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Special Issue "Bioactive Lipids and Lipidomics"

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (20 March 2015)

Special Issue Editors

Guest Editor
Prof. Dr. Mario Ollero

Université Paris Est Créteil, INSERM, U955, Créteil, France
Interests: lipidomics; proteomics; nephrology; immunology; nephrotic syndrome; membrane microdomains; membrane dynamics; lipid signaling
Guest Editor
Prof. Dr. Giuseppe Astarita (Website)

Georgetown University, Washington, DC, USA
Interests: lipidomics metabolomics nutrition

Special Issue Information

Dear Colleagues,

Recent advances in technologies for lipid analysis have contributed to the consolidation of lipidomics as a distinct discipline in molecular science. This technological development has paralleled the discovery of a broad range of cellular functions associated with lipids, from cell signaling and membrane dynamics, to intercellular communication and the regulation of gene expression. Lipid molecules have been identified as therapeutic targets, nutraceuticals and disease biomarkers.

The scope of this special issue is to cover the progress in Lipid Science & Technology, with regard to the state-of-the-art research in bioactive lipids and lipidomics.

Authors are invited to submit original research and review articles. Topics include, but are not limited to:

  • Bioactive lipids in cell biology
  • Lipid molecules as therapeutic agents and nutraceuticals
  • Lipids as diagnostic and prognostic biomarkers of disease
  • New advances in lipid analysis and lipidomics
  • Lipids in systems biology and metabolic networks

Prof. Dr. Mario Ollero
Prof. Dr. Giuseppe Astarita
Guest Editors

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs).

Keywords

  • metabolomics
  • systems biology
  • nutraceuticals
  • biomarkers
  • lipid signaling
  • lipid ligands

Published Papers (15 papers)

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Editorial

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Open AccessEditorial Lipidomics: An Evolving Discipline in Molecular Sciences
Int. J. Mol. Sci. 2015, 16(4), 7748-7752; doi:10.3390/ijms16047748
Received: 20 March 2015 / Revised: 20 March 2015 / Accepted: 30 March 2015 / Published: 8 April 2015
Cited by 2 | PDF Full-text (608 KB) | HTML Full-text | XML Full-text
Abstract Recent advances in technologies for lipid analysis have contributed to the consolidation of lipidomics as a distinct discipline in molecular sciences [1–6]. [...] Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)

