Lipid Matters - Archive of Older Blogs - 2014

This Blog is an occasional series of notes on publications or other items dealing with lipid science that seem to be of particular interest to the editor Bill Christie. Inevitably, the selection is highly personal and subjective. In this web page, the blogs for 2014 are archived, while those for other years can be accessed from the foot of the current blog page.

December 24^th, 2014

Scottish thistle Lipid A is part of a complex lipopolysaccharide that is a distinctive component of the cell envelopes of Gram-negative bacteria, including those of human pathogens. They are of particular scientific interest in that they are toxins and stimulate strongly the innate immune system in eukaryotic host species. Lipid A provides the anchor that secures the molecule within the membrane, while a polysaccharide component interacts with the external environment. The key structural unit of interest to lipid chemists is an unusual disaccharide unit to which four fatty acids are attached, with up to three more linked via estolide bonds to the primary fatty acids. The number and nature of the fatty acids are correlated with the virulence of the organism. All very interesting I here you say, but why should we pay attention now?

Because of the increasing emergence of multidrug-resistant bacteria, there is a critical need for the development of novel antibiotics, and the detailed knowledge that has been gained of the biosynthetic pathway for lipid A is seen as providing a promising target for pharmaceutical intervention. Two substantial reviews on the chemistry and biochemistry of these fascinating compounds are now available online ahead of formal publication, and the first is open access (Wang, X. et al. Kdo2-lipid A: structural diversity and impact on immunopharmacology. Biol. Rev., in press (2015); DOI; - and Molinaro, A. et al. Chemistry of lipid A: at the heart of innate immunity. Chemistry - a European Journal, in press (2015); DOI).

Although the structure of lipid A is remarkably conserved across species, occasional surprises emerge, the latest of which is a form of lipid A with a hopanoid residue attached to one of the fatty acid constituents (Komaniecka, I. et al. Occurrence of an unusual hopanoid-containing Lipid A among lipopolysaccharides from Bradyrhizobium species. J. Biol. Chem., 289, 35644-35655 (2014); DOI).

A very merry Christmas and good health and happiness in the New Year to all my readers - I hope that you will look in again in January!

December 17^th, 2014

Amongst the tocopherols or more accurately the tocochromanols, plastochromanol-8 is something of a Cinderella molecule. In effect, it is an analogue of γ-tocotrienol with a longer side chain, but it is rarely mentioned in review articles other than simply as a footnote. On the other hand, it is now being reported from an increasing number of plant sources, mainly I suspect because analysts recognize that it may be present in lipid extracts and are looking for it. Its high molecular weight (750 versus 430 for α-tocopherol) means that it emerges from most chromatography systems at a very different time from other tocopherols so it is easily overlooked. It is probably not important as a food constituent for animals, but it is a rather powerful antioxidant in plants. While it is never as abundant as the tocopherols, its chemical and biological potency may make up for this. A new review will hopefully redress this neglect (Kruk, J. et al. Plastochromanol-8: fifty years of research. Phytochemistry, 108, 9-16 (2014); DOI).

A special issue of Biochimie (Vol. 107A, December 2014) is devoted the topic of "From Membranes to Pathologies" and is edited by Isabelle Mus-Veteau and Gérard Lambeau. There are four sections dealing with various aspects of lipid biochemistry and function, including one with the intriguing title "Lipids as sensors of smell, taste and sex". It is an obvious cliché, but I am tempted to say "only the French!"

December 10^th, 2014

Graphene is often represented as the new wonder material of the 21^st century and of course resulted in a Nobel prize for the discoverers. I didn't really expect it to appear in as an adjunct to lipid methodology, however. A new paper describes the use of solid-phase extraction method, employing a graphene and titanium dioxide nanocomposite as the sorbent for the selective isolation and enrichment of phospholipids. The method is based on the principal that the phosphoryl group in the phospholipid can interact with TiO₂ via a bridging bidentate mode to give highly selective separations. I am not sure what the graphene component does - perhaps simply acts as an inert substrate (Shen, Q. et al. Graphene/TiO₂ nanocomposite based solid-phase extraction and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for lipidomic profiling of avocado (Persea americana Mill.). Anal. Chim. Acta, 852, 153-161 (2014); DOI).

Phosphatidylserine is normally located on the internal leaflet of the plasma membrane, but on appropriate stimulation it is transferred to the outer leaflet where acts as a signal to passing macrophage that a cell has reached the end of its useful life and should be engulfed and degraded so that its constituents can be recycled. As a new review describes, it appears that viruses can hijack this machinery by incorporating this phospholipid into the viral envelopes. "Presentation of phosphatidylserine on the outer leaflet of these membranes disguises viruses as apoptotic bodies, thereby conning cells into engulfing virions through cell clearance mechanisms. This mechanism of enhanced virus entry is termed apoptotic mimicry" (Moller-Tank, S. and Maury, W. Phosphatidylserine receptors: Enhancers of enveloped virus entry and infection. Virology, 468, 565-580 (2014); DOI). The viral glycoprotein/cellular receptor complex may then facilitate the entry of viruses into other cells. Sneaky!

December 3^rd, 2014

I was never able to summon up much enthusiasm for the study of gangliosides, partly because they were more soluble in water than in most organic solvents and partly because they seemed to be of more interest to researchers in carbohydrates than in lipids. That view changed when I came across publications pointing out that one of the few and perhaps the only major biochemical difference between humans and the great apes was in the biosynthesis of the sialic acid constituents of gangliosides. As gangliosides are major components of brain lipids, it is easy to speculate on the importance of this fact. Two reviews have appeared on the chemistry/biochemistry of gangliosides, although I will have to be patient until the first is opened to non-subscribers (Schnaar, R.L. et al. Sialic acids in the brain: gangliosides and polysialic acid in nervous system development, stability, disease, and regeneration. Physiol. Rev., 94, 461-518 (2014); DOI: and Krengel, U. and Bousquet, P.A. Molecular recognition of gangliosides and their potential for cancer immunotherapies. Front. Immunol., 5, 325 (2014); DOI) At the more remote end of the animal spectrum, a marine mollusc lacks gangiosides entirely, but appears to replace them by complex oligoglycosylsphingolipids with phosphonyl- and phosphorylethanolamine residues instead of sialic acids (Satake, M. and Miyamoto, E. A group of glycosphingolipids found in an invertebrate: Their structures and biological significance. Proc. Jpn Acad. Ser. B, Phys. Biol. Sci., 88, 509-517 (2012); DOI). The last of these publications is two years old, but I had missed it earlier and it is open access (as is the previous one).

