Lipid Matters - A Personal Blog



Or "Lipids Matter". An occasional series of notes on publications or other items dealing with lipid science that seem to be of particular interest to the originator of this web page, Bill Christie. Inevitably, the selection is highly personal and subjective. The older entries are archived for at least a year in a separate web page here..


December 6th, 2017

Most readers today will not need me to explain the importance of lipid mediators in biology, but this was not always so. I recall attending an ICBL Congress in 1968 when a keynote speaker described prostaglandins as "a drug in search of a disease"! (The only virtue of growing older is that you remember such things). The earliest true pharmaceutical to come into general use and probably still that most widely used is aspirin, which is now known to inhibit the synthesis of the prostaglandins and certain other eicosanoids or modify their nature via its action on the cyclooxygenases. A fascinating new review describes how the full potential of aspirin and many other pharmaceuticals could not have been realized without the knowledge gained from lipidomic studies on the eicosanoid patterns in tissues in various clinical conditions (Stephenson, D.J. et al. Lipidomics in translational research and the clinical significance of lipid-based biomarkers. Translat. Res., 189, 13-29 (2017); DOI). For example, by revealing the pattern of eicosanoids during cardiovascular disease or in patients with pre-eclampsia, it became evident that low-doses of aspirin had great therapeutic potential. Many other benefits from lipidomic studies to such disease states as neurodegenerative diseases, cancer, sepsis and wound healing are discussed also in this review.

The tag "et al." has never been more useful than in a new publication in the Journal of Lipid Research, which has 94 authors (I don't guarantee the accuracy of my count) (Bowden, J.A. et al. Harmonizing lipidomics: NIST interlaboratory comparison exercise for lipidomics using SRM 1950-Metabolites in Frozen Human Plasma. J. Lipid Res., 58, 2275-2288 (2017); DOI). John A. Bowden was fortunate in that his name is first in the alphabetical order of authors so takes pride of place in the list. Joking aside, I suspect that this will come to be regarded as a seminal paper in the science of lipidomics, although it is a pity that it is not open access. However, like me, you may still be able to get hold of a manuscript copy if not the final printed form via the journal.

November 29th, 2017

Scottish thistle In plants, the external cuticle layer has many of the same functions as the skin in animals in that it acts to prevent water loss while providing a barrier against pathogenic bacteria and fungi as well as insect predators. Lipids play key roles in both although their natures are very different; in skin, ceramides and other sphingolipids are the essential components, but in plants there is a complex polyester that includes polyhydroxy and dibasic fatty acids and this is overlaid by a layer of wax. While some have argued that plant waxes are the most abundant lipids on earth, it is the polyester component of the cuticle that is attracting most interest at the moment because of its structural properties and the potential to modify it to increase crop yields or as a future source of bio-plastics. Incidentally, cutins from decaying plants are also the source of important lipid components of soils. The Journal of Experimental Botany has devoted a special issue to the topic with an introductory article that summarizes many of the key factors and is open access (Domínguez, E. et al. The plant cuticle: old challenges, new perspectives. J. Exp. Bot., 68, 5251-5255 (2017);  DOI).

Among the novel lipids of skin are ceramides containing estolide linked fatty acid constituents. However, it is those with free carboxyl groups or 'FAHFA' (Fatty Acid ester of Hydroxy Fatty Acid) in other tissues that continue to fascinate. A range of (O-acyl)-ω-hydroxy-fatty acids (the hydroxyl group is terminal not centrally located) with up to 52 carbon chain lengths have been found in equine amniotic fluid, together with many other interesting lipid species (Wood, P.L. et al. Lipidomics of equine amniotic fluid: Identification of amphiphilic (O-acyl)-ω-hydroxy-fatty acids. Theriogenology, 105, 120-125 (2018);  DOI). Similar fatty acid estolides have been found in sperm and meibomian glands, but their function is still a matter for speculation.

The journal Seminars in Immunology has devoted a special issue (Volume 33, Pages 1-74, October 2017) to the topic of "Leukotriene B4 mediated inflammation" (edited by Bodduluri Haribabu).

November 22nd, 2017

Of all the health food supplements that are available, it appears that omega-3 fatty acids from fish oil preparations are the most popular. While reputable manufacturers take great pains over the quality of their products, they have no control of how they are stored in supermarkets or whether consumers store them properly or simply let them sit in medicine cabinets.· I am sure that oxidation products often develop rapidly, although off-flavours may be disguised by the encapsulation process.·· A new review summarizes the biological properties of compounds derived from peroxidation of omega-3 polyunsaturated fatty acids,· including aldehydes, isoprostanes· and more (Wang, W. et al. Chemistry and biology of ω-3 PUFA peroxidation-derived· compounds. Prostaglandins Other Lipid Mediators, 132, 84-91 (2017);  DOI).· Many potential adverse effects are known, and the authors are concerned that variable amounts of such impurities· might explain the mixed results obtained in some nutritional studies. Personally, I prefer fresh fish to fish oil supplements.