Research

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Open AccessArticle A Simple and Effective Mass Spectrometric Approach to Identify the Adulteration of the Mediterranean Diet Component Extra-Virgin Olive Oil with Corn Oil
Int. J. Mol. Sci. 2015, 16(9), 20896-20912; doi:10.3390/ijms160920896
Received: 13 May 2015 / Revised: 29 July 2015 / Accepted: 18 August 2015 / Published: 1 September 2015
Cited by 1 | PDF Full-text (1691 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Extra virgin olive oil (EVOO) with its nutraceutical characteristics substantially contributes as a major nutrient to the health benefit of the Mediterranean diet. Unfortunately, the adulteration of EVOO with less expensive oils (e.g., peanut and corn oils), has become one of the [...] Read more.
Extra virgin olive oil (EVOO) with its nutraceutical characteristics substantially contributes as a major nutrient to the health benefit of the Mediterranean diet. Unfortunately, the adulteration of EVOO with less expensive oils (e.g., peanut and corn oils), has become one of the biggest source of agricultural fraud in the European Union, with important health implications for consumers, mainly due to the introduction of seed oil-derived allergens causing, especially in children, severe food allergy phenomena. In this regard, revealing adulterations of EVOO is of fundamental importance for health care and prevention reasons, especially in children. To this aim, effective analytical methods to assess EVOO purity are necessary. Here, we propose a simple, rapid, robust and very sensitive method for non-specialized mass spectrometric laboratory, based on the matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS) coupled to unsupervised hierarchical clustering (UHC), principal component (PCA) and Pearson’s correlation analyses, to reveal corn oil (CO) adulterations in EVOO at very low levels (down to 0.5%). Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)
Open AccessArticle Untargeted Metabolomics Reveals Predominant Alterations in Lipid Metabolism Following Light Exposure in Broccoli Sprouts
Int. J. Mol. Sci. 2015, 16(6), 13678-13691; doi:10.3390/ijms160613678
Received: 4 March 2015 / Accepted: 9 June 2015 / Published: 15 June 2015
Cited by 4 | PDF Full-text (1951 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The consumption of vegetables belonging to the family Brassicaceae (e.g., broccoli and cauliflower) is linked to a reduced incidence of cancer and cardiovascular diseases. The molecular composition of such plants is strongly affected by growing conditions. Here we developed an unbiased metabolomics [...] Read more.
The consumption of vegetables belonging to the family Brassicaceae (e.g., broccoli and cauliflower) is linked to a reduced incidence of cancer and cardiovascular diseases. The molecular composition of such plants is strongly affected by growing conditions. Here we developed an unbiased metabolomics approach to investigate the effect of light and dark exposure on the metabolome of broccoli sprouts and we applied such an approach to provide a bird’s-eye view of the overall metabolic response after light exposure. Broccoli seeds were germinated and grown hydroponically for five days in total darkness or with a light/dark photoperiod (16 h light/8 h dark cycle). We used an ultra-performance liquid-chromatography system coupled to an ion-mobility, time-of-flight mass spectrometer to profile the large array of metabolites present in the sprouts. Differences at the metabolite level between groups were analyzed using multivariate statistical analyses, including principal component analysis and correlation analysis. Altered metabolites were identified by searching publicly available and in-house databases. Metabolite pathway analyses were used to support the identification of subtle but significant changes among groups of related metabolites that may have gone unnoticed with conventional approaches. Besides the chlorophyll pathway, light exposure activated the biosynthesis and metabolism of sterol lipids, prenol lipids, and polyunsaturated lipids, which are essential for the photosynthetic machinery. Our results also revealed that light exposure increased the levels of polyketides, including flavonoids, and oxylipins, which play essential roles in the plant’s developmental processes and defense mechanism against herbivores. This study highlights the significant contribution of light exposure to the ultimate metabolic phenotype, which might affect the cellular physiology and nutritional value of broccoli sprouts. Furthermore, this study highlights the potential of an unbiased omics approach for the comprehensive study of the metabolism. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)
