Lipid Matters - Archive of Older Blogs - 2013

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 2013 are archived, while those for other years can be accessed from the foot of the current blog page.

December, 2013

Scottish thistle In a blog, a few weeks ago I commented on the limited number of real applications to lipid analysis afforded by supercritical fluid chromatography. Perhaps I should have made it more clear that I was referring to the use of carbon dioxide on its own as the mobile phase to enable flame-ionization detection. Of course, there are much greater opportunities if modifier solvents can be added with mass spectrometry as the detection system. I was reminded of this by new paper on the use of the technique to analyse Lipid A, which must have been a considerable technical challenge (Chen, Y.B. et al. Supercritical fluid chromatography-tandem mass spectrometry for the analysis of lipid A. Anal. Methods, 5, 6864-6869 (2013); DOI).

Plant biochemists were at the forefront of work on the enzymology of sphingoid base synthesis, and their work simplified the characterization of the related enzymes in animal tissues. Subsequently, work on sphingolipids in plants declined, but there has been a major renaissance in recent years. A new paper reports that presence of phytoceramide-1-phosphate in cabbage leaves for the first time (Tanaka, T. et al. Identification of a sphingolipid-specific phospholipase D activity associated with the generation of phytoceramide-1-phosphate in cabbage leaves. FEBS J., 280, 3797-3809 (2013); DOI). The precursor is believed to be glycosylinositol phosphoceramide. Ceramide-1-phosphate is an important lipid mediator in animal systems, so it will interesting to learn in the fullness of time whether the plant analogue has a related function.

The abstraction service I use has belatedly informed me that the January 2012 issue of the Journal of Psychopharmacology is devoted to the topic of “Endocannabinoids”. The articles now appear to be open access.

I wish all who read these notes good health and happiness for Christmas and the New Year.

Two important publications on ceramides caught my eye this week. These are vitally import lipids, both as precursors of all the complex sphingolipids and with essential biological activities in their own right. One of these papers deals with the functions of ceramides in the yeast Saccharomyces cerevisiae, widely used as a model organism (Montefusco, D.J. et al. Distinct signaling roles of ceramide species in yeast revealed through systematic perturbation and systems biology analyses. Science Signal., 6, rs14 (2013); DOI). The technicalities of the paper may only be of interest to the specialist, but one take-home message is important to all biochemists, i.e., that ceramide species with different N-acyl chains and sphingoid bases are involved in the regulation of different sets of functionally related genes. Thus ceramides with long-chain fatty acid constituents are required for different purposes from those with very-long-chain fatty acids, while those containing phytosphingosine have different functions from those containing sphinganine. It is also a useful reminder that there is an essential requirement for fully saturated fatty acids in tissues; they are not present simply for decoration or to provide specific physical properties.

I do not mean to suggest that physical properties are not important. For example, a new study of ceramide formation in cultured human embryonic kidney cells suggests that different molecular species of ceramide formed by the action of different ceramide synthases induce distinctive changes in the physical properties of membranes. It is proposed that this is “a likely molecular mechanism by which different acyl chain ceramides exert their specific biological actions” (Pinot, S.N. et al. Changes in membrane biophysical properties induced by sphingomyelinase depend on the sphingolipid N-acyl chain. J. Lipid Res., 55, 53-61 (2014); DOI).

I have had time to read a further article from one of the review series that I mentioned last week, dealing with the production of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in marine organisms (Gladyshev, M.I. et al. Production of EPA and DHA in aquatic ecosystems and their transfer to the land. Prostaglandins Other Lipid Mediators, 107, 117–126 (2013); DOI). The authors present a convincing case that marine microalgae are the major source of these fatty acids in the aquatic food chain, and thence become a major supplier directly and indirectly to terrestrial animals, including humans. It is humbling to think how dependent we may be on these microscopic organisms.

The oils and fats journal Grasas y Aceites published by the Instituto de la Grasa (CSIC), Sevilla, Spain has moved to a digital publication format and is now fully open access. Most of the more recent articles are in the English language. You can find it at grasasyaceites.revistas.csic.es/index.php/grasasyaceites.

The December issue of Biochimica et Biophysica Acta - General Subjects (Vol. 1830; Issue 12) is devoted to the topic of “Albumin research in the 21st century” (edited by T. Peters and A.J. Stewart). Albumin is an essential transport molecule for unesterified fatty acids and other lipid metabolites, including prostanoids, lysophospholipids, bile acids and anandamide, in blood, so the topic is an important one. Structure, binding properties and clinical applications are covered.

I am used to articles extolling the virtues of fish oils in the diet, so it was something of a surprise to find an article with a very different view point (Fenton, J.I. et al. Immunomodulation by dietary long chain omega-3 fatty acids and the potential for adverse health outcomes. Prostaglandins, Leukotrienes and Essential Fatty Acids, 89, 379–390 (2013); DOI). The suggestion is that “Recent studies of bacterial, viral, and fungal infections in animal models of infectious disease demonstrate that long-chain ω-3PUFA intake dampens immunity and alters pathogen clearance and can result in reduced survival.” It seems that the properties of these fatty acids that lead to the resolution of inflammation can impair the clearance of pathogens during serious infections. On the other hand, a sister journal carries a useful review on the beneficial properties of the resolvins (derived from DHA) in which it is stated that “Lipoxins and resolvins are safe and efficacious in treating human diseases” (Recchiuti, A. Resolvin D1 and its GPCRs in resolution circuits of inflammation. Prostaglandins Other Lipid Mediators, 107, 64–76 (2013); DOI). Perhaps the answer lies in the general nutritional advice – a little of what you fancy does you good. Taking extra may not confer additional benefits.

The latter article is published as part of conference proceedings, including several reviews that caught my eye. For example, a great deal of fascinating information is now being published on lysophospholipids, especially lysophosphatidic acid, which is an important lipid mediator and signalling molecule. On the other hand, I was less aware of important data on the biological activity of lysophosphatidylinositol (LPI). It seems that 2-arachidonoyl-LPI in particular interacts with a very specific receptor and may even be an endocannabinoid (Yamashita, A. et al. The actions and metabolism of lysophosphatidylinositol, an endogenous agonist for GPR55. Prostaglandins Other Lipid Mediators, 107, 103–116 (2013); DOI). Also, it is potentially a precursor for the endocannabinoid 2-arachidonoylglycerol.

November, 2013

Scottish thistle A paper with the technique “ultra-performance convergence chromatography” in the title sent me to the internet to discover what this was. It turns out that that this is simply supercritical fluid chromatography under a new name, albeit with significant technical improvements (Zhou, Q. et al. Chemical profiling of triacylglycerols and diacylglycerols in cow milk fat by ultra-performance convergence chromatography combined with a quadrupole time-of-flight mass spectrometry. Food Chem., 143, 199-204 (2014) – yes we are in 2014 already it seems; DOI). The separations described are indeed very good, but I suppose the re-naming of the technique is simply for commercial purposes. Supercritical fluid chromatography never really caught on for the analysis of lipids in spite of the potential advantages of being able to use carbon dioxide as the mobile phase. The methodology was at its best with triacylglycerols and I understand that it was used routinely in process control of infant formulations in industry, for example. However, with most other lipids it was necessary to add other solvents to the mobile phase, negating the benefits of the volatility of carbon dioxide. It will be interesting to see whether sufficient improvements have been made with the new instrumentation to influence lipid analysts to attempt other separations.