In my blog of two weeks ago, I mentioned a paper that cast doubt on the concept of lipid rafts, the microdomains in membranes enriched in cholesterol and sphingolipids that serve as signalling platforms. Now a new review deals with the more conventional view of rafts in some detail (Diaz-Rohrer, B. et al. Rafting through traffic: membrane domains in cellular logistics. Biochim. Biophys. Acta–Biomembranes, 1838, 3003-3013 (2014); DOI).

I have just discovered that a book entitled "Lipid Metabolism" and edited by Rodrigo Valenzuela Baez (472 pages, Publisher: InTech), and published in 2013 is available online and is fully open access (www.intechopen.com/books/lipid-metabolism). The choice of some of the subject matter appears a little eccentric, but there should be something for everyone. Chapters on the lipids of Mycobacteria and on the functions of jasmonates were of particular interest to me.

November 26^th, 2014

Scottish thistle The presence of arsenolipids in fish oils and in other marine organisms has been attracting great interest; more than 40 novel arsenolipid species have been found in the last two years alone. A piece of clever chemistry has just simplified the analytical problems. Extracts are reacted with hydrogen sulfide to convert oxo-arsenolipids to thio compounds to produce sharper peaks on chromatography with improvements in resolution and quantification by mass spectrometry (Glabonjat, R.A et al. Quantification of arsenolipids in the certified reference material NMIJ 7405-a (Hijiki) using HPLC/mass spectrometry after chemical derivatization. Anal. Chem., 86, 10282-10287 (2014); DOI). The paper is an authors' choice and therefore open access.

Those of us brought up in the Scottish school system received a very thorough grounding in the English language and react badly to poor usage. For example, I was taught to use the words "quantify and quantification" (as in the publication cited above) and never "quantitate and quantitation" and it grates when I see the latter in the title of a publication especially. On the other hand, I have to recognise that English is a highly dynamic language and is probably richer for it. I may have to acknowledge reluctantly that some usages have become so widespread that they may have to be accepted. However, I will go down fighting.

A special issue of the journal Cellular Physiology And Biochemistry (Vol. 34, No. 1, 2014) is devoted to the topic of "Biomedicine of Sphingolipids". The main emphasis is on sphingosine-1-phosphate, and happily all the articles are open access.

Google is rightly criticized in many quarters for reasons that are outwith the scope of this blog. However, the sheer convenience of using Google Scholar means that I use it more than any scientific website for a quick scan of the literature. Not only does it return the primary literature, but in many instances it returns copies of publications that may otherwise be embargoed in their manuscript form or from archives other than those of the publisher. Also I have found (probably belatedly) that by putting a DOI address into a Google query, it will take me straight to the publication without having to worry about the html syntax.

November 19^th, 2014

Triacylglycerol metabolism in adipose tissue is a major subject with vast implications for human health. It is worth standing back from this and examining the similar processes that occur in cytoplasmic lipid droplets in more primitive organisms. For example, there are many parallels with triacylglycerol metabolism in yeasts, which contain similar enzymes that are more amenable to study, as described in a new review (Koch, B. et al. Storage lipids of yeasts: a survey of nonpolar lipid metabolism in Saccharomyces cerevisiae, Pichia pastoris, and Yarrowia lipolytica. FEMS Microbiol. Rev., 38, 892-915 (2014); DOI). Microalgae also produce triacylglycerols but from a rather simple genome, with single isoforms of the main enzymes as opposed to the multiplicity in higher plants. They are of interest as model systems but also as potential commercial sources of biodiesel. Again, I can recommend a review that I have just encountered (Liu, B. and Benning, C. Lipid metabolism in microalgae distinguishes itself. Curr. Opinion Biotechnol., 24, 300-309 (2013); DOI).

The concept of lipid rafts, i.e., membrane domains enriched in sphingolipids and cholesterol that sequester specific proteins to serve as a signalling platform, seemed to me to be so well established that it was now standard text book fare. While I was updating the relevant web page on this site, it was therefore something of a surprise to come across a dissenting view (Kraft, M.L. Plasma membrane organization and function: moving past lipid rafts. Mol. Biol. Cell, 24, 2765-2768 (2013); DOI). The author suggests that most of the evidence for the existence of membrane rafts is indirect and proposes alternative explanations for the phenomena. I am happy to sit on the sidelines and leave the debate to others.

The journal Molecular Neurobiology (Volume 50, Issue 1, August 2014) is a special issue with the theme of "Unveiling the significance of lipid signaling in neurodegeneration and neuroprotection" (Issue Editors: Grace Sun and W. Gibson Wood). It looks interesting but I don't have access unfortunately.

November 12^th, 2014

I tend to think of cell membranes in terms of a common model that is depicted as a lipid bilayer with proteins inserted here and there. A new review presents a rather different perspective with proteins as the key components that shape membranes with lipids in a subsidiary role. I quote "While lipids may contribute and determine the plasticity of domain formation, it is proteins that hold the key to triggering such membrane re-organisation in an active and regulated manner". Some of the biochemistry is a bit specialized for me, but it was worthwhile to dip into the article (Rossy, J. et al. The organisation of the cell membrane: do proteins rule lipids? Curr. Opinion Chem. Biol., 20, 54-59 (2014); DOI).

When I do my regular literature searches, I tend to look for articles that deal with specific lipid classes to help me to revise my articles in the 'Lipid Essentials' section of this web site, but occasionally I come across new publications that are of great intrinsic interest but are not easy to classify in my simplistic terms. One such is a new review on how pathogenic bacteria hijack the lipid metabolism of their host for their own purposes (Vromman, F. and Subtil, A. Exploitation of host lipids by bacteria. Curr. Opinion Microbiol., 17, 38-45 (2014); DOI). Not only do bacteria use our lipids as a source of energy and for membrane constituents, but the host lipids are used to facilitate entry into cells and even to provide protective cocoons. At its worst, invading organisms such as Mycobacteria can "disturb host lipid metabolism so deeply as to 'reprogram' it". Some species can modify the lipids of the host, for example by taking up cholesterol, glycosylating it and then transferring the glycosylated lipid back to the host membrane, presumably for some nefarious reason.

November 5^th, 2014

The journal Nature has an on-line article on the 100 most cited publications of all time including a full listing. Top of the list, perhaps not surprisingly was the Lowry method for protein determination with over 300,000 citations. Four papers relevant to lipids are listed, all dealing with methodology. Ranked at number 9 is the Folch, Lees and Stanley procedure for lipid extractions from 1957 with 45,000 citations, while the comparable Bligh and Dyer method comes in at number 18 with 32,000 citations. Perhaps I am cynical but I wonder how many of those citing these papers have actually read them? Further down the list are methods for cholesterol (No. 62) and phosphorus determination (No. 81). The authors of the article point out that "The discovery of high-temperature superconductors, the determination of DNA’s double-helix structure, the first observations that the expansion of the Universe is accelerating — all of these breakthroughs won Nobel prizes and international acclaim. Yet none of the papers that announced them comes anywhere close to ranking among the 100 most highly cited papers of all time." In fact, it appears that a high proportion describe experimental methods that have become essential in their fields. Three cheers for lipid analysts!