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Open AccessArticle Autistic Children Exhibit Decreased Levels of Essential Fatty Acids in Red Blood Cells
Int. J. Mol. Sci. 2015, 16(5), 10061-10076; doi:10.3390/ijms160510061
Received: 27 February 2015 / Revised: 19 April 2015 / Accepted: 29 April 2015 / Published: 4 May 2015
Cited by 11 | PDF Full-text (1030 KB) | HTML Full-text | XML Full-text
Abstract
Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) are essential nutrients for brain development and function. However, whether or not the levels of these fatty acids are altered in individuals with autism remains debatable. In this study, we compared the fatty [...] Read more.
Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) are essential nutrients for brain development and function. However, whether or not the levels of these fatty acids are altered in individuals with autism remains debatable. In this study, we compared the fatty acid contents between 121 autistic patients and 110 non-autistic, non-developmentally delayed controls, aged 3–17. Analysis of the fatty acid composition of red blood cell (RBC) membrane phospholipids showed that the percentage of total PUFA was lower in autistic patients than in controls; levels of n-6 arachidonic acid (AA) and n-3 docosahexaenoic acid (DHA) were particularly decreased (p < 0.001). In addition, plasma levels of the pro-inflammatory AA metabolite prostaglandin E2 (PGE2) were higher in a subset of the autistic participants (n = 20) compared to controls. Our study demonstrates an alteration in the PUFA profile and increased production of a PUFA-derived metabolite in autistic patients, supporting the hypothesis that abnormal lipid metabolism is implicated in autism. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)
Open AccessArticle Lipidome of Atherosclerotic Plaques from Hypercholesterolemic Rabbits
Int. J. Mol. Sci. 2014, 15(12), 23283-23293; doi:10.3390/ijms151223283
Received: 23 October 2014 / Revised: 9 December 2014 / Accepted: 10 December 2014 / Published: 15 December 2014
Cited by 3 | PDF Full-text (1907 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The cellular, macromolecular and neutral lipid composition of the atherosclerotic plaque has been extensively characterized. However, a comprehensive lipidomic analysis of the major lipid classes within atherosclerotic lesions has not been reported. The objective of this study was to produce a detailed [...] Read more.
The cellular, macromolecular and neutral lipid composition of the atherosclerotic plaque has been extensively characterized. However, a comprehensive lipidomic analysis of the major lipid classes within atherosclerotic lesions has not been reported. The objective of this study was to produce a detailed framework of the lipids that comprise the atherosclerotic lesion of a widely used pre-clinical model of plaque progression. Male New Zealand White rabbits were administered regular chow supplemented with 0.5% cholesterol (HC) for 12 weeks to induce hypercholesterolemia and atherosclerosis. Our lipidomic analyses of plaques isolated from rabbits fed the HC diet, using ultra-performance liquid chromatography (UPLC) and high-resolution mass spectrometry, detected most of the major lipid classes including: Cholesteryl esters, triacylglycerols, phosphatidylcholines, sphingomyelins, diacylglycerols, fatty acids, phosphatidylserines, lysophosphatidylcholines, ceramides, phosphatidylglycerols, phosphatidylinositols and phosphatidylethanolamines. Given that cholesteryl esters, triacylglycerols and phosphatidylcholines comprise greater than 75% of total plasma lipids, we directed particular attention towards the qualitative and quantitative assessment of the fatty acid composition of these lipids. We additionally found that sphingomyelins were relatively abundant lipid class within lesions, and compared the abundance of sphingomyelins to their precursor phosphatidylcholines. The studies presented here are the first approach to a comprehensive characterization of the atherosclerotic plaque lipidome. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)
Open AccessArticle Interactions of Borneol with DPPC Phospholipid Membranes: A Molecular Dynamics Simulation Study
Int. J. Mol. Sci. 2014, 15(11), 20365-20381; doi:10.3390/ijms151120365
Received: 15 August 2014 / Revised: 17 October 2014 / Accepted: 22 October 2014 / Published: 6 November 2014
Cited by 3 | PDF Full-text (1707 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Borneol, known as a “guide” drug in traditional Chinese medicine, is widely used as a natural penetration enhancer in modern clinical applications. Despite a large number of experimental studies on borneol’s penetration enhancing effect, the molecular basis of its action on bio-membranes [...] Read more.