S-Palmitoylation is increasingly being seen as an important way· of regulating the activities of potential membrane proteins.· In humans, 23 palmitoyl transferases are known to exist with a conserved cysteine-rich domain containing· a distinctive aspartate-histidine-histidine-cysteine (DHHC) motif, which is required for activity.· On the other hand, no conserved amino acid sequence has yet been identified in target proteins.· A new open access publication describes interesting mass spectrometry methodology to reveal· that there is a random palmitoylation process that depends simply upon the accessible· of cysteines in proteins to the palmitoyl transferases (Rodenburg, R.N.P. et al. Stochastic palmitoylation· of accessible cysteines in membrane proteins revealed by native mass spectrometry. Nature Commun., 8, 1280 (2017);·  DOI).

November 15th, 2017

The hedgehog proteins are among my favourite molecules as they stick up two metaphorical fingers to nutritionists. The first such finger is cholesterol, which is covalently bound to the C-terminus, while the second is palmitic acid covalently bound to the N-terminus. Although they are anathema in some quarters, the vital importance of the two much maligned lipid components is clearly demonstrated since hedgehog proteins have a major role in signalling during the differentiation of cells in the development of all embryos from Drosophila to fish to humans and are required for an extensive range of processes, from the control of left-right asymmetry of the body to the specification of individual cell types within the brain and limb development. They are the subject of a new open access review (Blassberg, R. and Jacob, J. Lipid metabolism fattens up hedgehog signaling. BMC Biology, 15, 95 (2017);  DOI).

Membrane microdomains termed 'rafts' have long been believed to be formed spontaneously in the outer leaflet of the plasma membrane by the physical chemical association of cholesterol, sphingolipids and membrane proteins. They act to compartmentalize and provide a platform for the last and thereby separate different biochemical functions. However, there is a conflicting view of the prevailing raft hypothesis based on studies by high-resolution secondary ion mass spectrometry that suggests that sphingolipids are concentrated in micrometer-scale membrane domains while cholesterol is evenly distributed within the plasma membrane. In this model, sphingolipid distribution in the plasma membrane is dependent on the cytoskeleton, but not on favorable interactions with cholesterol. An open access review, published earlier this year, discusses this alternative theory (Kraft, M.L. Sphingolipid organization in the plasma membrane and the mechanisms that influence it. Front. Cell Dev. Biol., 4, 154 (2017);  DOI).

I was under the impression that I had a good understanding of the nature of bile acids, which are important cholesterol metabolites with essential functions in digestions and signalling. However, I have just come across a paper that describes a small group of bile acids with planar structures of which I had no previous knowledge (Shiffka, S.J. et al. Planar bile acids in health and disease. Biochim. Biophys. Acta, Biomembranes, 1859, 2269-2276 (2017);  DOI). These are found in humans during infancy and in a few disease states, but not otherwise. In evolutionary terms, they may be related to the ancestral bile acids.

November 8th, 2017

Another special journal issue deals with the important topic of specialized pro-resolving mediators, i.e. resolvins, protectins and maresins, (Dalli, J. (Editor) The physiology and pharmacology of specialized pro-resolving mediators. Molecular Aspects of Medicine Volume 58, Pages 1-130 (December 2017)). The editor's own contribution is open access and has the intriguing title of "Does promoting resolution instead of inhibiting inflammation represent the new paradigm in treating infections?" Uncontrolled inflammation as occurs during sepsis is an increasing problem in our hospitals, and the resolvins, protectins and maresins have been shown to "actively reprogram the immune response to promote clearance of invading pathogens, and counter-regulate the production of inflammation-initiating molecules". Clinical trials of these lipids and mimetics against a number of inflammatory conditions, including sepsis, are now in progress and they are discussed in other reviews in this issue.

In contrast, cholesterol 5,6-epoxide formed non-enzymatically was for some time believed to be a causitive agent in cancer, but it has now been established that downstream metabolites are in fact responsible (Voisin, M. et al. Identification of a tumor-promoter cholesterol metabolite in human breast cancers acting through the glucocorticoid receptor. PNAS, 114, E9346-E9355 (2017);  DOI). A cholesterol epoxide hydrolase converts cholesterol 5,6-epoxide into cholestane-3β,5α,6β-triol, which is transformed by 11β-hydroxysteroid-dehydrogenase-type-2 into the oncometabolite 6-oxo-cholestan-3β,5α-diol. By binding to the glucocorticoid receptor, this last metabolite stimulates the growth of breast cancer cells. It is hoped that targeting the enzymes involved in this metabolic process may lead to new treatments for breast and other cancers.