The question of whether ether lipids are present in plants has been a controversial one with reports both for and against. However, there now appears to be a definitive report of the presence of galactolipids with an ether-linked 1-O-phytyl moiety in algae. The analytical procedure was sensitive but involved a partial hydrolysis step followed by derivatization, so we can only surmise that the intact lipid may have contained a fatty acid in position sn-2. The lipid was detected in green, red and brown marine algae, and in two of the higher plants examined (Ishibashi, Y. et al. A novel ether-linked phytol-containing digalactosylglycerolipid in the marine green alga, Ulva pertusa. Biochem. Biophys. Res. Commun., 452, 873-880 (2014); DOI).

October 29^th, 2014

Scottish thistle One of the things I like about the Journal of Lipid Research is that it allows free access to manuscripts of papers that have been accepted for publication but are still in press. I have especially enjoyed reading a new review in this format on how essential fatty acids were discovered by George and Mildred Burr (Spector, A.A. and Kim, H.-Y. Discovery of essential fatty acids. J. Lipid Res., in press; DOI). When they reported their discovery of the essentiality of linoleic acid in 1929, they had the greatest difficulty in persuading their colleagues in the University of Minnesota of the truth of their findings. I knew part of the story from the two years I spent in the laboratory of Ralph Holman, one of Burr's former students, but this is an especially comprehensive account. Incidentally, some of senior staff of the University of Minnesota appeared to be still unconvinced in the mid-60s. One commented to one of my colleagues that "working with lipids was like working on the biochemistry of coal" - the implication being that lipids were only of value as a source of energy!

An interesting paper (open access) on plant biochemistry reached my desk this week (Li, Y. et al. Acyl chain length of phosphatidylserine is correlated with plant lifespan. PLOS One, 9, e103227 (2014); DOI). It seems that the total chain-lengths of the fatty acids in phosphatidylserine increase as a plant ages. The authors hypothesize that the cell bilayers in plants have a limited tolerance for this phenomenon and die when a specific point is reached - "the average chain-length of PS could be a molecular scale ruler measuring plant lifespan".

October 22^nd, 2014

In my last blog, I highlighted the complexity of cow's milk fat as a test bed for triacylglycerol analysis by HPLC. It is also invaluable to test new methodology for the analysis of the complex mixture of minor fatty acid components. Some years ago with my colleague Elizabeth Brechany, I was able to identify more than 50 oxo (keto) fatty acids in cheese, half of which were new to science - see my revamped web pages on mass spectra of methyl esters and 3-pyridylcarbinol esters of these fatty acids. We never did come up with a convincing explanation of their biosynthetic origin. Walter Vetter and colleagues recently identified 430 different fatty acids from cow's milk using their countercurrent distribution methodology allied to GC-MS. They have just added a number of novel fatty acids with terminal phenyl groups to this list (Schröder, M. et al. Identification of aromatic fatty acids in butter fat. J. Am. Oil Chem. Soc., 91, 1695-1702 (2014); DOI). It seems that these may have been produced by the microbial population of the rumen.

The same issue of this journal contains an important paper in which the densities of various fatty acid derivatives were systematically determined and recorded. Such compilations of physical data from a single source may appear unspectacular but are an invaluable resource (Knothe, G. and Steidley, K.R. A comprehensive evaluation of the density of neat fatty acids and esters. J. Am. Oil Chem. Soc., 91, 1711-1722 (2014); DOI).

In higher plants, mono- and digalactosyldiacylglycerols are key components of the thylakoid membranes and are considered to be essential for photosynthesis. A new study demonstrates that this may not be true in cyanobacteria. When a key enzyme was knocked out, the mutant organisms could not produce galactolipids but glucosyldiacylglycerol instead. They were still able to photosynthesize normally, if a little less efficiently. (Awai, K. et al. Oxygenic photosynthesis without galactolipids. Proc. Natl. Acad. Sci., USA, 111, 13571-13575 (2014); DOI).

October 15^th, 2014

Recent publications from the laboratory of Professor B.A. Freeman provided additional evidence for the potential medical benefits of nitro fatty acids. First, a finding that nitro-oleate is present in olives and olive oil lead to the intriguing suggestion that this may be an element in the benefits to cardiovascular health associated with the Mediterranean diet (Fazzari, M. et al. Olives and olive oil are sources of electrophilic fatty acid nitroalkenes. PLOS One, 9, e84884 (2014); DOI). Evidence in favour of this hypothesis was subsequently published, suggesting that the effect might be mediated by inhibition of the enzyme responsible for the hydrolysis of epoxyeicosatrienoic acid, which has protective effects against hypertension (Charles, R.L. et al. Protection from hypertension in mice by the Mediterranean diet is mediated by nitro fatty acid inhibition of soluble epoxide hydrolase. Proc. Nat. Acad. Sci., USA, 111, 8167-8172 (2014); DOI). Finally, it is reported that nitro-oleate has beneficial affects against hypertension in obesity (Kelley, E.E. et al. Fatty acid nitroalkenes ameliorate glucose intolerance and pulmonary hypertension in high-fat diet-induced obesity. Cardiovasc. Res., 101, 352-363 (2014); DOI). I understand that preliminary clinical trials are proving encouraging.

I am not an expert on medical aspects of lipids, so I find it helpful when others do some of the interpreting for me. For example, two publications in the October issue of the Journal of Lipid Research show that synthetic peptides that mimic apoprotein A1 can be administered orally to improve the levels of cholesterol and reduce plaque buildup in the arteries of animal models. Science Daily News has discussed the findings with the authors of the reports and describes the findings in a manner appropriate to non-experts.

In the days when I was closer to the bench, I had an interest in reversed-phase HPLC of lipids and as part of my former background at a dairy research institute I had a specific interest in milk triacylglycerols. Such was their complexity, that they provided a challenge for any new development in chromatography. I was therefore interested in a new publication, which shows what can be achieved by ultra high performance liquid chromatography (Beccaria, M. et al. High performance characterization of triacylglycerols in milk and milk-related samples by liquid chromatography and mass spectrometry. J. Chromatogr. A, 1360, 172-187 (2014); DOI).

October 8^th, 2014

New lipid structures continue to be found in nature and I am grateful to a friend for passing a new publication from an ACS journal to me. This reports the characterization of two new lipids structures in the bacterium Bifidobacterium longum subs. infantis, which resides in the intestinal tract of infants. This contains a novel form of cyclic phosphatidic acid with a plasmenyl linkage, together with a galactofuranosyl-diacylglycerol with a novel acetal linkage to glycerol, which was found to suppress the innate immune response (Timmer, M.S.M. et al. Discovery of lipids from B. longum subsp infantis using whole cell MALDI analysis. J. Org. Chem., 79, 7332-7341 (2014); DOI).