Borneol, known as a “guide” drug in traditional Chinese medicine, is widely used as a natural penetration enhancer in modern clinical applications. Despite a large number of experimental studies on borneol’s penetration enhancing effect, the molecular basis of its action on bio-membranes is still unclear. We carried out a series of coarse-grained molecular dynamics simulations with the borneol concentration ranging from 3.31% to 54.59% (v/v, lipid-free basis) to study the interactions of borneol with aDPPC(1,2-dipalmitoylsn-glycero-3-phosphatidylcholine) bilayer membrane, and the temperature effects were also considered. At concentrations below 21.89%, borneol’s presence only caused DPPC bilayer thinning and an increase in fluidity; A rise in temperature could promote the diffusing progress of borneol. When the concentration was 21.89% or above, inverted micelle-like structures were formed within the bilayer interior, which led to increased bilayer thickness, and an optimum temperature was found for the interaction of borneol with the DPPC bilayer membrane. These findings revealed that the choice of optimal concentration and temperature is critical for a given application in which borneol is used as a penetration enhancer. Our results not only clarify some molecular basis for borneol’s penetration enhancing effects, but also provide some guidance for the development and applications of new preparations containing borneol. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)
Open AccessArticle Nuclear Lipid Microdomain as Resting Place of Dexamethasone to Impair Cell Proliferation
Int. J. Mol. Sci. 2014, 15(11), 19832-19846; doi:10.3390/ijms151119832
Received: 13 September 2014 / Revised: 24 October 2014 / Accepted: 27 October 2014 / Published: 31 October 2014
Cited by 3 | PDF Full-text (1571 KB) | HTML Full-text | XML Full-text
Abstract
The action of dexamethasone is initiated by, and strictly dependent upon, the interaction of the drug with its receptor followed by its translocation into the nucleus where modulates gene expression. Where the drug localizes at the intranuclear level is not yet known. [...] Read more.
The action of dexamethasone is initiated by, and strictly dependent upon, the interaction of the drug with its receptor followed by its translocation into the nucleus where modulates gene expression. Where the drug localizes at the intranuclear level is not yet known. We aimed to study the localization of the drug in nuclear lipid microdomains rich in sphingomyelin content that anchor active chromatin and act as platform for transcription modulation. The study was performed in non-Hodgkin’s T cell human lymphoblastic lymphoma (SUP-T1 cell line). We found that when dexamethasone enters into the nucleus it localizes in nuclear lipid microdomains where influences sphingomyelin metabolism. This is followed after 24 h by a cell cycle block accompanied by the up-regulation of cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin-dependent kinase inhibitor 1B (CDKN1B), growth arrest and DNA-damage 45A (GADD45A), and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) genes and by the reduction of signal transducer and activator of transcription 3 (STAT3) and phospho signal transducer and activator of transcription 3 (phoshoSTAT3) proteins. After 48 h some cells show morphological changes characteristic of apoptosis while the number of the cells that undergo cell division and express B-cell lymphoma-2 (Bcl-2) is very low. We suggest that the integrity of nuclear lipid microdomains is important for the response to glucocorticoids of cancer cells. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)
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Open AccessArticle FT-IR Microspectrometry Reveals the Variation of Membrane Polarizability due to Epigenomic Effect on Epithelial Ovarian Cancer
Int. J. Mol. Sci. 2014, 15(10), 17963-17973; doi:10.3390/ijms151017963
Received: 11 June 2014 / Revised: 8 September 2014 / Accepted: 23 September 2014 / Published: 8 October 2014
Cited by 2 | PDF Full-text (1453 KB) | HTML Full-text | XML Full-text
Abstract
Ovarian cancer, as well as other cancers, is primarily caused by methylation at cytosines in CpG islands, but the current marker for ovarian cancer is low in sensitivity and failed in early-stage detection. Fourier transform infrared (FT-IR) spectroscopy is powerful in analysis [...] Read more.