It has been less easy to establish definitively the biological effects of other oxysterols as so much cholesterol may be present in experiments in vitro that unwanted metabolites may be introduced inadvertently. However, there is good evidence for the involvement of 27-hydroxycholesterol as an endogenous and selective modulator of estrogen receptors with implications for a number of disease states including neurodegenerative diseases, atherosclerosis, osteoporosis and some cancers (He, S.S. and Nelson, E.R. 27-Hydroxycholesterol, an endogenous selective estrogen receptor modulator. Maturitas, 104, 29-35 (2017);  DOI).

Every year I seem to find a news item highlighting the poor job prospects for new PhD students and I usually predict that nothing will change. This is still true - see Nature News!

November 1st, 2017

While I have been enjoying the sunshine of the Canary Islands, the world of lipids has been turning rapidly. It seems most unfair that after returning from 30°C on a beach in Gran Canaria to 11°C and thermal underwear in Scotland, in addition to scanning many new research papers and other chores, I have now to try to assimilate three special review volumes to update my Lipid Essentials pages, i.e. "Focus on plasmalogens" in FEBS Letters (Volume 591, Issue 20) and open access, "Oxysterols and Phytosterols in Human Health" (edited by Charbel Massaad, Luigi Luliano and Gérard Lizard) in Chemistry and Physics of Lipids (Volume 207, Part B) and "Microbe and host lipids", edited by Jérôme Nigou, Lhousseine Touqui, Michel Record in Biochimie (Volume 141).

Sometimes it is the science oddities rather than major new research findings in terms of lipid metabolism that catch the eye. For example, I was intrigued by a report in the popular scientific press of preen gland lipids being identified in the fossil of a 48-million-year-old bird. It appears that the composition was sufficiently similar to that of the waxes in modern birds to enable an unequivocal identification.

Another fascinating if more relevant observation in relation to human health is carried in a paper that demonstrates that gangliosides are essential for hearing in that their presence in membrane rafts is required to maintain the structural and functional integrity of hair cells in the ear (Inokuchi, J. et al. Gangliosides and hearing. Biochim. Biophys. Acta, General Subjects, 1861, 2485-2493 (2017);  DOI). If you have an interest in these sphingoglycolipids there is a second publication in the same journal issue dealing with gangliosides, rafts and inflammation.

October 18th, 2017

Scottish thistle For decades, plant biochemists have been looking for a magic bullet that will enable them to alter the lipid composition of membranes in plants to make them less sensitive to cold. Some progress has been made by introducing desaturase genes, and the composition of phosphatidylglycerol appears to be especially important. However, a new review provides a broader context to the problem by comparing the factors that differentiate the model plant Arabidopsis from a close relative that is especially hardy (Barrero-Sicilia, C. et al. Lipid remodelling: Unravelling the response to cold stress in Arabidopsis and its extremophile relative Eutrema salsugineum. Plant Sci., 263, 194-200 (2017);  DOI). It is evident that there are many different factors involved including many compounds other than lipids (sugars, nitrogen compounds and proteins) that are required to conserve membrane integrity during cold acclimatization. Then, we have to understand the role of signalling lipids in controlling how membranes respond to change, where it appears that sphingolipid analogues of sphingosine-1-phosphate are especially important. Despite this complexity, the authors seem to be confident that further lipidomic studies in combination with genome editing in a precise manner "will enable the development of breeding strategies that deliver climate resilient crops."

The nature of the challenges to modifying lipid compositions in plants is illustrated by a further review in the same journal issue, where the authors point out that to introduce new fatty acids of potential industrial interest to crop plants it is rarely possible to introduce a single biosynthetic gene. It is always necessary to add futher genes for enzymes that can handle the new fatty acid and complete the transfer to a safe esterified state (Aznar-Moreno, J.A. and Durrett, T.P. Metabolic engineering of unusual lipids in the synthetic biology era. Plant Sci., 263, 126-131 (2017);  DOI).

I suppose it was not really a surprise to learn that Elsevier and the American Chemical Society have filed a lawsuit with the aim of removing copyrighted material from ResearchGate (see Nature News). I have mixed feelings about this, coloured of course by my personal circumstances. My former employer allows me access to a wide range of biological publications from the big three publishers together with a range of journals to which it subscribes, but I can't access chemistry journals or many of those with a medical slant. While I could use interlibrary loan facilities, this bears a significant cost and I cannot justify this when I am only going to use the information I glean for my website and not for research purposes. The prices required by journals for digital access are so unreasonable - far higher than those for interlibrary loan photocopies - that it is no wonder that scientists turn to ResearchGate in the hope of finding copies there. I have to confess that I do this from time to time, and often find preprints rather than the final publications and these are more than adequate for my purposes. Would this be a fair compromise?