Another lipid that was new to me, although perhaps I should have been aware of it earlier, is a 6-iodolactone of arachidonic acid (5-hydroxy-6-iodo-8,11,14-eicosatrienoic acid, δ-lactone). This can be formed by a simple chemical reaction of iodine with the double bond in position 5 of arachidonic acid, which readily forms delta-lactones, or it can be produced enzymatically. Arachidonic acid and iodine encounter each other in the thyroid gland and this unusual lipid has been detected in this tissue. Now a new publication reports that this compound has antiproliferative and apoptotic effects observed thyrocytes, and suggests that it may have beneficial effects against a variety of cancers if administered as a pharmaceutical supplement (Nava-Villalba, M. and Aceves, C. 6-Iodolactone, key mediator of antitumoral properties of iodine. Prostaglandins Other Lipid Mediators, 112, 27-33 (2014); DOI).

October 1^st, 2014

The new techniques of lipidomics have given us a greater awareness of the importance of individual molecular species in the functions of lipids. Phosphatidylcholine, for example, can occur naturally as a complex mixture of at least a hundred molecular species. Yet there can be an essential requirement for only one of these in some circumstances. A new publication demonstrates that 1-oleoyl-2-palmitoyl-phosphatidylcholine is located specifically at the protrusion tips of neuronal cells and appears to be essential for their function. It is noteworthy that the structure is distinctive in that we usually expect the saturated fatty acid in position sn-1 and the unsaturated in position sn-2. I was also pleased to see that the structure was determined by hydrolysis with the phospholipase of snake venom - a procedure that I feared might be forgotten by modern researchers (Kuge, H. et al. Functional compartmentalization of the plasma membrane of neurons by a unique acyl chain composition of phospholipids. J. Biol. Chem., 289, 26783-26793 (2014); DOI).

I am used to see publications on the analysis of a sole eicosanoid - prostaglandin "this" and eicosanoid "that". It was therefore a pleasing surprise to see a paper from the laboratory of Professor E.A. Dennis describing the analysis of 184 distinct eicosanoids in a single chromatographic run in only five minutes. The use of deuterated internal standards and tandem mass spectrometry ensures accurate quantification - a real tour de force (Wang, Y. et al. Comprehensive ultra-performance liquid chromatographic separation and mass spectrometric analysis of eicosanoid metabolites in human samples. J. Chromatogr. A, 1359, 60-69 (2014); DOI).

Two special issues of journals devoted to specific lipid topics have appeared - "Current Research, Knowledge and Controversies on High Density Lipoprotein" (edited by M. Banach, in Current Medicinal Chemistry, Volume 21, Number 25) and "Endocannabinoids and Nutrition" (edited by M. Maccarrone, BioFactors, Volume 40, Issue 4). I don't have access to either journal so I can't comment further.

September 24^th, 2014

Scottish thistle There is a special issue of Pharmacological Research (Volume 86, Pages 1-50 (August 2014)) on the topic of "Lipid amide signaling: regulation, physiological roles and pathological implications" (edited by Daniele Piomelli and Oscar Sasso). Rather than the story of the endocannabinoid anandamide, which is increasingly well known, these reviews deal with the other ethanolamides. For example, palmitoylethanolamide has anti-inflammatory and analgesic properties, while oleoylethanolamide and linoleoylethanolamide are considered to be an anorectic in that they reduce apetite. They appear to mediate their signalling activity by activating of PPARα in enterocytes. Ethanolamides also have a role in injury to the brain with palmitoylethanolamide especially being neuroprotective, and they are being studied in relation to nicotine addiction. Drugs that target the enzymes involved in their biosynthesis and catabolism are being sought. I expect that we will be hearing much more of these compounds in the future.

N-Acylethanolamides are also important as signalling compounds in plants, and they are the subject of a separate review that focuses on their functions, especially in relation to early seedling growth and development (Blancaflor, E.B. et al. N-Acylethanolamines: lipid metabolites with functions in plant growth and development. Plant J., 79, 568-583 (2014); DOI).

The journal Traffic (Volume 15, issue 9) contains a series of reviews with the theme of "Interorganelle Trafficking of Lipids" (edited by K. Hanada, and D. Voelker).

September 17^th, 2014

Two publications from the Proceedings of the National Academy of Sciences (USA) caught my eye this week. I have heard lipids called many things over the years, but never a ‘zipper’. However, this was the term used to describe how the oligoglycosphingolipid Gb3 or GbOse3Cer, an important component of human plasma membranes, interacts with lectins on the bacterial surface. This triggers bending of the plasma membrane during host cell invasion by the bacterium Pseudomonas aeruginosa, resulting in complete engulfment of the bacterium by the membrane (Eierhoff, T. et al. A lipid zipper triggers bacterial invasion. PNAS, 111, 12895-12900 (2014); DOI).

The second paper from the laboratory of E.A. Dennis deals with the action of phospholipase A₂ activity and with lipoxin formation. The phospholipase is believed to the first key step in the production of inflammatory prostaglandins, while lipoxins have the opposite effect of promoting the resolution of inflammation. In macrophages, it seems that phospholipase A₂ has a dual function in that it releases 15-hydroxyeicosatetraenoic acid (15-HETE) from its esterified form in membrane phospholipids to serve as the precursor for lipoxins. Thus, the enzyme assists both inflammatory and anti-inflammatory processes in the same cell. Another notable finding is that all the steps to lipoxin synthesis occur in the single cell type, in contrast to the established pathways which require the precursor to be passed from one cell to another (Norris, P.C. et al. Phospholipase A₂ regulates eicosanoid class switching during inflammasome activation. PNAS, 111, 12746-12751 (2014); DOI).

Incidentally, I like the policy of PNAS in that it asks the authors for a paragraph to discuss the significance of their work in terms suited to a general biochemistry audience, distinct from the abstract, which is intended for specialists.

September 10^th, 2014

N-Oleoylethanolamide is an endogenous regulator of food intake, which is under active investigation as an anti-obesity drug. No other fatty acyl ethanolamide will do. It is believed to act as a local satiety signal rather than as a blood-borne hormone. A new publication suggests that this lipid is an important factor that fuels the growth of cells in chronic lymphocytic leukemia and may be involved in drug resistance and the wasting effects of the disease. No doubt the search is on for drugs that might control its concentration in cells to alleviate the symptoms of this dreadful illness (Masoodi, M. et al. A role for oleoylethanolamide in chronic lymphocytic leukemia. Leukemia, 28, 1381-1387 (2014); DOI). Also, I am sure that the relevance of this lipid to other cancers will be under active investigation.