Ovarian cancer, as well as other cancers, is primarily caused by methylation at cytosines in CpG islands, but the current marker for ovarian cancer is low in sensitivity and failed in early-stage detection. Fourier transform infrared (FT-IR) spectroscopy is powerful in analysis of functional groups within molecules, and infrared microscopy illustrates the location of specific groups within single cells. In this study, we applied HPLC and FT-IR microspectrometry to study normal epithelial ovarian cell line immortalized ovarian surface epithelium (IOSE), two epithelial ovarian cell lines (A2780 and CP70) with distinct properties, and the effect of a cancer drug 5-aza-2'-deoxycytidine (5-aza) without labeling. Our results reveal that inhibition of methylation on cytosine with 5-aza initiates the protein expression. Furthermore, paraffin-adsorption kinetic study allows us to distinguish hypermethylated and hypomethyated cells, and this assay can be a potential diagnosis method for cancer screening. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)
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Open AccessArticle Impact of Inhaled Nitric Oxide on the Sulfatide Profile of Neonatal Rat Brain Studied by TOF-SIMS Imaging
Int. J. Mol. Sci. 2014, 15(4), 5233-5245; doi:10.3390/ijms15045233
Received: 15 January 2014 / Revised: 12 March 2014 / Accepted: 18 March 2014 / Published: 25 March 2014
Cited by 3 | PDF Full-text (1114 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Despite advances in neonatal intensive care leading to an increased survival rate in preterm infants, brain lesions and subsequent neurological handicaps following preterm birth remain a critical issue. To prevent brain injury and/or enhance repair, one of the most promising therapies investigated [...] Read more.
Despite advances in neonatal intensive care leading to an increased survival rate in preterm infants, brain lesions and subsequent neurological handicaps following preterm birth remain a critical issue. To prevent brain injury and/or enhance repair, one of the most promising therapies investigated in preclinical models is inhaled nitric oxide (iNO). We have assessed the effect of this therapy on brain lipid content in air- and iNO-exposed rat pups by mass spectrometry imaging using a time-of-flight secondary ion mass spectrometry (TOF-SIMS) method. This technique was used to map the variations in lipid composition of the rat brain and, particularly, of the white matter. Triplicate analysis showed a significant increase of sulfatides (25%–50%) in the white matter on Day 10 of life in iNO-exposed animals from Day 0–7 of life. These robust, repeatable and semi-quantitative data demonstrate a potent effect of iNO at the molecular level. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)
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Open AccessArticle Synergistic Enhancement of Cancer Therapy Using a Combination of Ceramide and Docetaxel
Int. J. Mol. Sci. 2014, 15(3), 4201-4220; doi:10.3390/ijms15034201
Received: 23 January 2014 / Revised: 19 February 2014 / Accepted: 21 February 2014 / Published: 10 March 2014
Cited by 6 | PDF Full-text (6976 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Ceramide (CE)-based combination therapy (CE combination) as a novel therapeutic strategy has attracted great attention in the field of anti-cancer therapy. The principal purposes of this study were to investigate the synergistic effect of CE in combination with docetaxel (DTX) (CE + [...] Read more.
Ceramide (CE)-based combination therapy (CE combination) as a novel therapeutic strategy has attracted great attention in the field of anti-cancer therapy. The principal purposes of this study were to investigate the synergistic effect of CE in combination with docetaxel (DTX) (CE + DTX) and to explore the synergy mechanisms of CE + DTX. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and combination index (CI) assay showed that simultaneous administration of CE and DTX with a molar ratio of 0.5:1 could generate the optimal synergistic effect on murine malignant melanoma cell (B16, CI = 0.31) and human breast carcinoma cell (MCF-7, CI = 0.48). The apoptosis, cell cycle, and cytoskeleton destruction study demonstrated that CE could target and destruct the microfilament actin, subsequently activate Caspase-3 and induce apoptosis. Meanwhile, DTX could target and disrupt the microtubules cytoskeleton, leading to a high proportion of cancer cells in G2/M-phase arrest. Moreover, CE plus DTX could cause a synergistic destruction of cytoskeleton, which resulted in a significantly higher apoptosis and a significantly higher arrest in G2/M arrest comparing with either agent alone (p < 0.01). The in vivo antitumor study evaluated in B16 tumor-bearing mice also validated the synergistic effects. All these results suggested that CE could enhance the antitumor activity of DTX in a synergistic manner, which suggest promising application prospects of CE + DTX combination treatment. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)
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Review

