An occasional series of notes on publications or other items dealing with lipid science that seem to be of particular interest to the author Bill Christie. Inevitably, the selection is highly personal and subjective.

April 23rd, 2014

Two papers dealing with errors in scientific publications caught my eye this week. The first points out that such fatty acids as docosahexaenoic (22:6(n-3)) and eicosapentaenoic(20:5(n-3)) acids simply do not occur in higher plants, although their presence is frequently reported from gas chromatographic analysis. I have often made the point myself that a peak on a GC chart is simply ink on paper and has no further meaning unless backed up by spectroscopic or other chromatographic data. Familiar samples may not need such confirmation but novel samples certainly do (Guil-Guerrero, J.L. Common mistakes about fatty acids identification by gas-liquid chromatography. J. Food Comp. Anal., 33, 153-154 (2014); DOI: 10.1016/j.jfca.2013.12.006). Forgive me for blowing my own trumpet for a moment, but there is one and I believe only one definitive identification of arachidonic and eicosapentaenoic acids in a higher plant, but in a relatively primitive Gymnosperm (DOI: 10.1007/s11745-999-0460-y).

The second paper points out that an isomer generated from DHA by the action of plant 15-lipoxygenase was misidentified as the dihydroxylated and non-cyclic docosatriene protectin D1. This incorrectly labelled compound was made available commercially and has been used in a number of published studies. In fact, this isomer (now designated ‘PDX’) has different biological properties from authentic PD1, so there are several erroneous reports in the literature (Balas, L. et al. Confusion between protectin D1 (PD1) and its isomer protectin DX (PDX). An overview on the dihydroxy-docosatrienes described to date. Biochimie, 99, 1-7 (2014); DOI: 10.1016/j.biochi.2013.11.006).

Although the methodology is out of the mainstream of lipid research, there is an interesting report in the popular scientific press that it is now possible to identify brown fat in humans by means of an MRI scan. This tissue has become a target for therapies that might enable the more efficient burning of excess fat to help patients with obesity problems or diabetes, so the new technique should be a helpful step forward (see Science Daily News)

April 16th, 2014

The current issue of Advances in Biological Regulation contains a number of interesting review articles on the biochemistry and analysis of lipids, including two that deal with how lipidomic studies are leading to new advances in the biochemistry of lipids in specific tissues. However, the one that really caught my eye is by Philip W. Majerus and recounts the discovery of how aspirin is involved in prostaglandin biosynthesis, before continuing with a discussion of how aspirin may be beneficial in many different clinical situations (Majerus, P.W. An aspirin a day. Adv. Biol. Reg., 54, 231-241 (2014); DOI: 10.1016/j.jbior.2013.09.011).

The N-acylethanolamides are a fascinating class of lipids, which clearly demonstrate that the fatty acid component is not simply a hydrophobic appendage but is vital to the activity. The palmitoyl, arachidonoyl and oleoyl derivatives all have different and quite distinctive biological properties and functions. I was reminded of this by a new review article on N-palmitoylethanolamide, which is now undergoing clinical trials for the relief of chronic pain (Skaper, S.D. et al. Palmitoylethanolamide, a naturally occurring disease-modifying agent in neuropathic pain. Inflammopharmacology, 22, 79-94 (2014); DOI: 10.1007/s10787-013-0191-7).

A new review article (open access) explores the relationship between sphingolipids and prostaglandin formation. In particular, a number of different sphingolipids are involved in the regulation of phospholipase A2 activity, the rate-limiting enzyme, and also of cyclo-oxygenase-2 (Nakamura, H. and Murayama, T. The role of sphingolipids in arachidonic acid metabolism. J. Pharm. Sci., 124, 307-312 (2014); DOI: 10.1254/jphs.13R18CP).

Gary List and Douglas Bibus have published a memoir of Ralph T. Holman (Biographical Memoirs of the National Academy of Sciences (2014)). It complements that published here..

April 9th, 2014

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

The most unusual lipid paper to cross my path this week is - Khrameeva, E.E. et al. Neanderthal ancestry drives evolution of lipid catabolism in contemporary Europeans. Nature Commun., 2014; 5, 3584; DOI: 10.1038/ncomms4584). It appears that contemporary humans of European descent have a greater than threefold excess of Neanderthal-like sites in those genes involved in lipid catabolism, in comparison to Asian or African populations. If you are interested, the paper is open access.

