composition, which limit their efficiency in artificial insemination programs. The aim of this study was to investigate the effects of cryopreservation with a chemically defined soybean lecithin-based extender on ram spermatozoa functionality on the one hand, and quantifiable changes in lipid and fatty acid profile on the other. Freeze-thawing decreased sperm quality, as indicated by post-thaw parameters related to membrane integrity, mitochondrial viability and sperm motility...

To contribute to further understanding the cellular and molecular complexities of inflammatory-immune responses in allergic disorders, we have tested the pro-homeostatic elovanoids (ELV) in human nasal epithelial cells (HNEpC) in culture challenged by several allergens. ELV are novel bioactive lipid mediators synthesized from the omega-3 very-long-chain polyunsaturated fatty acids (VLC-PUFA,n-3). We ask if: (a) several critical signaling events that sustain the integrity of the human nasal epithelium and other organ barriers are perturbed by house dust mites (HDM) and other allergens, and (b) if ELV would participate in beneficially modulating these events...

Retinal degeneration is a common feature in peroxisomal disorders leading to blindness. Peroxisomes are present in the different cell types of the retina; however, their precise contribution to retinal integrity is still unclear. We previously showed that mice lacking the central peroxisomal β-oxidation enzyme, multifunctional protein 2 (MFP2), develop an early onset retinal decay including photoreceptor cell death. To decipher the function of peroxisomal β-oxidation in photoreceptors, we generated cell type selective Mfp2 knockout mice, using the Crx promotor targeting photoreceptors and bipolar cells...

The search of the Phaeodactylum tricornutum genome database revealed the existence of six genes potentially encoding lysophospholipid acyltransferases. One of these genes, Phatr3_J20460, after introduction to yeast ale1 mutant disrupted in the LPCAT gene, produced a very active acyl-CoA:lysophosphatidylcholine (LPCAT) enzyme. Using in vitro assays applying different radioactive and non-radioactive substrates and microsomal fractions from such yeast, we have characterized the biochemical properties and substrate specificities of this Pt LPCAT1...

Nannochloropsis oceanica represents a promising sunlight-driven alga for producing eicosapentaenoic acid (EPA, 20:5Δ5 ,8,11,14,17 ), a value-added very long-chain polyunsaturated fatty acid (VLC-PUFA). Here, we unraveled the function and roles of a Δ6 fatty acid elongase (NoΔ6-FAE) in N. oceanica . Heterologous expression of NoΔ6-FAE in yeast confirmed its function in elongating C18 Δ6-PUFAs rather than others. Subcellular localization experiments suggested that NoΔ6-FAE resides in the chloroplast endoplasmic reticulum...

Spinocerebellar ataxia (SCA) is a neurodegenerative disorder characterized by ataxia and cerebellar atrophy. A number of different mutations gives rise to different types of SCA with characteristic ages of onset, symptomatology, and rates of progression. SCA type 34 (SCA34) is caused by mutations in ELOVL4 (ELOngation of Very Long-chain fatty acids 4), a fatty acid elongase essential for biosynthesis of Very Long Chain Saturated and Polyunsaturated Fatty Acids (VLC-SFA and VLC-PUFA, resp., ≥28 carbons), which have important functions in the brain, skin, retina, Meibomian glands, testes, and sperm...

Photoreceptors rely on distinct membrane compartments to support their specialized function. Unlike protein localization, identification of critical differences in membrane content has not yet been expanded to lipids, due to the difficulty of isolating domain-specific samples. We have overcome this by using SMA to coimmunopurify membrane proteins and their native lipids from two regions of photoreceptor ROS disks. Each sample's copurified lipids were subjected to untargeted lipidomic and fatty acid analysis...

The pro-homeostatic lipid mediators elovanoids (ELVs) attenuate cell binding and entrance of the SARS-CoV-2 receptor-binding domain (RBD) as well as of the SARS-CoV-2 virus in human primary alveoli cells in culture. We uncovered that very-long-chain polyunsaturated fatty acid precursors (VLC-PUFA, n-3) activate ELV biosynthesis in lung cells. Both ELVs and their precursors reduce the binding to RBD. ELVs downregulate angiotensin-converting enzyme 2 (ACE2) and enhance the expression of a set of protective proteins hindering cell surface virus binding and upregulating defensive proteins against lung damage...