Two papers appeared in a recent issue of the British Journal of Pharmacology dealing with subjects that I felt was only of interest to the ultra-specialist and would be rather boring to the rest of us (i.e., Bäck, M. et al. Update on leukotriene, lipoxin and oxoeicosanoid receptors: IUPHAR Review 7. Brit. J. Pharm., 171, 3551-3574 (2014); DOI; and, Kihara, Y. et al. Lysophospholipid receptor nomenclature review: IUPHAR Review 8. Brit. J. Pharm., 171, 3575-3594 (2014) - DOI). I am glad that I had a closer look, as although they are not exactly light bed-time reading they do bring together much valuable information from disparate sources, illustrating relationships of which I was unaware. Both publications are open access.

September 3^rd, 2014

I had never taken much interest in bile acids until recently, as I found it hard to understand how such water-soluble compounds could even be considered as lipids. They dwelled in the murkier regions of the body with to me at least an equally murky metabolism. Now all is light. I suspect that a substantial new review on the topic may become a classic. It is part of a Thematic Review Series: Living History of Lipids (Hofmann, A.F. and Hagey, L.R. Key discoveries in bile acid chemistry and biology and their clinical applications: history of the last eight decades. J. Lipid Res., 55, 1553-1595 (2014); DOI). It is a fascinating and readable account from the very early days to the present.

Now it is recognised that not only do bile acids play a key role in the absorption, transport, and metabolism of dietary fats and lipid-soluble vitamins from the intestines and a route for the elimination of excess cholesterol, but they activate a number of nuclear receptors involved in the regulation of lipid, glucose and energy metabolism, for example. Two recent review highlight the latter aspects of bile acid metabolism (Li, T. and Chiang, J.Y.L. Bile acid signaling in metabolic disease and drug therapy. Pharmacol. Rev., 66, 948-983 (2014); DOI; and, Zhou, H. and Hylemon, P.B. Bile acids are nutrient signaling hormones. Steroids, 86, 62-68 (2014); DOI).

August 27^th, 2014

Scottish thistle One of the more important areas of discovery in relation to lipids in recent years has been the revelation that metabolites of the C₂₀ and C₂₂ omega-3 fatty acids, the resolvins, protectins and maresins or as we are encouraged to call them the termed ‘specialized pro-resolving mediators’ or SPMs are key anti-inflammatory molecules. Inflammation is an essential response to infection or injury, but it could be harmful if allowed to go unchecked – the SPMs provide that check. The biochemical importance of these lipids has been much of the focus of current research, but a detailed knowledge of their natural occurrence in tissues is important to establish base-line levels. This appears now to have been done (Colas, R.A. et al. Identification and signature profiles for pro-resolving and inflammatory lipid mediators in human tissue. Am. J. Physiol.-Cell Physiol., 307, C39-C54 (2014); DOI). I say ‘appears’ as I have to be patient until it becomes open access after 6 months. This is not a complaint as I am grateful for this enlightened policy to which few chemical journals subscribe unfortunately.

The Journal of Chromatography B, Volume 964, Pages 1-224 (2014) is a special issue with the theme of ‘Analysis of Eicosanoids, Amino Acids, Organic Acids and microRNA’ (edited by Dimitrios Tsikas and Alexander A. Zoerner), and has a number of articles of interest to lipid analysts.

August 20^th, 2014

The Journal of Biological Chemistry, Issue 33, contains five articles under the heading ‘Thematic Minireview Series on Phospholipase D and Cancer’ (edited by Julian Gomez-Cambronero and George M. Carman). I was familiar of course with the role of the product phosphatidic acid in many biological processes, but it was a surprise to learn that the enzyme per se participated in innumerable metabolic events via protein-protein interactions.

Note: For various personal reasons, there was a break in my blogs for several months in 2014.

April 9^th, 2014

Scottish thistle I have just read that a clause in the Nature Publishing Group’s license agreement states that authors waive or agree not to assert "any and all moral rights they may now or in the future hold" related to their work. This appears to include the right of the author always to have his/her name associated with a publication. It has the potential also to allow publications to be changed in a manner that might cause damage to the reputation of an author. In fact, it appears that the intention of this clause is to enable journals to publish corrections or retractions, against the wishes of the author if necessary, but surely the clause could have been worded more clearly.

The most unusual lipid paper to cross my path this week is - Khrameeva, E.E. et al. Neanderthal ancestry drives evolution of lipid catabolism in contemporary Europeans. Nature Commun., 5, 3584 (2014); DOI). It appears that contemporary humans of European descent have a greater than threefold excess of Neanderthal-like sites in those genes involved in lipid catabolism, in comparison to Asian or African populations. If you are interested, the paper is open access.

The glycosylglycerolipids such as mono- and digalactosyldiacylglycerols are vital molecules and one of the keys to life in that they are essential to the membranes involved in photosynthesis from cyanobacteria to chloroplasts of eukaryotic cells. Two new review articles (sharing key authors) discuss this from a similar perspective (Boudiere, L. et al. Glycerolipids in photosynthesis: Composition, synthesis and trafficking. Biochim. Biophys. Acta Bioenergetics, 1837, 470-480 (2014); DOI; Petroutsos, D. et al. Evolution of galactoglycerolipid biosynthetic pathways – From cyanobacteria to primary plastids and from primary to secondary plastids. Prog. Lipid Res., 54, 68-85 (2014); DOI). During phosphate deprivation, these lipids seem to be able to replace phospholipids in other plant membranes. For such reasons, I have argued that the Lipid Maps consortium should recognise glycosylglycerolipids in a similar hierarchy to phospholipids in their classification scheme, but so far to no avail.

The May issue of Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids Volume 1841, Issue 5, Pages 645-826 now online is devoted to “New Frontiers in Sphingolipid Biology” (edited by J. Holthuis and Y. Igarashi) and contains more than 20 original review articles on the topic. Lipids were unpopular as a subject for research in academia for many years, and sphingolipids especially were neglected. This has certainly been rectified, and sphingolipid research is now a major growth area. I noted in passing that in one chapter the authors “focus on finding ways of modulating sphingolipids to prevent the development of age-associated diseases or delay their onset, both of which could improve health in elderly, fragile people”. I am not fragile yet, but I do have my off days.

My other complaint is that I haven’t had time to catch up with the March special issue of this journal dealing with ceramides yet.