You might think that it is self-evident that lipid oxidation in tissues is a ‘bad thing’. However, a new review of the process in plants suggests that this may not be so, and that both lipid peroxidation and generation of reactive electrophile species can be of benefit to cells. It is suggested that these metabolites or 'phytoprostanes' reprogram gene expression and are involved in a number of signalling pathways. In particular they stimulate ‘the expression of genes encoding detoxification functions, cell cycle regulators, and chaperones’. It seems that these reactions are on a par with the functions of the jasmonates (see our webpage on plant oxylipins) (Farmer, E.E. and Mueller, M.J. ROS-mediated lipid peroxidation and RES-activated signalling. Annu. Rev. Plant Biol., 64, 429–450 (2013); DOI).

This should not be entirely surprising as the isoprostanes, i.e., prostanoids formed non-enzymically in animal tissues, are now believed to have distinct biological functions in normal physiology. Indeed, it has been proposed that during evolution in primitive cells, isoprostanes formed in the increasing aerobic conditions became a means of signalling the redox state of the cells and may have been retained as a back-up system to enzymic production.

Non-scientists may cringe at the thought of working on the components of urine, but it should be evident that it is in fact an invaluable biofluid that is easy to obtain in quantity. It is relatively sterile and lacks interfering proteins or bulk lipids. On the other hand, it does contain a number of lipids that can be useful diagnostic markers, including acylcarnitines, which can be an indicator of metabolic problems in the newborn, and isoprostanes, which are considered to be a marker for oxidative stress. A new open-access publication gives as comprehensive account of the constituents ’metabolome’) of urine as we are likely to get (Bouatra, S. and 18 others. The human urine metabolome. PLOS One, 8, e73076 (2013); DOI). The authors used a combination of chromatographic and spectroscopic techniques to identify 445 distinct metabolites in urine. However, an accompanying literature survey lists a further 2206 compounds.

As a service to the scientific community, the data have been assembled into an online database containing all known metabolites in human urine, their structures and concentrations, together with references to key publications. They are freely available at www.urinemetabolome.ca.

Cardiolipin is a unique lipid in many ways. For example, it is located only in mitochondria, where it is a key component of the oxidative phosphorylation system, and it has twice as many phosphate and fatty acid moieties as the conventional phospholipids. Also, depending on tissue, it has a restricted range of fatty acid components, resulting in a few relatively symmetrical molecular species. It has been accepted up till now that the two phosphate groups have very different acidities, with pK₁ = 2.8 and pK₂ = 7.5-9.5. A new study has come up with very different results, i.e., pK₁ = 2.15, similar to that of phosphoric acid, with pK₂ about one unit greater. The paper is open access (Olofsson, G. and Sparr, E. Ionization constants pK(a) of cardiolipin. PLOS One, 8, e73040 (2013); DOI). The data are important for understanding how cardiolipin interacts with enzymes and proteins in membranes to affect their biological functions.

The mechanism by which free fatty acids cross membranes into animal cells has long been a matter for debate, i.e., whether it is a simple diffusion process or whether an active transport system is involved. The evidence for the former is strengthened by a paper demonstrating that a candidate for an active transporter, a protein designate ‘CD36’, in fact promotes esterification, thereby reducing the cellular concentration of unesterified fatty acids and indirectly increasing flux across the plasma membrane by a passive process (Xu, S. et al. CD36 enhances fatty acid uptake by increasing the rate of intracellular esterification but not transport across the plasma membrane. Biochemistry, 52, 7254-7261 2013; DOI).

All biochemists will recognise the qualities of the Journal of Biological Chemistry. I have just noticed that they have a specific webpage – “Lipids at the JBC”, edited by George Carman - lipids.jbc.org/.

October, 2013

Scottish thistle When I was a post-doctoral fellow at the Hormel Institute nearly 50 years ago, one laboratory was filled by a counter-current distribution apparatus. It was an awesome sight in operation using large quantities of solvents to enable separations of fractions enriched in specific fatty acids on a scale suitable for nutritional experiments. I have never seen modern equipment in action, but I understand that it can sit handily on a bench top. Amongst numerous applications, it seems to be a mild and convenient method to obtain enrichment of minor fatty acids for further analysis by GC-MS, while operating on a greater scale than is possible with conventional HPLC equipment, for example. A number of interesting papers in which this apparatus has been utilized for detailed analyses of fatty acids have been published from the laboratory of Professor Walter Vetter in Germany, e.g. the most recent (Hammann, S. et al. Profiling the fatty acids from a strain of the microalgae Alexandrium tamarense by means of high-speed counter-current chromatography and gas chromatography coupled with mass spectrometry. J. Chromatogr. A, 1312, 93-103 (2013); DOI).

Last week in the UK, an eminent cardiologist wrote an piece in the British Medical Journal, which was widely publicized in our national press, to "bust the myth of the role of saturated fat in heart disease". Two days later the major food manufacturers gave a pledge to reduce the saturated fat content of their products, as part of a voluntary "responsibility deal" between industry and government (the sugar and salt contents are not affected). Should we care?

I would like to congratulate my colleague, friend and mentor, Professor Frank Gunstone, on the occasion of his 90th birthday. He is still actively writing and editing, although he is threatening to really retire this year.

After the Lipid Library, my favourite lipid-oriented website is Cyberlipid) maintained by Claude Leray in France. In particular, I frequently consult the section of the site titled ‘Descriptions’, where there is a wealth of basic information especially on the structures of unusual lipids.

One review to catch my eye this week is one dealing with ‘lipidic nanoparticles’ as carriers for anti-cancer drugs. These have low toxicity and enable controlled release of the drugs incorporated into the matrix (Mussi, S.V. and Torchilin, V.P. Recent trends in the use of lipidic nanoparticles as pharmaceutical carriers for cancer therapy and diagnostics. J. Materials Chem. B, 1, 5201-5209 (2013); DOI). By coincidence, I also came across an article in Science Daily News on the use of liposomes as a safe and effective way to introduce one specific anticancer drug that is otherwise toxic.

I suppose few of us have access to all the journals we would wish. My former employer permits me to access their library where they have contracts with the bigger publishers, but there are innumerable journals out of my reach. When a new review appears in any of these that might be of interest, I always have a quick look as many journals have an enlightened attitude of making some of these open access. One such is a recent review in the Journal of Biochemistry on polyphosphoinositides (Takasuga, S. and Sasaki, T. Phosphatidylinositol-3,5-bisphosphate: metabolism and physiological functions. J. Biochem., 154, 211-218 (2013); DOI).

We are getting used to seeing fascinating papers on the lipidomics of human tissues, and these are providing important new approaches to health or disease issues. There is also a great deal of fascinating, if less heralded, work on plant lipidomics. A new study on the lipidome of maize leaf has found innumerable associations with the genome as well as strong connections with agronomic traits (Riedelsheimer, C. et al. The maize leaf lipidome shows multilevel genetic control and high predictive value for agronomic traits. Scientific Rep., 3, 2479 (2013); DOI). The paper is open access.