This article describes the synthesis of VLC-PUFA 32:6 n-3, D2-labeled 32:6 n-3, and the uptake of 32:6 n-3 into mouse retinal tissue.

In Zellweger syndrome (ZS), lack of peroxisome function causes physiological and developmental abnormalities in many organs such as the brain, liver, muscles, and kidneys, but little is known about the exact pathogenic mechanism. By disrupting the zebrafish pex2 gene, we established a disease model for ZS and found that it exhibits pathological features and metabolic changes similar to those observed in human patients. By comprehensive analysis of the fatty acid profile, we found organ-specific accumulation and reduction of distinct fatty acid species, such as an accumulation of ultra-very-long-chain polyunsaturated fatty acids (ultra-VLC-PUFAs) in the brains of pex2 mutant fish...

The Heterokonta or Stramenopile phylum comprises clades of unicellular photosynthetic species, which are promising for a broad range of biotechnological applications, based on their capacity to capture atmospheric CO2 via photosynthesis and produce biomolecules of interest. These molecules include triacylglycerol (TAG) loaded inside specific cytosolic bodies, called the lipid droplets (LDs). Understanding TAG production and LD biogenesis and function in photosynthetic stramenopiles is therefore essential, and is mostly based on the study of a few emerging models, such as the pennate diatom Phaeodactylum tricornutum and eustigmatophytes, such as Nannochloropsis and Microchloropsis species...

Alteration of fatty-acid unsaturation is a universal response to temperature changes. Marine microalgae display the largest diversity of polyunsaturated fatty-acid (PUFA) whose content notably varies according to temperature. The physiological relevance and the molecular mechanisms underlying these changes are however, still poorly understood. The ancestral green picoalga Ostreococcus tauri displays original lipidic features that combines PUFAs from two distinctive microalgal lineages (Chlorophyceae, Chromista kingdom)...

There is limited knowledge about the metabolism and function of n-3 very-long-chain PUFA (n-3 VLC-PUFA) with chain lengths ≥ 24. They are known to be produced endogenously in certain tissues from EPA and DHA and not considered to originate directly from dietary sources. The aim of this study was to investigate whether n-3 VLC-PUFA from dietary sources are bio-available and deposited in tissues of rat, fish and mouse. Rats were fed diets supplemented with a natural fish oil (FO) as a source of low dietary levels of n-3 VLC-PUFA, while Atlantic salmon and mice were fed higher dietary levels of n-3 VLC-PUFA from a FO concentrate...

The essential fatty acid DHA (22:6, omega-3 or n-3) is enriched in and required for the membrane biogenesis and function of photoreceptor cells (PRCs), synapses, mitochondria, etc. of the CNS. PRC DHA becomes an acyl chain at the sn-2 of phosphatidylcholine, amounting to more than 50% of the PRC outer segment phospholipids, where phototransduction takes place. Very long chain PUFAs (n-3, ≥ 28 carbons) are at the sn-1 of this phosphatidylcholine molecular species and interact with rhodopsin. PRC shed their tips (DHA-rich membrane disks) daily, which in turn are phagocytized by the retinal pigment epithelium (RPE), where DHA is recycled back to PRC inner segments to be used for the biogenesis of new photoreceptor membranes...

Lipids play essential roles in maintaining cell structure and function by modulating membrane fluidity and cell signaling. The fatty acid elongase-4 (ELOVL4) protein, expressed in retina, brain, Meibomian glands, skin, testes and sperm, is an essential enzyme that mediates tissue-specific biosynthesis of both VLC-PUFA and VLC-saturated fatty acids (VLC-SFA). These fatty acids play critical roles in maintaining retina and brain function, neuroprotection, skin permeability barrier maintenance, and sperm function, among other important cellular processes...