March, 2014

Scottish thistle We hear so much bad news about lipids or ‘fat’, that I am always intrigued by news of beneficial lipids and especially of applications as pharmaceuticals to fight disease. I was therefore intrigued by a new review on bacterial lipopeptides (Schneider, T. et al. Cyclic lipopeptides as antibacterial agents - potent antibiotic activity mediated by intriguing mode of actions. Int. J. Med. Microbiol., 304, 37-43 (2014); DOI). They can consist of short linear chains or cyclic structures of amino acids, linked to a fatty acid via ester or amide bonds or both. Often the amino acids are of the D- rather than the usual L-configuration, presumably to resist the action of proteases. The fatty acid constituents add to the variability, for example in chain-length (C₆-C₁₈) and often the presence of hydroxyl groups and/or iso- or anteiso-methyl branches. Many have surfactant, antibacterial or antifungal properties and have attracted interest from industry. For example, polymixins act by binding to the lipid A moiety of lipopolysaccharides, and they are used to treat a variety of infections caused by Gram-negative bacteria, especially in topical applications, such as wound creams and eye or ear drops. While they have been considered to be too toxic to be used as systemic antibiotics, they are now finding application against multi-drug-resistant Gram-negative bacilli. Synthetic variants of polymixins and other lipopeptides are now being developed with reduced toxicity and improved antibacterial properties.

The popular press has got hold of details of yet another major study which finds that there is no link between the intake of saturated fatty acids and cardiovascular health (www.bbc.co.uk/news/health-26611861). That “saturated fatty acids are bad” has been dogma amongst nutritionists for 50 years, and it seems to me that some response other than simply a shrug of the shoulders is required now. Why have two generations been persuaded to give up tasty natural foods such as butter and whole-fat milk when it was not necessary? The poisonous campaign against “tropical” fats promoted by the soybean industry should not be forgotten either. Of course, all of this depends on whether we can rely on the new findings.

One study to catch my eye this week was a comparison of the plasma lipids in centenarians versus those in other health in other elderly subjects (Montoliu, I. et al. Serum profiling of healthy aging identifies phospho- and sphingolipid species as markers of human longevity. Aging US, 6, 9-25 (2014) (www.impactaging.com/papers/v6/n1/abs/100630a.html)). It seems that there were important differences in the compositions of the phospho-and sphingolipids between the two. Now I have to work out how to change my own plasma lipid composition in the appropriate direction. My grandmother managed to reach her hundredth birthday, but I am not sure that it was worth the bother.

I have just been catching up on the back issues of the French journal Oleagineux, Corps gras, Lipides, which I had missed because I was unaware that it had changed its title to OCL - Oilseeds and fats, Crops and Lipids and its URL (www.ocl-journal.org). Many articles are in English and now it is fully open access, so it is worth a look.

A.T. (Tony) James was one of the great pioneers of lipid chemistry as one of the inventors of gas chromatography as well as its application to fatty acid analysis. However, his accomplishments as a scientist go far beyond this, and amongst other lipid-oriented topics he made important contributions to plant biochemistry and human nutrition. I have spend an enjoyable weekend reading a biography written my Mike Gurr (self published at £18, including p.&p. in the UK, contact email: manda.gurr@btinternet.com). It will be difficult for the modern generation to comprehend the poverty of James upbringing, but it is impossible not to admire how he pulled himself out of this mire after leaving school at 16 and developed into such an eminent scientist. Gurr worked with James for 10 years or so during some of the latter’s most productive years, so the book is full of anecdotes that point to the character of his subject. It is written with affection, but is critical when necessary. If James was lucky in many of his choices in life, he has also been fortunate in having Mike Gurr as his biographer.

In the last few weeks, I have seen newspaper headlines stating that dietary protein is as dangerous to health as smoking and that the sugar and carbohydrate content of the diet should be drastically reduced. Meanwhile, saturated fats are no longer considered harmful to health, and boosting levels of omega-3 fatty acids enables children to sleep longer and better. What should we believe? I like one reporter’s comment – “After decades of study, the best, most well-supported advice is still what your mother told you: eat your greens and get plenty of exercise”. My mother used to tell me that fish was brain food, so I am intrigued by a new report discussed in Bruce Holub’s DHA/EPA Omega-3 Institute that high DHA levels (but not EPA) are correlated with a reduction in cognitive decline in the elderly. As I like fish, I want to believe this. Perhaps this is part of the problem with nutritional advice in general, we can always find something in the scientific or popular press that supports our own dietary preferences.

Another lipid story to make headlines in our national newspapers is that a test has been found for Alzheimer's disease that can predict its occurrence three years before symptoms develop. It seems that the levels of ten lipid components in plasma, mainly molecular species of phosphatidylcholine and lysophosphatidylcholine, are good diagnostic markers. This looks like being simply a research tool for the immediate future, but hopefully earlier diagnosis will lead to improved treatments in the longer term as well as keeping lipid analysts gainfully employed. The details are in a paper from Howard Federoff's laboratory published in Nature Medicine.

A few weeks ago I made some critical comments on how '-omics' was being used (or abused) to coin a plethora of new words for lipid topics. To add to these we now have 'cardiolipinomics' in a special issue of Chemistry and Physics of Lipids (Volume 179, Pages 1-82 (April 2014)) "Progress in Cardiolipinomics" and edited by V.E. Kagan and R.M. Epand. Title aside, this looks like a fascinating compendium of review articles.

I have recently come across 'Wild Types', a blog for ASBMB Today, by Rajendrani Mukhopadhyay. Two recent posts deal with lipids - Figuring out the target for Lorenzo’s oil and Gut bacteria may be a source of male steroid hormones

The stratum corneum layer is unique in that it contains relatively high levels of ceramides (as much as 50% of the total lipids), including distinctive O-acylceramides found nowhere else. There is a special issue of Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids (Vol. 1841, Issue 3 pp. 279-474 (March 2014) dealing with “The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier” (edited by K.R. Feingold and P.M. Elias). There are more than 20 articles, a number of which are concerned with the biochemistry and function of these unique ceramides. By coincidence, there is a fascinating review on ceramides in Progress in Lipid Research (online only at the moment) (Castro, B.M. et al. Ceramide: A simple sphingolipid with unique biophysical properties. Prog. Lipid Res., 54, 53-67 (2014); DOI).

A new review poses an interesting question (Wang, H. and Eckel, R.H. What are lipoproteins doing in the brain? Trends Endocrinol. Metab., 25, 8-14 (2014); DOI). It appears that they are doing quite a lot. For example, I was unaware that HDL can cross the blood-brain barrier, though most are synthesised within the central nervous system including the most abundant apolipoproteins (Apo E and Apo J). Lipoproteins regulate neurological behaviour via specific receptors, and they take part in the regulation of body weight and energy balance.