I have just come across a paper dealing with the application of a new variant on the evaporative light-scattering detector to lipid analysis, the Nano Quantity Analyte Detector (NQAD™) (Beppu, F. et al. Quantification of triacylglycerol molecular species in cocoa butter using high-performance liquid chromatography equipped with nano quantity analyte detector. J. Oleo Sci., 62, 789-794 (2013); DOI). This employs a similar nebulization and evaporation phase to other ELSD, but the dry aerosol passes into a chamber where water vapour is condensed onto the particles so they increase in size to the point where individual particles can be counted. Thus, rather than measuring a cloud of particles, the instrument counts separate droplets. It is claimed that the sensitivity and linearity of the response are apparently greatly improved, and this paper (open access) appears to confirm this for one analytical problem at least.

A fascinating review on the biochemistry and function of lipids in mitochondria has just been published online first (Horvath, S.E. and Daum, G. Lipids of mitochondria. Prog. Lipid Res., 52, 590-614 (2013); DOI). Some of the key lipids, including phosphatidylglycerol and cardiolipin, can be synthesized in the organelle, while others such as phosphatidylcholine and phosphatidylserine have to be imported. In addition, their precise location in the inner and outer membranes are essential to their function. Cardiolipin is of course of crucial importance to the respiratory function of mitochondria.

Two reviews of analytical methodology from the journal Biomedical Chromatography have caught my eye this week. The first deals with the analysis of sterols other than cholesterol in plasma, including cholesterol precursors and metabolites and plant sterols (Andrade, I. et al. Advances in analytical methods to study cholesterol metabolism: the determination of serum noncholesterol sterols. Biomed. Chromatogr., 27, 1234-1242 (2013); DOI). I am not aware of an online source of mass spectra of sterols similar to the one we have on this website for fatty acids derivatives. We do have a few spectra of sterols here for reference, but it would be useful if a much more comprehensive selection were available somewhere.

The second review deals with the analysis of acylcarnitines (Mansour, F.R. et al. Separation of carnitine and acylcarnitines in biological samples: a review. Biomed. Chromatogr., 27, 1339-1353 (2013); DOI). The concentrations of these in biological fluids are invaluable markers for many metabolic disorders, including those of the brain and heart, together with diabetes. I had an interest in the analysis of these lipids many years ago before LC-MS techniques became available, but had little success mainly because of the zwitterionic nature of the molecules. They tended to co-elute with choline-containing lipids in many chromatographic systems. Modern mass spectrometric techniques appear to have solved the problem

I have been getting a little hot under the collar recently over simple nomenclature errors in publications, often in the titles. For example in my literature search this week, I found the term ‘sphingosine, which refers to a very specific sphingoid base, used as a generic term for a sphingolipid. In another paper, I found the term ‘stereospecific’ used in the title instead of ‘regiospecific’, when the two primary positions of triacylglycerols were not distinguished, and in yet another (in the body of the paper) the fatty acids of the ‘sn-1’ position were analysed when in fact it was again the combined sn-1/3 positions. Finally, I found a paper in which each of the terms ‘triacylglycerols, triacylglycerides and triglycerides’ were used in different parts of the abstract to denote the single lipid class.

While I am on my hobby horse, I may as well have another go at the use of the term HILIC or Hydrophilic Interaction Liquid Chromatography. Aside from the fact that such usage as ‘HILIC chromatography’ is redundant, the technique is used in many different ways with quite distinct chromatographic mechanisms. For example, I have seen it used for conventional silicic acid columns and with bonded diol or nitrile phases (‘adsorption chromatography’). It is also used with amide, amine and zwitterionic phases, where the mechanism of the separation is partly adsorption and partly ion-exchange. However, my main concern is reserved for manufacturers who simply label their columns as HILIC without giving any information on the chemical nature of the phase. Incidentally, amine-bonded phases are not new – I published my first paper using one such more than 30 years ago, and I was not the first. I can accept a term such as a ‘HILIC amide’ phase, also seen this week, if reluctantly.

I feel much better now I have all of this off my chest and I am ready for another short vacation!

September, 2013

Scottish thistle I admire the Journal of Lipid Research for making new articles available in manuscript form up to the date of publication and then fully open access after a year. Also, I like how they have thematic review series that appear over months, rather than as a special issue. For an editor, it means that timely contributions are not held back by tardy authors (I speak from bitter experience). A new series “Thematic Reviews on the Living History of Lipids” edited by A.H. Merrill is now promised, and this is one that I am sure I will enjoy. The manuscript of the editorial page lists “Lipid Hypothesis of Atherosclerosis”, phospholipids, eicosanoids, endocannabinoids, bile acids and sphingosines as the initial topics. There may be more to come later.

A new class of lipids has been found in animal tissues – a steroidal alkaloid, formed by enzymatic conjugation of 5,6α-epoxy-cholesterol and histamine. As this has anticancer activities, I am sure we will be hearing more about it in years to come (de Medina, P. et al. Dendrogenin A arises from cholesterol and histamine metabolism and shows cell differentiation and anti-tumour properties. Nature Commun., 4, 1840 (2013); DOI). Happily, the paper is open access.

The November issue of the journal Biochimica et Biophysica Acta - Molecular Cell Research is devoted to the topic of “Functional and structural diversity of endoplasmic reticulum” (edited by Maya Schuldiner and Blanche Schwappach). It contains several papers of direct interest to lipid biochemists, including reviews dealing with phospholipids, sphingolipids and glycosylphosphatidylinositol-anchored proteins.

The October issue of the journal Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids is concerned with the topic of “Lipid Metabolism in Cancer” (edited by B.F. Cravatt and D.K. Nomura). I will not be delving deeply into this as it is more the realm of the specialist, but a brief perusal of the abstracts has been sufficient to show that lipids are involved in a host of different ways in the progression of cancer. Often it appears that disturbances in lipid metabolism are merely a symptom of the disease, but there are other examples where lipids have a more direct role sometimes in promoting and in other instances in inhibiting the proliferation of cancer cells.

The phosphatidylinositol phosphates have a key role in the functioning of all eukaryotic cells. However, there is a major divergence between plants and animals in which pathways are present and how they operate pathways. A new review demonstrates this for plant systems (Heilmann, M. and Heilmann, I. Arranged marriage in lipid signalling? The limited choices of PtdIns(4,5)P-2 in finding the right partner. Plant Biol., 15, 789-797 (2013); DOI).

Nearly half the world’s supply of fish is now produced by aquaculture. A newly published paper in Lipids (Watson, A.M. et al. Taurine supplementation of plant derived protein and n-3 fatty acids are critical for optimal growth and development of cobia, Rachycentron canadum. Lipids, 48, 899-913 (2013); DOI) has attracted the interest of the popular scientific press and the web site Science Daily News especially. The authors demonstrate that fish produced by aquaculture methods can thrive on a vegetable-based diet, provided that it contains sufficient taurine and essential fatty acids. At present, it takes the meal and oil from 5 Kg of wild fish to produce 1 Kg of cultivated fish, and the hope is that the new diets can reduce this requirement and so help to preserve wild fish stocks and hopefully provide cleaner fish with lower levels of PCBs and mercury for consumers. It will be interesting to see whether the work can be extended to salmon and other species with which consumers are more familiar.

