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.

July 2nd, 2014

Lipid scientists tend to work within the bounds of one or other of the different kingdoms of life. If they are interested in animal lipids, they may not be aware of parallel work with plants or microorganisms, for example. I always enjoy reviews that try to bridge disciplines, and I have just come across one that does just that (Pohl, C.H. and Kock, J.L.F. Oxidized fatty acids as inter-kingdom signaling molecules. Molecules, 19, 1273-1285 (2014); DOI: 10.3390/molecules19011273). For example, the plant equivalents of isoprostanes, phytoprostanes, in pollen may be important factors in pollen allergy. Conversely, N-(17-Hydroxy)-linolenoyl-L-glutamine (volicitin) in oral secretions of insect larvae elicits a defense response in plants. There are many examples of signalling between fungi and animals, especially when the former take up arachidonic acid from the host and convert it to eicosanoids with innumerable biological activities. Similarly, there is inter-kingdom signalling between animals and bacteria, especially when eicosanoid metabolism is hijacked in the lungs, and between plants and fungi. I should mention that the review is open access.

Nature, Volume 510, Number 7503 has a number of review articles under the theme of 'Lipids in Health and Disease’, including an important article by C.N. Serhan on pro-resolving lipid mediators, which I found useful in updating the relevant webpage here.

June 25th, 2014

I have heard suggestions of various lipids being the most abundant on earth, including hopanoids and archaeal ethers because of their abundance in the microbial biome and their longevity in marine sediments over geological time. A prime candidate for the most abundant lipid on the surface of the earth is the plant waxes, because they cover every green leaf or blade of grass. They are also abundant in sediments, as I noticed that a study of isotope ratios in terrestrial plant waxes taken from marine sediment cores down to depths of 480 m, are being used to provide evidence of rainfall changes over a time-span of 24,000 years (www.sciencedaily.com).

I don’t recall having come across the term ‘self-lipid’ before, but it apparently means any lipid produced endogenously by an organism as opposed to one of foreign origin. A new study has found that novel self-lipids, methyl-lysophosphatidic acids, are anti-leukemia agents with considerable therapeutic potential (Lepore, M. et al. A novel self-lipid antigen targets human T cells against CDc leukemias. The Journal of Experimental Medicine, June 2014; DOI: 10.1084/jem.20140410). I don’t yet have access to the paper, but I presume that these are lysophosphatidic acids with a methyl group in position 2. I wonder if they are related metabolically to cyclic phosphatidic acid.

Biochemical and Biophysical Research Communications (Volume 446, issue 3) is devoted to the topic of ‘Oxysterols’ (edited by William Griffiths and Hans Jörnvall).

June 18th, 2014

For much of my research career, I have been reading of the supposed benefits of the ‘Eskimo’ diet on cardiovascular health, based upon a study published by two Danish investigators in the 1970s. The findings were promoted by the late Hugh Sinclair especially, who consumed large amounts of fish oil to test the theory on himself. A new article in press suggests that this theory has no scientific merit in that the authors of the original study did not in fact measure the actual prevalence of coronary artery disease but appear to have relied on hearsay. A new study in press demonstrates that Eskimo/Inuit populations have comparable mortality and morbidity due to CAD to their Caucasian counterparts (Fodor, G.J. et al. “Fishing” for the origins of the “Eskimos and heart disease” story. Facts or wishful thinking? A review. Can. J. Cardiol., in press http://www.onlinecjc.ca/article/S0828-282X(14)00237-2/abstract).

Biochimica Biophysica Acta - Biomembranes (Volume 1838, Part 6) is a special Issue devoted to the topic of “Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy” (edited by Pablo V. Escribá and Garth L. Nicolson). The focus is on the role of lipids in membranes, and the headline article by Professor Nicholson is open access (Nicolson, G.L. The Fluid-Mosaic Model of Membrane Structure: Still relevant to understanding the structure, function and dynamics of biological membranes after more than 40 years. Biochim. Biophys. Acta - Biomembranes, 1838, 1451-1466 (2014); DOI: 10.1016/j.bbamem.2013.10.019).

May 28th, 2014

What a difference a double bond can make! Prostaglandin PGE2 is notorious as one of the bad guys in terms of lipid function. It is a potent inflammatory agent and can have adverse effects on a host of human disease states, including cancer since it promotes survival of tumor cells by inhibiting apoptosis and inducing proliferation, and by increasing cell motility and migration (some of its beneficial effects are sometimes forgotten). PGE2 is of course derived from arachidonic acid (20:4(n-6)). In contrast, PGE3 is derived from eicosapentaenoic acid (20:5(n-3)) and so has an additional double bond in position 15. It has quite opposite effects to PGE2 and in fact has anti-proliferative activity in various cancers. A recent review discusses this (Yang, P. et al. Prostaglandin E3 metabolism and cancer. Cancer Letts, 348, 1-11 (2014); DOI: 10.1016/j.canlet.2014.03.010).