As you may guess from the title, I read another review with great interest this week (Bustos, V. and Partridge, L. Good ol' fat: links between lipid signaling and longevity. Trends Biochem. Sci., 42, 812-823 (2017);  DOI). While it is a fascinating account of the use of the nematode worm Caenorhabditis elegans in studies of this kind, it is apparent again that there is no magic bullet alas. However, there is clear evidence that dietary restriction helps, and oleoylethanolamide does extend life in worms at least via its signalling properties. There is also something to be said for higher relative dietary proportions of oleate in general. If it will keep me compos mentis as well for longer, I will volunteer as a guinea pig.

Last month, I highlighted a multiauthor paper describing protocols for the use of NMR spectroscopy for the analysis of lipoprotein classes. Now a new review publication provides a general overview of the techniques involved (Aru, V. et al. Quantification of lipoprotein profiles by nuclear magnetic resonance spectroscopy and multivariate data analysis. Trends Anal. Chem., 94, 210-219 (2017);  DOI).

October 11th, 2017

Developments in mass spectrometric methodology has turned the analysis of lipids into a new science - lipidomics, but I must confess that I tend to pay relatively little attention to the applications of nuclear magnetic resonance spectroscopy to lipid science. The latter lacks the sensitivity of MS methods, but it can make an invaluable contribution to lipid analysis and structure identifications nonetheless, especially when sample size is not limiting. Indeed, NMR spectroscopy may have advantages in settling stereochemical problems. A new review of the subject is therefore timely (Li, J. et al. Applications of nuclear magnetic resonance in lipid analyses: An emerging powerful tool for lipidomics studies. Prog. Lipid Res., 68, 37-56 (2013);  DOI). If the DOI link doesn't work, blame Elsevier.

A new review on the subject of "steryl esters" in BBA reminded me that some years ago when I raised a nomenclatural point with IUPAC-IUB, they rebuked me for using the generic term "cholesteryl esters", which I was told should correctly be termed "cholesterol esters". "Cholesteryl" should be applied only when describing individual lipid species, e.g. cholesteryl palmitate, cholesteryl oleate, etc. Over to you Lipid Maps!

Just has Christmas comes earlier every year in the shops at least, so does the new publishing year roll out earlier. In my literature survey last month, I cited my first 2018 reference! The journal Food Chemistry wins the race every year.

October 4th, 2017

Humans differ from all other animals in that we do not make the sialic acid N-glycolylneuraminic acid (Neu5Gc) for incorporation into gangliosides and glycoproteins. This is believed to have occurred during evolution soon after we diverged from a common ancestor with the great apes and may have had profound implications for the development of the human brain. It could also mean that there might have been a fertility barrier between us and other species of hominids. Proving these conjectures has seemed impossible, but it has now been established that sufficient glycoproteins linked to Neu5Gc are present in intact form in fossil bones to enable determination of its presence. It will be fascinating to see how the story now unfolds. There is a popular account of the research in Science Daily with a link to the original publication for those needing further details.

Just as I was working my way through one special issue, Biochimica Biophysica Acta has brought forward another that deals with "Bacterial Lipids" and edited by Russell E. Bishop; I suspect it will keep me busy updating my web pages here for some time.

A fascinating story has emerged in a new publication that demonstrates how the liver undergoes a metabolic switch to provide fuel for brown fat thermogenesis by producing acylcarnitines. Under cold stimulation, white adipocytes release free fatty acids for acylcarnitine production in the liver to be supplied in the circulation to brown adipose tissue. At the same time, uptake of acylcarnitines into white adipose tissue and liver is blocked (Simcox, J. et al. Global analysis of plasma lipids identifies liver-derived acylcarnitines as a fuel source for brown fat thermogenesis. Cell Metab., 26, 509-522.e6 (2017);  DOI). While the quantitative aspects appear to require further work, the process is certainly an elegant one. I don't have access to the original paper yet, but the journal issue contains a commentary or 'preview' that describes the work and is accessible (if you know where to look via Google).