February, 2014

Scottish thistle I have never liked the term ‘endocannabinoids’, which I presume means ‘cannabinoids within the body’. As a new review of the topic, which happily is open access, points out, it is the exogenous cannabinoids that have hijacked the brain’s neurotransmitter system involving anandamide and 2-arachidonoylglycerol - not the reverse (Piomelli, D. More surprises lying ahead. The endocannabinoids keep us guessing. Neuropharmacology, 76, 228-234 (2014); DOI). Perhaps we should rename ‘cannabinoids’ as ‘exoanandamides’. Joking aside, an interesting feature of the review is that it discusses what we don’t know about the subject as well as the latest findings. By coincidence I came across a quotation by Niels Bohr this week – “If you aren’t confused by quantum physics, then you haven’t really understood it”. Substitute ‘lipid signalling’ for ‘quantum mechanics’ and you have my feelings on the subject.

We are used to hearing bad news about lipids in relation to disease, so I was pleased to read of some fascinating new developments in relation to resolvins and protectins, anti-inflammatory lipids derived from long-chain omega-3 fatty acids. It appears that there are a number of animal experiments to indicate that these lipids can ameliorate the effects of many bacterial and viral diseases. The final line of the abstract is “If the effects of these mediators translate from pre-clinical studies into successful clinical trials, they represent promising new strategies in managing infectious disease” (Russell, C.D. and Schwarze, J. The role of pro-resolution lipid mediators in infectious disease. Immunology, 141, 166-173 (2014); DOI). A more general review of the biochemistry of these lipids was published at the end of last year (Serhan, C.N. and Chiang, N. Resolution phase lipid mediators of inflammation: agonists of resolution. Curr. Opinion Pharmacol., 13, 632–640 (2013); DOI).

In the last years or so a number of papers have appeared that deal with arsenolipids in fish oils. These may consist of long-chain hydrocarbons with a terminal dimethylarsinoyl moiety, first described as recently as 2008, or fatty acids resembling those found conventionally but with a dimethylarsinoyl moiety replacing the terminal methyl group. I have lost count of how many of the latter have been reported to date but it must be more than twenty. One further type of arsenolipid with a long alkyl chain has now been reported that consists of cationic trimethylarsenio fatty alcohols of which two molecular species have so far been detected in fish oils (Amayo, K.O. et al. Novel identification of arsenolipids using chemical derivatizations in conjunction with RP-HPLC-ICPMS/ESMS. Anal. Chem., 85, 9321-9327 (2013); DOI).

A cationic trimethylarseno-fatty alcohol

Alkyl phospholipids are proving to be rather useful as pharmaceutical agents. Alkyl-lysophospholipids were first examined because they are more stable than acyl-lysophospholipids, which have proven biological activity, but synthetic alkylphospholipids lacking a glycerol moiety such as hexadecylphosphocholine (‘Miltefosine’) are proving of greater interest. The latter has been approved for application in cutaneous metastasis of breast cancer and visceral and cutaneous leishmaniasis. Now a new range of related molecules having lower toxicity are being tested against a variety of diseases, including those caused by pathogenic fungi, parasites and bacteria. A new review describes achievements in this area (Pachioni, J. de Almeida. et al. Alkylphospholipids - a promising class of chemotherapeutic agents with a broad pharmacological spectrum. J. Pharm. Pharm. Sci., 16, 742-759 (2013); ejournals.library.ualberta.ca/index.php/JPPS/article/view/20450). The article is open access.

Also open access, in line with ACS policy as it is in the first issue of the journal for the year, is a review on the methodology of lipidomics (Li, M. et al. Analytical methods in lipidomics and their applications. Anal. Chem., 86, 161-175 (2014); DOI).

So far, I have seen the terms ‘phospholipidomics’, ‘sphingolipidomics’, ‘glycolipidomics’, ‘neurolipidomics’, ‘steroidomics’, ‘endo-cannabinoidomics’ and ‘oxylipidomics’ in the literature, and now I have come across 'fatty acidomics'. While I am not entirely happy with the coining of new words in this way, they are at least preferable to the use of the term 'lipidomics' as a catch-all to describe an analysis of a single lipid class.

Trust a Scotsman to find a bargain. In recent years, it has become dogma in nutritional circles that dietary trans-fatty acids are detrimental to health. There are innumerable publications in the biological literature to document this, but it can be harder to find information on chemical properties. A new and substantial review in the ACS journal Chemical Reviews remedies this, and fortuitously, as it is in the first issue of the year, it is open access (Chatgilialoglu, C. et al. Lipid geometrical isomerism: from chemistry to biology and diagnostics. Chem. Rev., 114, 255-284 (2014); DOI). Amongst many topics, the review covers the analysis and characterization of trans fatty acids, natural sources and chemical reactivity. The same issue of the journal also contains two articles on the chemistry and biochemistry of carotenoids and retinoids, which should be of interest to biochemists (and also open access).

Another group of important biologically active fatty acids, which are currently attracting great interest, are the nitro-conjugated linoleic acids. A new paper in the ACS Journal of Organic Chemistry discusses the chemical synthesis and characterization of these fatty acids (Woodcock, S.R. et al. Biomimetic nitration of conjugated linoleic acid: formation and characterization of naturally occurring conjugated nitrodienes. J. Org. Chem., 79, 25-33 (2014); DOI). Studies of the biological properties should be facilitated by readier access to model compounds. Again as it is in the first issue of the year, this paper is open access.

There have been a number of articles in the last year discussing the putative role of palmitoleic acid (9-16:1) as a lipokine – a recently minted word to define a lipid hormone, i.e., it is an adipose tissue-derived molecule, which amongst other effects stimulates the action of insulin in muscle. However, the mechanism and the active form of the metabolite appear unclear. Last April in this blog, I speculated that no one seemed to have connected this with the finding that the family of Wnt proteins, which are central mediators of animal development, with profound influences on adipose tissue amongst other organs, have an unusual and essential acyl modification with palmitoleic acid at a conserved serine residue, at least in murine Wnt-3a, the most intensively studied form (Takada, R. et al. Monounsaturated fatty acid modification of Wnt protein: its role in Wnt secretion. Developmental Cell, 11, 791-801 (2006); DOI). Recent reviews have discussed both lipokines and Wnt proteins without making this physical connection. Am I being too speculative that this might be behind the mechanism for lipokine action? No one has commented on my suggestion so far.

Column chromatography on silicic acid has been a common means of separating glycolipid and phospholipid fractions from total lipid extracts for more than 50 years - longer than even I have been involved in the analysis of lipids. I have commented in these pages and elsewhere from time that there needed to be a re-appraisal of the methodology with modern adsorbents and with monitoring by modern instrumental methods. I am happy to say that this has now been done, although I can't say that I am surprised that the results are not very encouraging (Heinzelmann, S.M. et al. Critical assessment of glyco- and phospholipid separation by using silica chromatography. Appl. Environm. Microbiol., 80, 360-365 (2014); DOI). The method was applied to microbial samples as opposed to those of animal origin as in the original publication cited, but it is evident that the 'phospholipid' fraction can contain many other non-phospho components, including glycolipids, betaine lipids, and sulfoquinovosyldiacylglycerols. Modifying the conditions provided a relatively small improvement only.