The membranes of cell organelles contain a wide range of lipids in the form of countless molecular species. These lipids are essential for the structural integrity of cells, but they are also intimately involved in the functions of membrane proteins. To quote from the abstract of a new review article – “Even subtle changes in lipid composition can have a tremendous impact on membrane properties and the processes occurring within them.” In order to understand the relationships between lipid composition and function, the authors provide a cogent argument that only mass spectrometry-based lipidomics can provide the required information (Klose, C. et al. Organellar lipidomics - background and perspectives. Curr. Opin. Cell Biol., 25, 406-413 (2013); DOI).

Modern mass spectrometry systems are enormously powerful tools for the analysis of lipids. However, a major drawback for newcomers to the technique is the accessibility and specificity of the software essential if data handling is not to become a mind-numbing chore. A new library of mass spectral data has now been made freely available that includes over 200,000 spectra and is compatible with 40 different types of mass spectrometer. I must praise the altruism of the authors (Kind, T. et al. LipidBlast in silico tandem mass spectrometry database for lipid identification. Nature Methods, 10, 755-758 (2013); DOI).

One of my hobby horses is the excessive use of adjectives or nouns used adjectivally to qualify a single noun in the title of a paper. My record reported last year was 14. It has now been raised to 15 (DOI).

To quote from a new review – “phosphoinositides (PIs) make up only a small fraction of cellular phospholipids, yet they control almost all aspects of a cell's life and death”. I am still waiting for full access to this, but it looks very worthwhile (Balla, T. Phosphoinositides: tiny lipids with giant impact on cell regulation. Physiol. Rev., 93, 1019-1137 (2013); DOI). Another medically orientated review to catch my eye is in an open access journal (Galadari, S. et al. Role of ceramide in diabetes mellitus: evidence and mechanisms. Lipids Health Disease, 12, 98 (2013); DOI).

August, 2013

Scottish thistle If you consult the biochemistry text books of about 10 years ago, you will find a short discussion of the nature and biosynthesis of the bile acids together with their role in aiding digestion and that is probably all. However, in recent years it has also become apparent that they have important roles in the regulation of gene expression and cellular function by serving as ligands for several nuclear receptors. With this has come an understanding of the mechanism of the enterohepatic circulation, by means of which bile acids are recycled, and its effect on cholesterol homeostasis. A new review discusses the topic (Zwicker, B.L. and Agellon, L.B. Transport and biological activities of bile acids. Int. J. Biochem. Cell Biol., 45, 1389-1398 (2013); DOI).

Unfortunately, the U.K. has one of the worst reputations in Europe for obesity, and it is a major problem in most other developed countries. I got a glimpse of this among the customers of a fast-food restaurant to which I took my grandchildren last week. It is a major risk factor for many common medical conditions, including Type 2 diabetes, cardiovascular disease and even some cancers. A number of research groups are exploring the potential of brown fat to alleviate this condition via its capacity to dissipate energy and regulate triacylglycerol and glucose metabolism. A new review discusses the potential for therapeutic intervention with this tissue (Schulz, T.J. and Tseng, Y.H. Brown adipose tissue: development, metabolism and beyond. Biochem. J., 453, 167-178 (2013); DOI).

Last week, I described how one of our national newspapers gave a full front-page spread to the effects of fish oils on arthritis. Today, the same newspaper has given similar publicity to the effects of broccoli on the disease. Regretfully, fish oil and broccoli does not seem to be a very appealing culinary combination.

Papers on docosahexaenoic acid have caught my eye this week. In particular, I regret to say that anything that relates to age and mental decline is certain to be of interest to me (though hopefully not of immediate concern). A new review considers this aspect especially (Denis, I. et al. Omega-3 fatty acids and brain resistance to ageing and stress: Body of evidence and possible mechanisms. Ageing Res. Rev., 12, 579-594 (2013); DOI). An adequate intake of DHA does indeed appear to be helpful, and thankfully I have always enjoyed fish in my diet. A second paper suggests that DHA supplementation confers long-term benefits in children (Colombo, J. et al. Long-term effects of LCPUFA supplementation on childhood cognitive outcomes. Am. J. Clin. Nutr., 98, 403-412 (2013); DOI). A third study made the front page of one of our national tabloid newspapers in the UK, though I have seen no further details of the source. It is claimed that dietary fish oils halve the risk of arthritis in the elderly.

Lipid mediators have been a recurrent theme of mine in recent weeks. A new paper (open access) suggests that the concentration of 13-hydroxy-ocadecenoate, and not other lipid metabolites, is strongly correlated with the progression of breast cancer (O'Flaherty, J.T. et al. Fatty acid metabolites in rapidly proliferating breast cancer. PLOS One, 8, e63076 (2013); DOI).

The latest paper to cross my desk on detailed analysis of lipid mediators has examined the concentrations of different components in mice infected with influenza (Tam, V.C. et al. Lipidomic profiling of influenza infection identifies mediators that induce and resolve inflammation. Cell, 154, 213-227 (2013); DOI). The results indicate that metabolites produced by 5-lipoxygenase are found in the “pathogenic phase of the infection, whereas 12/15-lipoxygenase metabolites were associated with the resolution phase”. Perhaps more surprisingly, the ratio of two C₁₈ components 13- and 9-hydroxyoctadecadienoic acid were important markers for immune status during infection.

When the charged-aerosol detector for HPLC of lipids first became available, it appeared to have the potential to solve many of the problems associated with the evaporative light scattering detector, especially the non-linear response. However, some of the first results published appeared to show noisy base-lines due to minor ionic impurities in the mobile phase. Two recent publications seem to demonstrate that the problems have been overcome (Khoomrung, S. et al. Rapid quantification of yeast lipid using microwave-assisted total lipid extraction and HPLC-CAD. Anal. Chem., 85, 4912-4919 (2013); DOI) (Damnjanovic, J. et al. Simple and efficient profiling of phospholipids in phospholipase D-modified soy lecithin by HPLC with charged aerosol detection. J. Am. Oil Chem. Soc., 90, 951-957 (2013); DOI). Indeed in both of these papers, the first of which is open access, ionic species form an essential component of the mobile phase. I will await further developments with interest.

Last week, I pointed to a paper in which the lipid mediators in adipose tissue had been measured. This week, I have found a fascinating paper on the presence of such lipids in human milk (Weiss, G.A. et al. High levels of anti-inflammatory and pro-resolving lipid mediators lipoxins and resolvins and declining docosahexaenoic acid levels in human milk during the first month of lactation. Lipids in Health Disease, 12, 89 (2013); DOI). To quote from the conclusions – “the high content of anti-inflammatory and pro-resolving lipid mediators and their precursors may indicate their role in neonatal immunity and may be one of the reasons for the advantage of human milk over infant formula.” As a mere male, I couldn’t possibly comment. By the way, the paper is open access.

I can recommend an excellent review on the analysis of trans fatty acids that has just been published (Tyburczy, C. et al. Determination of trans fat in edible oils: current official methods and overview of recent developments. Anal. Bioanal. Chem., 405, 5759-5772 (2013); DOI). I would take issue with the authors on one point only in that they cast doubt on the value of silver ion chromatography for this purpose, suggesting that “the microgram quantities obtained are particularly susceptible to sample loss or oxidation”. I do not believe that this need be a serious problem with monoenes. My first paper on a method of this kind was published 40 years ago, and I have not noticed such a problem in the intervening years.