September 27th, 2017

Scottish thistleWhile my weekly literature searches keep me reasonably up-to-date, the algorithm I use is far from perfect and I have just come across a fascinating lipid story that started in 2012 and continues to the present. First a little background - choanoflagellates are motile microbial eukaryotes that live in aquatic environments and feed on bacteria. They are believed to be the closest living relatives of animals and are normally unicellular. However, it has now been demonstrated that on exposure to novel sulfonolipid analogues of ceramides related to the capnoids and produced by Algoriphagus machipongonensis, a marine bacterium that serves as its prey, the choanoflagellate, Salpingoeca rosetta, forms multicellular 'rosettes' in a manner that may provide insights into how multicellularity evolved in animals. Two such lipids have been isolated and characterized and they have been termed 'Rosette-Inducing Factors' - RIF-1 (illustrated) and RIF-2. Both have capnoid bases attached to 2-hydroxy,iso-methylbranched fatty acids, but RIF-2 differs from RIF-1 in the nature of the capnoid base component. S. rosetta is extraordinarily sensitive to RIF-1 and is induced to form rosettes at femtomolar (10-15M) concentrations. A second lipid class, lysophosphatidylethanolamines, produced also by the symbiotic bacteria elicits no response on its own but acts synergistically with the RIFs to maximize the activity of the latter.

Inducer/inhibitors of rosette formation in Choanoflagellates

A third lipid class now enters the picture as the same bacterial species also produces an inhibitor of rosette formation termed 'Inhibitor of Rosettes (IOR-1)' in the form of a further novel sulfonolipid, which is related structurally to the capnoid bases but with a hydroxyl group replacing the amine group to give the rare syn-diol configuration, i.e. 2S, 3R stereochemistry. It has been determined that there is an absolute requirement for the observed stereochemistry for all of these metabolites to exert their functions. To follow the story in greater detail, see the latest publication from the research group responsible for the work (Woznica, A. et al. Bacterial lipids activate, synergize, and inhibit a developmental switch in choanoflagellates. PNAS, 28, 7894-7899 (2016);  DOI).

September 20th, 2017

Although the evaporative-light scattering detector (ELSD) has its limitations in terms of linearity of response and sensitivity, it was the first truly universal detector for HPLC of lipids at a time when mass spectrometry interfacing was prohibitively expensive for most researchers. It enabled great strides in the development both of mobile and stationary phases for lipid separations and still has value for this purpose today. When charged aerosol detectors (CAD) were introduced, they seemed a step forward but they have never taken off. In part, this seemed to be because impurities in solvents caused problems and ionic species in mobile phases, which are necessary for elution of phospholipids, were especially troublesome. As liquid chromatography-mass spectrometry systems have become more affordable, the perceived need for alternative detectors may have lessened, but I believe the ELSD and CAD will remain useful tools, especially for development of novel elution systems and for semi-preparative applications (with stream splitters). A new publication presents a more positive view of the CAD than I have seen up till now, while also comparing the merits of various ionization techniques employed in mass spectrometry interfacing; atmospheric pressure photoionization (APPI) seems a clear winner (Abreu, S. et al. Optimization of normal phase chromatographic conditions for lipid analysis and comparison of associated detection techniques. J. Chromatogr. A, 1514, 54-71 (2017);  DOI). The paper also describes a rather novel and comprehensive elution scheme for normal-phase separation of lipid classes with silica as the stationary phase and a complex gradient in the mobile phase with ethyl acetate as a major component.

When I saw that a new review had been published on lipids in plant defense, I immediately assumed that this would deal primarily with the oxylipins and then mainly with jasmonates, but it proved much more than that. In fact, it covers a full range of lipids from fatty acids, via complex lipids to wax esters, and provides a fascinating and comprehensive overview of the subject (Lim, G.H. et al. Fatty acid- and lipid-mediated signaling in plant defense. Annu. Rev. Phytopath., 55, 505-536 (2017);  DOI).

The latest online issue of Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids (Volume 1862, Issue 10, Part B, Pages 1129-1284 (October 2017)) covers the topic of "Recent Advances in Lipid Droplet Biology" and is edited by Rosalind A. Coleman and Matthijs K.C. Hesselink.

September 13th, 2017

"A tale of two lipids" may sound Dickensian, but it aptly describes a paper drawn to my attention by the newsletter of the Fats of Life; in truth, it is anything but Dickensian (Houthuijzen, J.M. et al. Fatty acid 16:4(n-3) stimulates a GPR120-induced signaling cascade in splenic macrophages to promote chemotherapy resistance. FASEB J., 31, 2195-2209 (2017);   DOI). I have encountered hexadeca-4,7,10,13-tetraenoic acid or 16:4(n-3) at trace levels from time to time in marine samples, but never in animal tissues. Yet it is generated when platinum salts are administered as part of an anticancer chemotherapy regime where it induces systemic resistance to a broad range of DNA-damaging effects. The new study demonstrates that this fatty acid acts via a specific receptor to induce the synthesis in macrophages of the second unusual lipid in the tale, i.e. lysophosphatidylcholine containing the fatty acid 24:1, and this is also shown to be a resistance-inducing lipid mediator. Again, I don't recall seeing this particular molecular species when analysing animal lipids, though I must admit that it would be easy to overlook.