In the days when I was active in research, my colleagues and I tended to favour solid-phase extraction columns and a bonded-amine phase for this type of separation, although recovery of acidic phospholipids was tedious.

January, 2014

Scottish thistle As far as I have read, dietary supplementation with DHA has little or no effect on the loss of cognitive ability in the elderly, although there may be health benefits in other areas. I prefer to take my fish oil the natural way in fish. However, it appears that there is plentiful evidence that dietary fish oil is beneficial at the other end of the age scale. It seems to be established that it helps with with behaviour and general school performance, for example. Two new reviews summarize the evidence (Kuratko, C.N. et al. The relationship of docosahexaenoic acid (DHA) with learning and behavior in healthy children: a review. Nutrients, 5, 2777-2810 (2013); DOI. Lane, K.E. and Derbyshire, E. Systematic review of omega-3 enriched foods and health. Brit. Food J., 116, 165-179 (2014); DOI).

I have commented before on the great advances that have been made possible in the area of plant sphingolipids by modern mass spectrometric methods, especially with respect to the glycosylinositol phosphoceramides, which are now known to be as important as the glycerophospholipids in cell membranes. A new study demonstrates that the overall structures can be very variable across species. Glycosylinositol phosphoceramides in algae differ from those in mosses, gymnosperms and monocots, while dicots contain the greatest complexity. Their composition in the model plant Arabidopsis thaliana is not typical of plant species in general (Cacas, J.-L. et al. Biochemical survey of the polar head of plant glycosylinositolphosphoceramides unravels broad diversity. Phytochemistry, 96, 191-200 (2013); DOI).

I have just been reading a useful general review of the biochemistry and function of the oligoglycosphingolipids, which I can recommend, especially as it is open access (D'Angelo, G. et al. Glycosphingolipids: synthesis and functions. FEBS J., 280, 6338-6353 (2013); DOI)

Issue 24 in December 2013 of FEBS Journal has a number of review articles under the heading of ‘Lipid signalling in health and disease’ edited by Daniela Corda and Maria Antonietta De Matteis. All are open access. I always like articles where the author uses his imagination to speculate on the origin and function of lipids, and I especially enjoyed reading one of these reviews (Michell, R.H. Inositol lipids: from an archaeal origin to phosphatidylinositol 3,5-bisphosphate faults in human disease. FEBS J., 280, 6281-6294 (2013); DOI). It appears that inositol lipids are ubiquitous in the Archaea, but occur only rarely in bacteria and other primitive organism, before assuming major importance in Eukaryotes. This paper lead me to an earlier one on a related topic, which I had missed when it first appeared and discusses how polar head groups that are common to bacteria and Archaea might have evolved (Koga, Y. Early evolution of membrane lipids: how did the lipid divide occur? J. Mol. Evol., 72, 274-282 (2011); DOI).

I am continually fascinated by recent discoveries of novel biochemical processes in which lipids are involved. Now it appears that endocannabinoids and lysophosphatidic acid are involved in key aspects of cocaine addiction. It is hoped that interference with the metabolism of these lipids may be of therapeutic value to addicts (Orio, L. et al. Lipid transmitter signaling as a new target for treatment of cocaine addiction: new roles for acylethanolamides and lysophosphatidic acid. Curr. Pharm. Design, 19, 7036-7049 (2013); DOI).

Biochemists may also be interested in an open access review dealing with lipids and the immune system (Dowds, C.M. et al. Lipid antigens in immunity. Biol. Chem., 395, 61-81 (2014); DOI).

It has long been known that sphingosine-1-phosphate (S1P) promotes cancer proliferation, survival and invasiveness in animal models, while ceramide has the opposite effects. The balance between the two lipids may be critical. This has of course been much more difficult to demonstrate in humans. Strong evidence that this is so has now been obtained in human brain tumours (Abuhusain, H.J. et al. A metabolic shift favoring sphingosine 1-phosphate at the expense of ceramide controls glioblastoma angiogenesis. J. Biol. Chem., 288, 37355-37364 (2013); DOI). The authors show that “S1P content was, on average, 9-fold higher in glioblastoma tissues compared with normal gray matter, whereas the most abundant form of ceramide in the brain, C₁₈ ceramide, was on average 5-fold lower”. The hope is that inhibitors of sphingosine kinase 1, a key enzyme is S1P biosynthesis, will prove to be effective anti-cancer agents.

The biological function of the related enzyme sphingosine kinase 2 is less well known, but it also is believed to be involved in the development of cancer. A new review discusses the evidence (Neubauer, H.A. and Pitson, S.M. Roles, regulation and inhibitors of sphingosine kinase 2. FEBS J., 280, 5317-5336 (2013); DOI).

While on the subject of sphingolipids, I will have to devote some time to reading a new review on the subject of sphingolipidoses, i.e., storage diseases caused by defects in the catabolism of these complex lipids (Sandhoff, K. Metabolic and cellular bases of sphingolipidoses. Biochem. Soc. Trans., 41, 1562-1568 (2013); DOI).

Perhaps I should take a greater interest in a report highlighted in Science Daily News that “elderly people with high serum vitamin E levels are less likely to suffer from memory disorders than their peers with lower levels”

This is how to teach lipid science - http://m.youtube.com/watch?v=6lrG65DdBl8 - with thanks to Michael Eskin!

The August issue of the journal Molecular Nutrition and Food Research (Volume 57, Issue 8, Pages 1305-1504) was devoted to the topic of ‘Lipidomics: Approaches and Applications in Nutrition Research’ (edited by Claus Schneider).

It has now been revealed that the phospholipid platelet activating factor (PAF) functions as an anti-obesity compound in an animal model (Sugatani, J. et al. Antiobese function of platelet-activating factor: increased adiposity in platelet-activating factor receptor-deficient mice with age. FASEB J., 28, 440-452 (2014); DOI). The lipid operates in this way through stimulation of its receptor in brown but not white adipose tissue. It appears that reduction of this activity may be responsible for increasing fat deposition as we age. The story made our national press in the U.K., and there is an interesting report on the Science Daily News website.

Until recently, it was believed that approximately 90% of cholesterol elimination from the body occurred via bile acids in humans. However, experiments with animal models now suggest that a significant amount may be secreted directly into the intestines by a process known as trans-intestinal cholesterol efflux. How this occurs and its relevance to humans are obviously of considerable clinical importance and are under active investigation. A new review in an open access journal summarises what is known (Jakulj, L. et al. Intestinal cholesterol secretion: future clinical implications. Neth. J. Med., 71, 459-465 (2013); (www.njmonline.nl/getpdf.php?t=a&id=10001021).

Blogs for the previous year (2013) can be located here..

© Bill Christie
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