The glycosylglycerolipids such as mono- and digalactosyldiacylglycerols are vital molecules and one of the keys to life in that they are essential to the membranes involved in photosynthesis from cyanobacteria to chloroplasts of eukaryotic cells. Two new review articles (sharing key authors) discuss this from a similar perspective (Boudiere, L. et al. Glycerolipids in photosynthesis: Composition, synthesis and trafficking. Biochim. Biophys. Acta Bioenergetics, 1837, 470-480 (2014); DOI: 10.1016/j.bbabio.2013.09.007; Petroutsos, D. et al. Evolution of galactoglycerolipid biosynthetic pathways – From cyanobacteria to primary plastids and from primary to secondary plastids. Prog. Lipid Res., 54, 68-85 (2014); DOI: 10.1016/j.plipres.2014.02.001). During phosphate deprivation, these lipids seem to be able to replace phospholipids in other plant membranes. For such reasons, I have argued that the Lipid Maps consortium should recognise glycosylglycerolipids in a similar hierarchy to phospholipids in their classification scheme, but so far to no avail.

April 2nd, 2014

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

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

March 26th, 2014

We hear so much bad news about lipids or ‘fat’, that I am always intrigued by news of beneficial lipids and especially of applications as pharmaceuticals to fight disease. I was therefore intrigued by a new review on bacterial lipopeptides (Schneider, T. et al. Cyclic lipopeptides as antibacterial agents - potent antibiotic activity mediated by intriguing mode of actions. Int. J. Med. Microbiol., 304, 37-43 (2014); DOI: 10.1016/j.ijmm.2013.08.009). They can consist of short linear chains or cyclic structures of amino acids, linked to a fatty acid via ester or amide bonds or both. Often the amino acids are of the D- rather than the usual L configuration, presumably to resist the action of proteases. The fatty acid constituents add to the variability, for example in chain-length (C6-C18) and often the presence of hydroxyl groups and/or iso- or anteiso-methyl branches. Many have surfactant, antibacterial or antifungal properties and have attracted interest from industry. For example, polymixins act by binding to the lipid A moiety of lipopolysaccharides, and they are used to treat a variety of infections caused by Gram-negative bacteria, especially in topical applications, such as wound creams and eye or ear drops. While they have been considered to be too toxic to be used as systemic antibiotics, they are now finding application against multi-drug-resistant Gram-negative bacilli. Synthetic variants of polymixins and other lipopeptides are now being developed with reduced toxicity and improved antibacterial properties.

March 19th, 2014

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

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

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

March 12th, 2014

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

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

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

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

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

March 5th, 2014

Scottish thistleThe stratum corneum layer is unique in that it contains relatively high levels of ceramides (as much as 50% of the total lipids), including distinctive O-acylceramides found nowhere else. There is a special issue of Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids (Vol. 1841, Issue 3 pp. 279-474 (March 2014) dealing with “The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier” (edited by K.R. Feingold and P.M. Elias). There are more than 20 articles, a number of which are concerned with the biochemistry and function of these unique ceramides. By coincidence, there is a fascinating review on ceramides in Progress in Lipid Research (online only at the moment) (Castro, B.M. et al. Ceramide: A simple sphingolipid with unique biophysical properties. Prog. Lipid Res., 54, 53-67 (2014); DOI: 10.1016/j.plipres.2014.01.004).

A new review poses an interesting question (Wang, H. and Eckel, R.H. What are lipoproteins doing in the brain? Trends Endocrinol. Metab., 25, 8-14 (2014); DOI: 10.1016/j.tem.2013.10.003). It appears that they are doing quite a lot. For example, I was unaware that HDL can cross the blood-brain barrier, though most are synthesised within the central nervous system including the most abundant apolipoproteins (Apo E and Apo J). Lipoproteins regulate neurological behaviour via specific receptors, and they take part in the regulation of body weight and energy balance.