Nature has an interesting story concerning "predatory journals", which I suppose must be defined as those designed to milk revenue from researchers rather than to inform. While I have heard this epithet applied to the big three commercial publishers from time to time, the authors appear to refer to about ~2000 other journals, which are often published in third world countries and lack proper editorial boards or refereeing panels. It seems that many reputable authors are using them while unaware of the true situation. I can think of a few review articles, which have come from such journals and which I may have cited in this website from time to time because they appeared useful to me in updating my web pages, especially as many are part of the open access trend. In fairness to myself, I usually check whether the authors come from reputable institutions. Unfortunately, no one seems to have any idea what to do about the problem other than to keep researchers informed of the worst examples, and I suspect any solution would have to emerge sector by sector.

The journal Neuropharmacology (Volume 124, Pages 1-170 (15 September 2017)) is a special issue devoted to the topic of "A New Dawn in Cannabinoid Neurobiology", edited by Joseph F. Cheer and Yasmin L. Hurd. Many of the papers deal with the endocannabinoids.

September 6th, 2017

Sulfoquinovosyldiacylglycerols are key lipids in photosynthesis and thence for the survival of all advanced life as I discussed in my blog earlier in the year. A recent paper demonstrates that the positional distributions of fatty acids in this lipid can be determined by mass spectrometry (Granafei, S. et al. Unambiguous regiochemical assignment of sulfoquinovosyl mono- and diacylglycerols in parsley and spinach leaves by liquid chromatography/electrospray ionization sequential mass spectrometry assisted by regioselective enzymatic hydrolysis. Rapid Commun. Mass Spectrom., 31, 1499-1509 (2017);   DOI). One of the tools the authors used to validate their results was to generate the 2-monoacyl-sn-glycerol species by the action of a regiospecific lipase (although the positional data are not tabulated). A few weeks ago I bemoaned the fact that data for positional distributions of fatty acids in complex glycerolipids were only rarely published nowadays, as this is much easier for comparison purposes (and arguably for studies of biological functions) than vast tables of molecular species data. While it is technically possible to accomplish this by MS, I suspect that the precision of the methodology leaves something to be desired. This paper has inspired me to consider whether a useful complementary approach to the analysis of phospholipids especially might be to analyse lipid extracts before and after hydrolysis by enzymes that are specific for either the sn-1 or sn-2 positions, e.g. the sn-1 selective hydrolase used in the above study or an sn-2 specific enzyme such as the phospholipase A2 of snake venom. I would love to see a paper tabulating comparison data for stereospecific distributions of fatty acids in any complex glycerolipid obtained by mass spectrometry with and without enzyme hydrolysis and ideally alongside data obtained by classical methods. It might be a useful student project for someone.

Lysoglycosphingolipids are only rarely discussed in the literature, but they do have considerable biological importance and a new publication describes new sensitive methodology to determine their occurrence in body fluids in relation to screening for sphingolipidoses (Pettazzoni, M. et al. LC-MS/MS multiplex analysis of lysosphingolipids in plasma and amniotic fluid: A novel tool for the screening of sphingolipidoses and Niemann-Pick type C disease. PLOS One, 12, e0181700 (2017);   DOI).

If my knowledge of the practicalities of mass spectrometry is somewhat outdated, I have to confess that my understanding of what can be accomplished by NMR spectroscopy has fallen even further behind. However, I do my best to keep up and read with great interest a new open access publication dealing with the use of this technique in the analysis of lipoproteins (Centelles, S.M. et al. Toward reliable lipoprotein particle predictions from NMR spectra of human blood: an interlaboratory ring test. Anal. Chem., 89, 8004-8012;   DOI). I remember well how tedious it was to analyse lipoprotein classes by ultracentrifugation or high-performance liquid chromatography. This new paper describes methodology that has advantages in terms of high reproducibility and speed, and appears to be especially suitable for studies involving large numbers of subjects. The separation techniques will always be needed, but the more information that can be obtained by other means the better especially when standardized protocols are available.

August 30th, 2017

Scottish thistle Every week there is a report in the literature of a novel lipid being found in some exotic organism. Perhaps more surprising is how often new lipid structures are revealed in human tissues, and there are two good examples this week. While improvements in technology are often behind new discoveries, another explanation is that the authors have simply looked closer at minor components, or perhaps it is a bit of both. Ion mobility mass spectrometry appears to offer new opportunities in terms of separation and analysis of complex glycosphingolipids according to the charge state, the carbohydrate chain length and the degree of sialylation or other substitution with no requirement for a chromatography step, and a new report describes an application to brain lipids in which a large numbers of novel gangliosides modified with acetyl groups were discovered (Sarbu, M. et al. Electrospray ionization ion mobility mass spectrometry provides novel insights into the pattern and activity of fetal hippocampus gangliosides. Biochimie, 139, 81-94 (2017);   DOI). Last year, I commented on a paper from the same laboratory, where novel sialylated gangliosides were found in fetal brain by the same methodology.