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Open AccessReview Lipidomics by Supercritical Fluid Chromatography
Int. J. Mol. Sci. 2015, 16(6), 13868-13884; doi:10.3390/ijms160613868
Received: 20 March 2015 / Revised: 12 May 2015 / Accepted: 28 May 2015 / Published: 17 June 2015
Cited by 5 | PDF Full-text (2138 KB) | HTML Full-text | XML Full-text
Abstract
This review enlightens the role of supercritical fluid chromatography (SFC) in the field of lipid analysis. SFC has been popular in the late 1980s and 1990s before almost disappearing due to the commercial success of liquid chromatography (LC). It is only 20 [...] Read more.
This review enlightens the role of supercritical fluid chromatography (SFC) in the field of lipid analysis. SFC has been popular in the late 1980s and 1990s before almost disappearing due to the commercial success of liquid chromatography (LC). It is only 20 years later that a regain of interest appeared when new commercial instruments were introduced. As SFC is fully compatible with the injection of extracts in pure organic solvent, this technique is perfectly suitable for lipid analysis and can be coupled with either highly universal (UV or evaporative light scattering) or highly specific (mass spectrometry) detection methods. A short history of the use of supercritical fluids as mobile phase for the separation oflipids will be introduced first. Then, the advantages and drawbacks of SFC are discussed for each class of lipids (fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterols, prenols, polyketides) defined by the LIPID MAPS consortium. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)
Open AccessReview Mechanisms Underlying the Anti-Aging and Anti-Tumor Effects of Lithocholic Bile Acid
Int. J. Mol. Sci. 2014, 15(9), 16522-16543; doi:10.3390/ijms150916522
Received: 24 July 2014 / Revised: 21 August 2014 / Accepted: 11 September 2014 / Published: 18 September 2014
Cited by 5 | PDF Full-text (1135 KB) | HTML Full-text | XML Full-text
Abstract
Bile acids are cholesterol-derived bioactive lipids that play essential roles in the maintenance of a heathy lifespan. These amphipathic molecules with detergent-like properties display numerous beneficial effects on various longevity- and healthspan-promoting processes in evolutionarily distant organisms. Recent studies revealed that lithocholic [...] Read more.
Bile acids are cholesterol-derived bioactive lipids that play essential roles in the maintenance of a heathy lifespan. These amphipathic molecules with detergent-like properties display numerous beneficial effects on various longevity- and healthspan-promoting processes in evolutionarily distant organisms. Recent studies revealed that lithocholic bile acid not only causes a considerable lifespan extension in yeast, but also exhibits a substantial cytotoxic effect in cultured cancer cells derived from different tissues and organisms. The molecular and cellular mechanisms underlying the robust anti-aging and anti-tumor effects of lithocholic acid have emerged. This review summarizes the current knowledge of these mechanisms, outlines the most important unanswered questions and suggests directions for future research. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)
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Open AccessReview Are Sensory TRP Channels Biological Alarms for Lipid Peroxidation?
Int. J. Mol. Sci. 2014, 15(9), 16430-16457; doi:10.3390/ijms150916430
Received: 6 July 2014 / Revised: 15 August 2014 / Accepted: 28 August 2014 / Published: 17 September 2014
Cited by 7 | PDF Full-text (1479 KB) | HTML Full-text | XML Full-text
Abstract
Oxidative stress induces numerous biological problems. Lipid oxidation and peroxidation appear to be important steps by which exposure to oxidative stress leads the body to a disease state. For its protection, the body has evolved to respond to and eliminate peroxidation products [...] Read more.