The strangest lipid story of this and most other weeks was reported in many British newspapers yesterday, i.e., the discovery of a “fat berg the size of London bus” in the London sewers. Apparently, this 20-ton deposit resulted from the accumulation of cooking fats dumped down the drains over a period of many years.

In recent years, the methodology associated with the techniques of lipidology has given rise to a large number of reviews in the literature. It is a change to find one that deals with the results rather than the methodology (Loizides-Mangold, U. On the future of mass-spectrometry-based lipidomics. FEBS J., 280, 2817-2829 (2013); DOI). The author discusses the great complexity of lipids in tissues, and how this varies between organelles. Understanding the requirements for this complexity and how it is maintained are enormous challenges for the future.

Another paper that looks fascinating though I don’t yet have access to it is one dealing with eicosanoids and docosanoids in adipose tissue (Claria, J. et al. Diversity of lipid mediators in human adipose tissue depots. Am. J. Physiol.-Cell Physiol., 304, C1141-C1149 (2013); DOI). It is only in the last decade or so that it has been recognised that adipose tissue is more than simply an energy store. It seems that it contains a complex and highly diverse range of eicosanoids, including prostaglandins, hydroxy-eicosatetraenes and leukotrienes, and pro-resolving mediators such as the resolvins, protectins and lipoxins. The concentrations vary in different fat locations and with body mass index. Again, unravelling the reasons for this complexity will be a fascination challenge.

July, 2013

Scottish thistle It was perhaps inevitable, but it looks as if lipid analysts are about to be replaced by robots. A new paper (open access) demonstrates a robotic method for profiling the fatty acid composition of the fatty acids in plasma. It combines two robotic steps to perform lipid extraction, phospholipid isolation, hydrolysis and derivatization to fatty-acid methyl esters, and on-line analysis by gas chromatography. As a first step it has been applied to a mere 850 samples to test the methodology, with another 24,000 to go! (Wang, L.Y. et al. Development and validation of a robust automated analysis of plasma phospholipid fatty acids for metabolic phenotyping of large epidemiological studies. Genome Med., 5, 39 (2013); DOI).

It has been known for some years that apoprotein A1, a key component of the high-density lipoproteins, has anti-inflammatory properties and is protective against heart disease. A new paper now demonstrates that it also has anti-cancer properties in animal studies in vivo (Zamanian-Daryoush, M. et al. Cardioprotective protein may also work as an anti-tumor agent?: The cardioprotective protein apolipoprotein A1 promotes potent anti-tumorigenic effects. J. Biol. Chem., 288, 21237–21252 (2013); DOI).

I was sorry to learn of the death of Bob Ackman, who I first met about 30 years ago and who became a good friend. I was privileged to visit his lab and home in Halifax. He became a regular correspondent and packages of cuttings – scientific or simply cartoons that he had enjoyed - used to arrive in my post at regular intervals. His contribution to our knowledge of fish oils was immense, and it would be difficult to write any paper dealing with marine lipids without citing his publications.

The jasmonates are 12-carbon cyclic fatty acids and their derivatives produced from α-linolenic acid, which have important signalling functions in plants, but especially in plant stress responses, growth and development. The key metabolite now known to be jasmonoyl-isoleucine, as it is the only jasmonate known with certainty to be active at the molecular level via an identified receptor. In their chemical structures, the jasmonates have a marked similarity to the prostaglandins, which are such important animal metabolites, surely as a result of parallel evolution. Two recent reviews embrace the biochemistry and function of these fascinating lipids, and happily both are open access (Koo, A.J.K. and Howe, G.A. Catabolism and deactivation of the lipid-derived hormone jasmonoyl-isoleucine. Front. Plant Sci., 3, 19 (2012); DOI; Wasternack, C. and Hause, B. Jasmonates: biosynthesis, perception, signal transduction and action in plant stress response, growth and development. An update to the 2007 review in Annals of Botany. Annals Botany, 111, 1021-1058 (2013); DOI).

Fifty years ago column chromatography on diethylaminoethyl (DEAE) cellulose was considered to be one of the best procedures available for preparative scale separations of polar lipids especially, and I made extensive use of it in my early career. The principle is largely ion-exchange but with some adsorption effects. I expected that it would be superseded by newer polymeric materials, perhaps of the Sephadex^TM type, but this never appeared to happen. It is years since I last noticed a published application, though I have tried to ensure that the technique is not forgotten through my book Lipid Analysis (Christie & Han). This week at long last I encountered an application for the separation of a complex glycolipid fraction from phospholipids and lipophilic pigments prior to further analysis (Antonopoulos, E. et al. Fractionation and purification of membrane lipids from the archaeon Thermoplasma acidophilum DSM 1728/10217. Sep. Pur. Technol., 110, 119-126 (2013); DOI).

Lysophosphatidic acid has long been considered to be a useful marker for ovarian cancer. A new paper suggests that it also is involved in hepatocellular carcinoma, and indeed that specific molecular species are the key (Skill, N.J. et al. Lysophospholipid variants in hepatocellular carcinoma. J. Surgical Res., 182, 241-249 (2013); DOI). Once more this is an advance made possible only by the application of modern mass spectrometric methods.

Hot on the heels of my comments on plant sphingolipids, a new review outlines their biochemistry (Markham, J.E. et al. Plant sphingolipids: function follows form. Curr. Opin. Plant Biol., 16, 350-357 (2013); DOI). It is evident that great strides have been made in our knowledge of how the structures of the fatty acid and long-chain bases in sphingolipids affect the functions of the latter in plants. However, relatively little is yet known of the functional significance of the polar head groups of the more complex sphingolipids, especially of the glycosyl inositolphosphoceramides mentioned in my last blog.

A few years ago I was privileged to receive an invitation to a symposium on Barth syndrome, a genetic disease involving a defect in the metabolism of cardiolipin in mitochondria. It was impressive to see the courage of the boys affected by the syndrome, who in effect were guinea pigs for unproven treatments. The girls in the affected families, who were potential carriers of the defective genes, knew that as they grew older they would be faced with the difficult dilemmas already encountered by their parents. The parents and children came to mind with the news that the U.K. government is considering allowing an IVF treatment that might eliminate mitochondrial diseases of all kinds. It is controversial in that three donors are involved. As I understand it, the nuclei of a fertilized egg is transferred to an egg containing only healthy mitochondria from a third person. Of course, it is coming under fire in some quarters as being ‘unnatural’. The nay-sayers should meet the brave families dealing with Barth syndrome.

June, 2013

Scottish thistle I have heard phospholipids called many things during my career, but it is something of a novelty to see them described as ‘hormones’, as in a recent review (Musille, P.M. et al. Phospholipid-driven gene regulation. FEBS Letts, 587, 1238-1246 (2013); DOI). It has long been known that hydrolysis products of phospholipids, such as diacylglycerols or inositol phosphates, act as second messengers in signalling cascades. To quote from the abstract – “Recent work has shown that intact phospholipids act as signalling molecules in their own right by modulating the activity of nuclear hormone transcription factors responsible for tuning genes involved in metabolism, lipid flux, steroid synthesis and inflammation. As such, phospholipids have been classified as novel hormones.”