The second relevant report is of the discovery of novel cholesterol esters containing estolide bound fatty acids in vernix caseosa, the natural biofilm on the skin of new-born babies (Kalužíková, A. et al. Cholesteryl esters of ω-(O-acyl)-hydroxy fatty acids in vernix caseosa. J. Lipid Res., 58, 1579-1590 (2017);   DOI). By means of reversed-phase liquid chromatography linked to mass spectrometry with atmospheric pressure chemical ionization, approximately 300 molecular species of this new lipid class were identified, with the most abundant containing a 32:1 ω-hydroxy fatty acid linked to those of a more conventional kind. I was aware of vernix caseosa as a source of wax esters containing a complex mixture of branched-chain fatty acids, but they are are very different in nature from these new lipids.

August 23rd, 2017

It is now commonplace to learn of how lipids are involved in various human disease states from the standpoint of errors in metabolism. On the other hand, there is recent evidence that bacteria and their lipids may be involved in what were formerly considered purely metabolic diseases. For example, it has now been reported that significant amounts of rhamnolipids are found in serum from patients with Alzheimer's disease (Andreadou, E. et al. Rhamnolipids, microbial virulence factors, in Alzheimer's disease. J. Alzheimer's Dis., 59, 209-222 (2017);   DOI). These powerful surfactants were first found in Pseudomonas aeruginosa but are now known from other bacterial species. While the connection to the pathology of the disease remains to be proven, it is certainly food for thought. A second study still in press suggests that lipoamino acids/peptides found in commensal Bacteriodetes bacteria of the gut and the oral cavity may contribute to the pathogenesis of TLR2-dependent atherosclerosis through deposition and metabolism in artery walls (Nemati, R, et al. Deposition and hydrolysis of serine dipeptide lipids of bacteroidetes bacteria in human arteries: relationship to atherosclerosis. J. Lipid Res., in press.   DOI).

I have always enjoyed the video articles in JoVE - The Journal of Visualized Experiments. Even when the particular protocol is not of direct interest, I found that I could always learn something from watching how others go about a task in the lab. Regretfully, it seems they have now changed their open access policy, so I won't be able to view a recent article that I would otherwise have hoped to consult (Williamson, K. and Hatzakis, E. NMR spectroscopy as a robust tool for the rapid evaluation of the lipid profile of fish oil supplements. JOVE-J. Vis. Exp., 123, e55547 (2017);   DOI).

Further to my comments in last week's blog on the potential confusion that can arise from using abbreviations - I have been reminded that DHA is the widely used abbreviation both for docosahexaenoic acid (22:6(n-3)) and for the glycerol precursor dihydroxyacetone in the lipid literature.

A special issue of the journal Biochimica et Biophysica Acta (BBA), Molecular Cell Research (Volume 1864, Issue 9, Pages 1435-1524 (September 2017)) deals with a topic relevant to many aspects of lipid biosynthesis, i.e. "Membrane Contact Sites" (edited by Benoît Kornmann and Christian Ungermann).

August 16th, 2017

Phosphatidylcholine and phosphatidylethanolamine can hardly be considered as neglected as they are the most abundant lipids in most cellular membranes in animals. On the other hand, I am not sure that the full range of their biological properties other than as membrane building blocks is always recognized. A new review is certainly helpful and has enabled me to update my pages here (van der Veen, J.N. et al. The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease. Biochim. Biophys. Acta, Biomembranes, 1859, 1558-1572 (2017);   DOI). For example, the role of phosphatidylcholine in lipoprotein metabolism is well known, but I was not aware that phosphatidylethanolamine is present in relatively high concentrations in newly secreted VLDL particles and that this lipid is almost certainly involved in VLDL assembly and/or secretion. On the other hand, it is rapidly and efficiently removed from the VLDL in the circulation but where and how?

One of my pet hates to which I refer here from time to time is the excessive and often unnecessary use of abbreviations and acronyms in scientific papers and especially when they are used in titles. They are a convenience for authors but a nuisance for readers. It seems that every technique, every enzyme, every gene and every metabolite now has its own abbreviation. Of course, I am not arguing that these be shunned entirely, and Lipid Maps, for example, have set out a set of recommended abbreviations for lipid classes that I have used from time to time and find useful especially in figures. In the publication cited above, PC and PE are used throughout in a sensible way. On the other hand, I often find an abbreviation is defined on page 2 of a paper and is then not used again until page 10 when I have to scramble back through to find what it means. A few weeks ago I mentioned that the abbreviation MGDG was used unnecessarily in the title of a publication to replace the one-word lipid class. Of course, it all depends on context; FA means 'fatty acid' in the lipid literature, but it can also mean 'Football Association' and something rather rude. PC can mean 'phosphatidylcholine', 'politically correct', 'police constable' or 'personal computer'. I am not one of the texting generation, who have their own set of abbreviations and may consider my comments are OTT ('over the top') or even ATP ('ATypical Pedantry' - I just made that up - OK). For the moment, I'll let the thought RIP.