February 26th, 2014

I have never liked the term ‘endocannabinoids’, which I presume means ‘cannabinoids within the body’. As a new review of the topic, which happily is open access, points out, it is the exogenous cannabinoids that have hijacked the brain’s neurotransmitter system involving anandamide and 2-arachidonoylglycerol - not the reverse (Piomelli, D. More surprises lying ahead. The endocannabinoids keep us guessing. Neuropharmacology, 76, 228-234 (2014); DOI: 10.1016/j.neuropharm.2013.07.026). Perhaps we should rename ‘cannabinoids’ as ‘exoanandamides’. Joking aside, an interesting feature of the review is that it discusses what we don’t know about the subject as well as the latest findings. By coincidence I came across a quotation by Niels Bohr this week – “If you aren’t confused by quantum physics, then you haven’t really understood it”. Substitute ‘lipid signalling’ for ‘quantum mechanics’ and you have my feelings on the subject.

We are used to hearing bad news about lipids in relation to disease, so I was pleased to read of some fascinating new developments in relation to resolvins and protectins, anti-inflammatory lipids derived from long-chain omega-3 fatty acids. It appears that there are a number of animal experiments to indicate that these lipids can ameliorate the effects of many bacterial and viral diseases. The final line of the abstract is “If the effects of these mediators translate from pre-clinical studies into successful clinical trials, they represent promising new strategies in managing infectious disease” (Russell, C.D. and Schwarze, J. The role of pro-resolution lipid mediators in infectious disease. Immunology, 141, 166-173 (2014); DOI: 10.1111/imm.12206). A more general review of the biochemistry of these lipids was published at the end of last year (Serhan, C.N. and Chiang, N. Resolution phase lipid mediators of inflammation: agonists of resolution. Curr. Opinion Pharmacol., 13, 632–640 (2013); DOI: 10.1016/j.coph.2013.05.012).

February 19th, 2014

In the last years or so a number of papers have appeared that deal with arsenolipids in fish oils. These may consist of long-chain hydrocarbons with a terminal dimethylarsinoyl moiety, first described as recently as 2008, or fatty acids resembling those found conventionally but with a dimethylarsinoyl moiety replacing the terminal methyl group. I have lost count of how many of the latter have been reported to date but it must be more than twenty. One further type of arsenolipid with a long alkyl chain has now been reported that consists of cationic trimethylarsenio fatty alcohols of which two molecular species have so far been detected in fish oils (Amayo, K.O. et al. Novel identification of arsenolipids using chemical derivatizations in conjunction with RP-HPLC-ICPMS/ESMS. Anal. Chem., 85, 9321-9327 (2013); DOI: 10.1021/ac4020935).

a cationic trimethylarsenio fatty alcohol

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

Also open access, in line with ACS policy as it is in the first issue of the journal for the year, is a review on the methodology of lipidomics (Li, M. et al. Analytical methods in lipidomics and their applications. Anal. Chem., 86, 161-175 (2014); DOI: 10.1021/ac403554h).

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

February 12th, 2014

Trust a Scotsman to find a bargain. In recent years, it has become dogma in nutritional circles that dietary trans-fatty acids are detrimental to health. There are innumerable publications in the biological literature to document this, but it can be harder to find information on chemical properties. A new and substantial review in the ACS journal Chemical Reviews remedies this, and fortuitously, as it is in the first issue of the year, it is open access (Chatgilialoglu, C. et al. Lipid geometrical isomerism: from chemistry to biology and diagnostics. Chem. Rev., 114, 255-284 (2014); DOI: 10.1021/cr4002287). Amongst many topics, the review covers the analysis and characterization of trans fatty acids, natural sources and chemical reactivity. The same issue of the journal also contains two articles on the chemistry and biochemistry of carotenoids and retinoids, which should be of interest to biochemists (and also open access).

Another group of important biologically active fatty acids, which are currently attracting great interest, are the nitro-conjugated linoleic acids. A new paper in the ACS Journal of Organic Chemistry discusses the chemical synthesis and characterization of these fatty acids (Woodcock, S.R. et al. Biomimetic nitration of conjugated linoleic acid: formation and characterization of naturally occurring conjugated nitrodienes. J. Org. Chem., 79, 25-33 (2014); DOI: 10.1021/jo4021562). Studies of the biological properties should be facilitated by readier access to model compounds. Again as it is in the first issue of the year, this paper is open access.

Past items are archived for about a year here..

W. Christie

James Hutton Institute (and Mylnefield Lipid Analysis), Invergowrie, Dundee (DD2 5DA), Scotland.

Author Updated: April 23rd, 2014 Credits/disclaimer AOCS