For nearly 40 years after the basic work of H.E. Carter in the 1960s, the ‘phytosphingoglycolipids’ now better termed ‘glycosyl inositol phosphoceramides’ were neglected in higher plants, until it was recognized relatively recently that they made up a much greater proportion of the membrane lipids than had been supposed. Two years ago, I highlighted an important paper in this blog on the analysis of these compounds by mass spectrometry. A new paper has just appeared describing alternative mass spectrometric methods of analysis (Blaas, N. and Humpf, H.U. Structural profiling and quantitation of glycosyl inositol phosphoceramides in plants with Fourier transform mass spectrometry. J. Agric. Food Chem., 61, 4257-4269 (2013); DOI). Improved analytical methods are often the precursor to new biological findings, and I trust that we will be reading more about these fascinating lipids in the years ahead.

A new paper poses an interesting question (Brouwer, I.A. et al. Trans fatty acids and cardiovascular health: research completed? Eur. J. Clin. Nutr., 67, 541-547 (2013); DOI). One statement is absolutely unequivocal – “the detrimental effects of industrial trans fatty acids on heart health are beyond dispute.” On the other hand, the authors hedge on the effects of trans fatty acids in naturally occurring ruminant fats, such as those in milk and beef, and on the safety of conjugated linoleic acid (CLA). I drink milk and I enjoy beef and lamb, and will continue to do so in moderation, but I have often wondered about claims from some scientists (not the authors of this paper) that trans fatty acids from these sources are safer than industrial hydrogenation products. To me it seems like wishful thinking. While I fear that it might be the product of extensive lobbying by farming interests, I suspect that it is more likely to be a simplistic and unrealistic view that ‘natural’ must be good, industry ‘bad’.

The July issue of the Journal of Lipid Research contains a promised thematic review series on the fat soluble Vitamin A. There are four major articles and an editorial, all well worth reading.

For much of my research career, I had an interest in the analysis of molecular species of lipids. In the early days especially, it was difficult to convince others that this was more than an academic exercise. Nowadays, this would not be a problem and indeed most modern mass spectrometric methods are designed specifically to determine molecular species as the first step in lipid analyses. It would be easy to list any number of instances where specific molecular species of lipids have biological importance. The latest example to come to my notice concerns macrophages subjected to inflammatory stimuli, when phosphatidylinositol containing two molecules of arachidonate is produced. Biosynthesis involves sequential acylation of positions sn-2 and then sn-1 by remodelling of an existing phosphatidylinositol molecule. There is evidence that is a novel bioactive phospholipid regulating innate immune responses in these cells (Gil-de-Gomez, L. et al. A phosphatidylinositol species acutely generated by activated macrophages regulates innate immune responses. J. Immunol., 190, 5169-5177 (2013); DOI).

The journal Current Organic Chemistry (Volume 17, Number 8, April 2013) contains a number of review articles under the theme of 'Therapeutic Agents of Lipids and Fatty Acids'. There is a particular emphasis on ether lipids.

The journal Free Radical Biology and Medicine has a special issue (Volume 59, Pages 1-108, June 2013) devoted to the topic of “Methods in Lipid Oxidation” (edited by Henry Forman and Kevin Moore). I found it of special interest in that some key articles deal with analysis of the less common oxidation products, including nitro fatty acids, chloro lipids and aldehydes, which are of great biological importance.

There was a time when sphingomyelin was looked upon as simple an analogue of phosphatidylcholine, which was more resistant to lipases. For example, the sphingomyelin replaces phosphatidylcholine entirely in the membranes of the erythrocytes of sheep and other ruminant animals. Of course, it is now realised that the two lipids are very different in both their physical and biological properties, and that sphingomyelin especially has a highly distinctive role in membranes in that it interacts with cholesterol to form raft domains. These control innumerable signalling functions in cells. Two recent review on sphingomyelin have come to my attention. The first fortuitously is open access and deals with the role of sphingomyelin in lipoproteins (Martinez-Beamonte, R. et al. Sphingomyelin in high-density lipoproteins: structural role and biological function. Int. J. Mol. Sci., 14, 7716-7741 (2013); DOI). It appears that increased levels of HDL sphingomyelin are an inverse risk factor for coronary heart disease. However, increased levels of sphingomyelin in whole plasma increase the risk of cardiovascular disease. The second review, just released online, deals with the biological properties of sphingomyelin in general (Slotte, P.J. Biological functions of sphingomyelins. Prog. Lipid Res., 52, 424-437 (2013); DOI).

May, 2013

Scottish thistle If I had been asked to cite the first paper to show that lipids had functions other than as a source of energy, I would probably have listed the classic work of Burr and Burr from the 1920s on essential fatty acids (see Smith, W. and Mukhopadhyay, R. Essential Fatty Acids: The Work of George and Mildred Burr. J. Biol. Chem., 287, 35439-35441 (2012); DOI. However, an editorial in the Journal of Lipid Research (Blaner, W.S. The fat-soluble vitamins 100 years later: where are we now?), just available in manuscript form, suggests that the first to provide evidence of the fat-soluble vitamins 100 years ago may be due this honour (McCollum, E.V. and Davis. M. The necessity of certain lipins in the diet during growth. J. Biol. Chem., 15, 167-175 (1913)). The journal has a series of thematic reviews on the fat-soluble vitamins in the pipeline – something for which to look forward when I return from my annual vacation.

As far as I can ascertain, the first mention of sphingosine-1-phosphate in the scientific literature was in 1970 by Wilhelm Stoffel and colleagues. At the time, this appears to have attracted little notice and another 25 years or so were to pass before the scientific community began to give due attention to this key molecule, which is now understood to have vital roles in health and disease in that it affects cardiac function, vascular development, immune cell function, inflammation, cancer and Alzheimer’s disease. Google scholar suggests that there were 3,600 publications touching on this lipid last year. It is transported in the blood stream in complexation with apolipoprotein M in the HDL, and this complex activates a specific receptor S1P₁. Their combined interactions are now seen to be of relevance to atherosclerosis and perhaps other diseases. A new review discusses this aspect of the topic (Arkensteijn, B.W.C. et al. The apolipoprotein M-sphingosine-1-phosphate axis: biological relevance in lipoprotein metabolism, lipid disorders and atherosclerosis. Int. J. Mol. Sci., 14, 4419-4431 (2013); DOI).

The world is such a beautiful place that I have difficulty in understanding how anyone would wish to change their perception of it with drugs. Indeed, I sometimes get the impression from the popular news media that I am one of the few people left in the world who has not tried cannabis. This exerts its physiological functions by activating specific receptors in cells, the true function of which are important in many aspects of human physiology and are relevant to many disease states. The real endogenous ligands are lipids, and they have been termed ‘endogenous cannabinoids’ or ‘endocannabinoids’, e.g. anandamide and 2-arachidonoylglycerol. As we know more and more about the biochemistry and functions of specific lipids, reviews dealing with them tend to become more specialized and restricted to specific aspects. I find it helpful, therefore, when a more general overview is published that attempts to put developments into a proper perspective. It is not an easy read for non-biochemists, but I can recommend one such (Fonseca, B.M. et al. Endogenous cannabinoids revisited: A biochemistry perspective. Prostaglandins Other Lipid Mediators, 102/103, 13-30 (2013); DOI).