Oxidative stress induces numerous biological problems. Lipid oxidation and peroxidation appear to be important steps by which exposure to oxidative stress leads the body to a disease state. For its protection, the body has evolved to respond to and eliminate peroxidation products through the acquisition of binding proteins, reducing and conjugating enzymes, and excretion systems. During the past decade, researchers have identified a group of ion channel molecules that are activated by oxidized lipids: transient receptor potential (TRP) channels expressed in sensory neurons. These ion channels are fundamentally detectors and signal converters for body-damaging environments such as heat and cold temperatures, mechanical attacks, and potentially toxic substances. When messages initiated by TRP activation arrive at the brain, we perceive pain, which results in our preparing defensive responses. Excessive activation of the sensory neuronal TRP channels upon prolonged stimulations sometimes deteriorates the inflammatory state of damaged tissues by promoting neuropeptide release from expresser neurons. These same paradigms may also work for pathologic changes in the internal lipid environment upon exposure to oxidative stress. Here, we provide an overview of the role of TRP channels and oxidized lipid connections during abnormally increased oxidative signaling, and consider the sensory mechanism of TRP detection as an alert system. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)
Open AccessReview Abnormal Unsaturated Fatty Acid Metabolism in Cystic Fibrosis: Biochemical Mechanisms and Clinical Implications
Int. J. Mol. Sci. 2014, 15(9), 16083-16099; doi:10.3390/ijms150916083
Received: 20 June 2014 / Revised: 25 August 2014 / Accepted: 27 August 2014 / Published: 11 September 2014
Cited by 6 | PDF Full-text (739 KB) | HTML Full-text | XML Full-text
Abstract
Cystic fibrosis is an inherited multi-organ disorder caused by mutations in the CFTR gene. Patients with this disease exhibit characteristic abnormalities in the levels of unsaturated fatty acids in blood and tissue. Recent studies have uncovered an underlying biochemical mechanism for some [...] Read more.
Cystic fibrosis is an inherited multi-organ disorder caused by mutations in the CFTR gene. Patients with this disease exhibit characteristic abnormalities in the levels of unsaturated fatty acids in blood and tissue. Recent studies have uncovered an underlying biochemical mechanism for some of these changes, namely increased expression and activity of fatty acid desaturases. Among other effects, this drives metabolism of linoeate to arachidonate. Increased desaturase expression appears to be linked to cystic fibrosis mutations via stimulation of the AMP-activated protein kinase in the absence of functional CFTR protein. There is evidence that these abnormalities may contribute to disease pathophysiology by increasing production of eicosanoids, such as prostaglandins and leukotrienes, of which arachidonate is a key substrate. Understanding these underlying mechanisms provides key insights that could potentially impact the diagnosis, clinical monitoring, nutrition, and therapy of patients suffering from this deadly disease. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)
Open AccessReview Modified Low Density Lipoprotein and Lipoprotein-Containing Circulating Immune Complexes as Diagnostic and Prognostic Biomarkers of Atherosclerosis and Type 1 Diabetes Macrovascular Disease
Int. J. Mol. Sci. 2014, 15(7), 12807-12841; doi:10.3390/ijms150712807
Received: 11 May 2014 / Revised: 29 June 2014 / Accepted: 3 July 2014 / Published: 21 July 2014
Cited by 13 | PDF Full-text (1850 KB) | HTML Full-text | XML Full-text
Abstract
In atherosclerosis; blood low-density lipoproteins (LDL) are subjected to multiple enzymatic and non-enzymatic modifications that increase their atherogenicity and induce immunogenicity. Modified LDL are capable of inducing vascular inflammation through activation of innate immunity; thus, contributing to the progression of atherogenesis. The [...] Read more.
In atherosclerosis; blood low-density lipoproteins (LDL) are subjected to multiple enzymatic and non-enzymatic modifications that increase their atherogenicity and induce immunogenicity. Modified LDL are capable of inducing vascular inflammation through activation of innate immunity; thus, contributing to the progression of atherogenesis. The immunogenicity of modified LDL results in induction of self-antibodies specific to a certain type of modified LDL. The antibodies react with modified LDL forming circulating immune complexes. Circulating immune complexes exhibit prominent immunomodulatory properties that influence atherosclerotic inflammation. Compared to freely circulating modified LDL; modified LDL associated with the immune complexes have a more robust atherogenic and proinflammatory potential. Various lipid components of the immune complexes may serve not only as diagnostic but also as essential predictive markers of cardiovascular events in atherosclerosis. Accumulating evidence indicates that LDL-containing immune complexes can also serve as biomarker for macrovascular disease in type 1 diabetes. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)

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