August 9th, 2017

In writing this blog, I often allude to those lipids that are most often cited and are therefore actively researched. However, there are a few lipids that appear to be neglected in my opinion. For example, the non-acidic glycosyldiacylglycerols of animal tissues are rarely mentioned in the literature these days. There was a flurry of activity in the 1990s but little since. As they tend to be minor components, they are easily missed, although those in saliva and related secretions may have important functions in these tissues. Another explanation for the neglect may be that they are removed from lipid extracts as part of a procedure for removing glycerolipids to produce pure sphingoglycolipid preparations for analysis. While the acidic glycosyldiacylglycerol seminolipid does feature in many publications in relation to its function in male reproductive tissues, you will struggle to find much on its occurrence and function in brain and nervous tissues. In brain, some of these lipids may be produced adventitiously by the same enzymes that produce comparable sphingolipids, but they may still have distinct functions of their own.

Cytidine diphosphate diacylglycerol (CDP-DAG) is a key intermediate in the biosynthesis of phospholipids so features in innumerable biochemical studies, but what about its natural occurrence and composition in tissues. Just try to find data! Is the explanation is that its natural occurrence is too low and modern mass spectrometric methods are not sufficiently sensitive, or that it is too unstable, or that analysts are simply not looking for it?

Two important journal issues have just come to my attention - Biochimica et Biophysica Acta (BBA), Biomembranes (Volume 1859, Issue 9, Part B, Pages 1493-1748, September 2017) dealing with the topic of "Membrane Lipid Therapy: Drugs Targeting Biomembranes" and edited by Pablo V. Escribá - and Free Radical Biology and Medicine (Volume 111, Pages 1-344, October 2017) on the theme of "4-Hydroxynonenal and Related Lipid Peroxidation Products" and edited by Giuseppe Poli and Neven Zarkovic.

August 2nd, 2017

The opening sentence of a new open-access publication is thought provoking - "The major light-harvesting complex (LHCII) found in the chloroplasts of green plants contains more than half of the chlorophylls (Chl) and is the most abundant membrane protein on earth" (Seiwert, D. et al. The non-bilayer lipid MGDG stabilizes the major light-harvesting complex (LHCII) against unfolding. Sci. Rep., 7, 5158 (2017);  DOI). It must also be the most important protein for advanced life on earth as all the oxygen in the atmosphere is produced as a byproduct of the photosynthesis reaction. Monogalactosyldiacylglycerols for those of you unfamiliar with the abbreviation in the title have a conical structure and do not form bilayers, but their shape appears to match that of the trimeric LHCII complex and stabilize it while modulating the folding, conformation and function of the protein components.

The importance of the physical properties of lipids to the functions of animal organs is also illustrated by two publications in a recent issue of the Journal of Biological Chemistry. Over the years, I have read innumerable suggestions as to why docosahexaenoic acid (DHA) is important in tissues, but especially in relation to visual acuity. It now appears that its role in phospholipids is primarily to maintain the disc shape in photoreceptor cells (Shindou, H. et al. Docosahexaenoic acid preserves visual function by maintaining correct disc morphology in retinal photoreceptor cells. J. Biol. Chem., 292, 12054-12064 (2017);  DOI). Cellular membrane containing DHA in the phospholipids are more flexible than those containing arachidonic acid and other fatty acids, and they may also increase the stability and function of rhodopsin. Similarly, during spermatogenesis, DHA-containing phospholipids provide membranes in spermatids with the physicochemical properties needed for normal cellular processes (Iizuka-Hishikawa, Y. et al. Lysophosphatidic acid acyltransferase 3 tunes the membrane status of germ cells by incorporating docosahexaenoic acid during spermatogenesis. J. Biol. Chem., 292, 12065-12076 (2017);  DOI). The second of these papers is the authors' choice and therefore open access.

The latest issue of the journal Molecular Aspects of Medicine (Volume 56, Pages 1-110 (August, 2017)) deals with the theme of "Bile acids, roles in integrative physiology and pathophysiology" (edited by David H. Volle).


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Author: William W. Christie Updated: December 06th, 2017 Credits/disclaimer LipidWeb logo

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