I have belatedly become aware of a special issue of a new journal Metabolites, the January issue (2012) of which is devoted to the topic of "Lipidomics". There are a number of interesting articles including one on the analysis of glycolipids, and another on the technology of modern mass spectrometric methods. All of these have the additional virtue of being open access.

Another useful set of reviews has been published in the journal Molecular and Cellular Endocrinology (Volume 368, Issues 1–2, Pages 1-128 (10 April 2013)) and deals with the topic of “Nuclear Receptors, Bile Acids and Cholesterol Homeostasis” (edited by Kristina Schoonjans).

I have a particular interest nowadays in the biological functions of lipids, but equally interesting is how natural lipids are being used in industrial/commercial applications of various kinds, especially in health products via the pharmaceutical industry. Two recent reviews in the journal Biotechnology Advances have caught my eye. The most recent deals with the potential of bacterial lipopeptides in the control of infection and it seems that at least four have reached commercial status. Others appear to have great promise against the antibiotic resistant strains of bacteria, which are so troublesome in our hospitals. Other lipopeptides have applications as surfactants and emulsifiers, and even in cosmetics as anti-wrinkle agents (Mandal, S.M. et al. Lipopeptides in microbial infection control: Scope and reality for industry. Biotechnol. Adv., 31, 338-345 (2013); DOI).

The second review in this journal, published towards the end of last year, deals with the industrial uses of products of lipoxygenases. It seems that “animal lipoxin LXA4, plant jasmonic acids, plant green leaf volatiles, and bacterial lactones have been used as anti-inflammatory agents, anti-pest agents, flavors, and food additives, respectively” (Joo, Y.-C. and Oh, D.-K. Lipoxygenases: Potential starting biocatalysts for the synthesis of signaling compounds. Biotechnol. Adv., 30, 1524-1532 (2012); DOI).

April, 2013

Scottish thistle As a school boy, I never appreciated my French teacher – Monsieur Smith (his name corrupted by his pupils to ‘Messerschmitt’ and then simply ‘Mesh’ out of his hearing), but I was grateful to him in later years on my occasional visits to France or when I read a scientific paper in French (reading is infinitely easier than speaking the language for me now). As a Francophone, I have mixed feelings about rarely using these waning skills as so many important French journals now publish in English only, not least Biochimie (Société française de biochimie et biologie moléculaire). The March issue of this journal has an important series of review articles on ‘Oxysterols and Related Sterols in Chemistry, Biology and Medicine’ (edited by Luigi Iuliano and Gérard Lizard – Biochimie, 95, Issue 3, 445-640 (March 2013)). I suppose that we have to be grateful that we have a 'Lingua Franca' for science and that it is English (or American).

The May issue of Biochim. Biophys. Acta - Molecular and Cell Biology of Lipids (Vol. 1831, Issue 5, Pages 895-1008 (May 2013)) is devoted solely to the topic of ‘Brown and White Fat: From Signaling to Disease’ (edited by S. Herzig and C. Wolfrum).

A substantial biography of the late A.T. (Tony) James, who amongst many other achievements in lipid biochemistry was the inventor of gas chromatography, has been published by Mike Gurr (Biogr. Mems. Fell. R. Soc., 58, 129-150 (2012); DOI).

The O-acylated proteolipids have been on my radar for some time, but two recent reviews have raised their profile. The best known is probably ghrelin, which is of particular importance as a hunger-stimulating hormone produced in the human stomach and pancreas, increasing food intake and adiposity. It can be octanoylated at a serine residue and this is essential for binding to its specific receptor. The enzyme that catalyses octanoylation is now a target for pharmaceutical intervention for treatment of the metabolic syndrome. (Romero, A. et al. GOAT: the master switch for the ghrelin system? Eur. J. Endocrinol., 163, 1-8 (2010); DOI).

Secondly, the family of Wnt proteins are central mediators of animal development, influencing cell proliferation, differentiation and migration. They are S-palmitoylated on a conserved cysteine residue, but they have a second unusual O-acyl modification with palmitoleic acid at a conserved serine residue. O-Acylation requires an acyltransferase termed 'Porcupine', which has become a high-priority target for an anticancer drug (Ke, J. et al. Lipid modification in Wnt structure and function. Current Opinion in Lipidology, 24, 129-133 (2013); DOI). I am intrigued as to whether this highly specific function of palmitoleic acid might be related to its role as a lipokine.

The journal CNS & Neurological Disorders - Drug Targets has a new issue devoted largely to the subject of “Palmitoylethanolamide: Biochemistry, Pharmacology and Therapeutic Use of a Pleiotropic Anti-Inflammatory Lipid Mediator”. This issue is open access.

I was fascinated by the title of a new paper in the Journal of Lipid Research (Chaitidis, P. et al. Lipoxygenase pathways in Homo neanderthalensis: functional comparison with Homo sapiens isoforms. J. Lipid Res., 54, 1397-1409 (2013); DOI). It is astonishing that we can now study lipid biochemistry in a species that has been extinct for 40,000 years.

The contribution of Margaret Hilda Roberts to lipid chemistry is not widely recognized, probably because she is a co-author of only one scientific paper (Jellinek, H.H.G. and Roberts, M.H. The saponification of α-monostearin in a monolayer. J. Sci. Food Agric., 2, 391–394 (1951); DOI). Her chemistry career was short and she left it to take a second degree in law before entering politics. She is better known under her married name of Margaret Thatcher. As such she became an iconic figure in the United Kingdom as our first woman Prime Minister and the longest serving one in the 20^th century. She was probably our most controversial politician also, and there are many who wish she had stuck to lipid chemistry. Whatever our political convictions, I suspect the world is poorer without her.

A new publication available as yet only in manuscript form suggests a short-hand nomenclature for lipids (Liebisch, G. et al. Shorthand notation for lipid structures derived from mass spectrometry. J. Lipid Res., in press. DOI). I believe that abbreviations and acronyms are grossly over-used in the scientific literature; they are a convenience for authors but simply a nuisance for readers. Nevertheless, there are occasions when they are useful, so if they must be used they should at least be standardized. One virtue of those proposed here is that they are simple, PC for phosphatidylcholine, for example, unlike those recommended in an early LIPID MAPS publication. One quibble I do have with the list is that it ignores the common plant lipids.

Shorthand nomenclature for fatty acids is confusing and inconsistent. A correspondent has recently reminded me that the shorthand nomenclature for linoleic acid is ‘18:2’ not ‘C18:2’, and I could add that the IUPAC-IUB recommendation is for ‘18:2(n-6)’ not ‘18:2n-6’, as are frequently found in journals. You will also find in the literature 9c,12c-18:2, Δ^9,12-18:2 and 18:2(9Z,12Z) (and probably more). The shorthand nomenclatures in common use for branched-chain fatty acids can even lead to errors in interpretation. It is time that international bodies looked again at these questions and I trust that they will consult more widely than the private consortia appear to have done. I am not hopeful as the last time I looked, the IUPAC web page dealing with lipid nomenclature had misinterpreted its own conclusions.

I am a firm believer in the open access movement for scientific publication, and I am grateful to those journals that may not be fully open but permit access a year or two after formal publication. It is distressing to read that fraudsters are getting into the act with bogus journals and scientific meetings, designed simply to fleece authors. The New York Times has a recent piece on the topic.

I have been reading a fascinating review on phosphatidylethanolamine (Vance, J.E. and Tasseva, G. Formation and function of phosphatidylserine and phosphatidylethanolamine in mammalian cells. Biochim. Biophys. Acta, 1831, 543-554 (2013); DOI). The modern science apart, I was entertained by a comment in the introductory section regarding the discovery of this lipid in 1884 by Ludwig Thudichum. It appears that during his lifetime his work was considered “relatively insignificant,” according to Thudichum's obituaries in Nature [volume 64, page 527 (1901)] and “The Times” of London (Sept. 10, 1901). The latter article stated that “the knowledge yielded by these researches was hardly commensurate with the time and cost at which it was obtained.”" The authors comment that “Unfortunately, similar sentiments are even today often applied to basic research”. This was certainly true in regard to lipids in general during the last century, when lipid science was often poorly taught in Universities. Thankfully, the true relevance of lipids to human health and well-being is now being recognized.

As an example, the most recent evidence for the importance of omega-3 fatty acids in human nutrition is the effects of epoxy-docosapentaenoic acid (a metabolite of DHA) on cancer reported in Science Daily News.

March, 2013

Scottish thistle How the science of lipidomics impinges on disease states is becoming a recurrent theme in these notes, and a new review offers an interesting perspective on the subject (Tucker, S.C. and Honn, K.V. Emerging targets in lipid-based therapy. Biochem. Pharmacol., 85, 673-688 (2013); DOI). It seems that a number of enzymes, accessory proteins and receptor molecules involved in lipid metabolism are now targets for therapeutic intervention. In addition, a number of lipid species are considered biomarkers for various disease states.

Similarly, the lipids of lung surfactant are important for health and disease, and the detailed molecular structures of the lipids and their biosynthesis and metabolism are under intensive scrutiny. This is also the topic of a new review (Goss, V. et al. Regulation of lung surfactant phospholipid synthesis and metabolism. Biochim. Biophys. Acta, 1831, 448-458 (2013); DOI).

Occasionally, I find reports of some unusual uses for lipids and a recent publication discusses the use of lysophosphatidylethanolamine in a number of horticultural applications. Apparently, when applied exogenously, the claimed “benefits include delayed leaf senescence, stimulation of ripening in table grape, acceleration of color development and extension of shelf-life in cranberry and tomato, and increased vase life of cut flowers”. The mechanism for these effect seems to be obscure as does the role of this lipid in vivo in plants (Amaro, A.L. and Almeida, D.P.F. Lysophosphatidylethanolamine effects on horticultural commodities: A review. Postharvest Biol. Technol., 78, 92-102 (2013); DOI).

The journal Current Opinion in Clinical Nutrition and Metabolic Care (Vol. 16:2) contains eight review articles on the theme of “Lipid metabolism and therapy” (edited by Philip C. Calder and Richard J. Deckelbaum). The main thrust of the articles concerns the effects of omega-3 fatty acids in various disease states.

Defects in lipid metabolism are implicated in Alzheimer’s disease and this is the subject of a new review (open access); it appears that much of the evidence comes from recent lipidomic studies (Wood, P.L. Lipidomics of Alzheimer's disease: current status. Alzheimers Res. Therapy, 4, 5 (2012); DOI). An isoform of apolipoprotein E is a major risk factor, but substantial deficits in brain structural glycerophospholipids and sphingolipids have also been detected together with effects on signalling molecules derived from these.

There is an intriguing report that N-acylethanolamines, including the endocannabinoids, exist in plasma and erythrocytes in esterified form, i.e., the free hydroxyl group as well as the amine moiety is esterified (Balvers, M.G.J. et al. Liquid chromatography-tandem mass spectrometry analysis of free and esterified fatty acid N-acyl ethanolamines in plasma and blood cells. Anal. Biochem., 434, 275-283 (2013); DOI). So far the evidence is indirect, but it will be interesting to learn whether these compounds are inert storage or transport forms, or whether they have biological properties in their own right.

The latest news on fish oils continues to be good for consumers. It seems the docosahexaenoic acid (DHA) interacts very specifically with ion channels with beneficial effects on blood pressure and the cardiovascular system. There is a popular account here..

In 2011, 20 substantial review articles were published under the title ‘The Biology of Lipids’ (edited by Kai Simons) as part of the Cold Spring Harbor Perspectives in Biology series. These have now been made freely available online to all readers.

The Biochemical Society Transactions (Vol. 41 Part 1 of 2013) contains a number of articles dealing with proteolipids or more specifically the theme of “Regulation of protein trafficking and function by palmitoylation” (edited by Luke Chamberlain and Tony Magee).

The term ‘lipid rafts’ is used to describe ordered structures in biological membranes arising from lateral segregation of sphingolipids and cholesterol. These attract specific proteins and other signalling molecules with profound effects on cell biology. I can recommend a new open access review, which summarises current knowledge (Sonnino, S. and Prinetti, A. Membrane domains and the "lipid raft" concept. Curr. Med. Chem., 20, 4-21 (2013); Link here. This issue also contains several other reviews on lipids in membranes.

I always enjoy learning of the experiences of the pioneers of lipid science to understand how their research careers developed and why they went down specific paths. I have just been reading a fascinating autobiographical account of the career of Konrad Sandhoff, one of the pioneers in the study of the complex glycosphingolipids, such as gangliosides. He has been instrumental especially in revealing the roles of these lipids in lysosomal storage diseases as well as many other aspects of sphingolipid biochemistry. It is available in an open access journal (Sandhoff, K. My journey into the world of sphingolipids and sphingolipidoses. Proc. Japan Acad., B. Phys. Biol. Sci., 88, 554-582 (2012); DOI).

A correspondent has brought to my attention a paper describing a novel method for the preparative separation of trans- and cis-monoenoic fatty acids using membrane technology rather than chromatography methodology (Gupta, A. and Bowden, N.B. Separation of cis-fatty acids from saturated and trans-fatty acids by nanoporous polydicyclopentadiene membranes. ACS Appl. Mater. Interfaces, 5, 924–933 (2013); DOI). The width of the pores in the membrane are such that fatty acids with relatively linear chains can pass through, but the kinked cis-monoenes cannot.

Two weeks ago, I discussed a review paper that suggested that there were no definitive experiments to confirm the supposed benefits of dietary cis-monoenoic fatty acids. Now there is news of a major study (PREDIMED) with 7,500 subjects which finds that a Mediterranean diet supplemented with virgin olive oil and nuts (walnuts, almonds, hazelnuts) reduces the risk of suffering cardiovascular death, myocardial infarction or stroke by 30 percent. The diet has a relatively high fat content, but a significant difference from other studies may be that it does not use a refined oil and has other natural constituents. The report in the website Science Daily describes the results to non-nutritionists such as myself.

The current controversy about horse meat in the food chain is concerned more with fraud than with nutrition or safety issues. I cannot put my hands on a reference immediately, but I seem to recall that the triacylglycerols of horse fat contain much more linoleic and α-linolenic acids than beef. This is certainly the case in horse milk (Parodi, P.W. Positional distribution of fatty acids in triglycerides from milk of several species of mammals. Lipids, 17, 437-442 (1982); DOI).

© Bill Christie
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