In recent weeks, I have highlighted review articles dealing with the role of prostaglandins, cholesterol and sterol oxides in Alzheimer’s disease in this blog. I have just got round to reading some of the articles in the special issue of Biochimica Biophysica Acta, dealing with sphingolipids, in which I found a review of the effects of ceramide on this disease (Yuyama, K. et al. Pathological roles of ceramide and its metabolites in metabolic syndrome and Alzheimer's disease. Biochim. Biophys. Acta, 1841, 793-798 (2014); DOI: 10.1016/j.bbalip.2013.08.002). I suspect that aberrant lipid metabolism may be a symptom rather than a cause, but there seems little doubt that the disease is multifactorial.

I am not sure what it says about me or my preoccupations, but one other article to catch my eye in this special issue deals with the effect of sphingolipids on longevity. Amongst a number of potential benefits to health, I should quote the following from the abstract – “perhaps the most interesting way to modulate sphingolipids and promote longevity is by lowering the activity of serine palmitoyltransferase, the first enzyme in the de novo sphingolipid biosynthesis pathway” (Huang, X. et al. Sphingolipids and lifespan regulation. Biochim. Biophys. Acta, 1841, 657-664 (2014); DOI: 10.1016/j.bbalip.2013.08.006). I need a holiday.

May 21st, 2014

In my blog last month, I drew attention to a paper pointing out errors in the literature because of the incorrect identification of an isomer generated from DHA by the action of plant 15-lipoxygenase as protectin D1, but now better designated 'protectin DX'. The latter is manufactured with relative ease and is the only isomer available commercially. Now, it is reported that this isomer has important biological properties in its own right, distinct from those of the natural isomers. It appears to have the potential to treat insulin resistance and type 2 diabetes (White, P.J. et al. Protectin DX alleviates insulin resistance by activating a myokine-liver glucoregulatory axis. Nature Medicine, 2014; DOI: 10.1038/nm.3549).

The word ‘lipidomics’ has given respectability to lipid analytical studies, many of which in recent years have demonstrated key aspects of lipid metabolism. In my research career, I was often told that such work was "merely analytical". If you need a demonstration of the importance of the modern approach you only need to read the abstract (though I recommend more) of a review of the subject in relation to platelets (O'Donnell, V.B. et al. Platelet lipidomics modern day perspective on lipid discovery and characterization in platelets. Circ. Res., 114, 1185-1203 (2014); DOI: 10.1161/CIRCRESAHA.114.301597).

Two weeks ago, I drew attention to two review articles dealing with the potential effects of sterols on Alzheimer's disease. A new publication deals with the effects of prostaglandins (Cudaback, E. et al. Therapeutic implications of the prostaglandin pathway in Alzheimer's disease. Biochem. Pharm., 88, 565-572 (2014); DOI: 10.1016/j.bcp.2013.12.014).

May 14th, 2014

The editors of the Journal of Biological Chemistry have selected as their paper of the week one dealing with the effects of lipids on cognitive function. The process is complex, but it seems that Fatty Acid-binding Protein 5 both promotes the hydrolysis of anandamide into arachidonic acid and thus reduces brain endocannabinoid levels; the resulting arachidonic acid is transferred directly to the nucleus where it delivers it to PPARβ/δ, enabling its activation and regulation of hippocampal cognitive function. (Yu, S. et al. Fatty acid-binding protein 5 (FABP5) regulates cognitive function both by decreasing anandamide levels and by activating the nuclear receptor peroxisome proliferator-activated receptor β/δ (PPARβ/δ) in the brain. J. Biol. Chem., 289, 12748-12758 (2014); DOI: 10.1074/jbc.M114.559062).

Fatty acids are found in nature with every conceivable substituent group, but those with an amine substituent are perhaps surprisingly rare. Before today, the only ones I knew of were C14 to C17 fatty acids with an amine group in position 3 in a lipopeptide from Bacillus subtilis. Now, 3-amino-9-methyldecanoic acid has been found as a constituent of glycosylated lipopeptides from myxobacteria (Etzbach, L. et al. Cystomanamides: structure and biosynthetic pathway of a family of glycosylated lipopeptides from myxobacteria. Org. Letts, 16, 2414-2417 (2014); DOI: 10.1021/ol500779s). The amine group can be N-glycosylated in some of the lipopeptides.

The March issue of Current Opinion In Clinical Nutrition And Metabolic Care is devoted to the topic of “Lipid Metabolism And Therapy” (edited by Philip C. Calder and Richard J. Deckelbaum). I don’t have access to the journal but the eight review articles look interesting.

May 7th, 2014

Scottish thistleTwo recent reviews discuss the role of cholesterol in Alzheimer’s disease. The first points out that high blood cholesterol levels have been suggested to be a risk factor for the disease, and this has been supported by some retrospective epidemiological studies. However, prospective studies with statins have failed to show beneficial effects, and possible reasons for this are discussed (Wood, W.G. et al. Cholesterol as a causative factor in Alzheimer's disease: a debatable hypothesis. J. Neurochem., 129, 559-572 (2014); DOI: 10.1111/jnc.12637). The second review suggests that oxysterols, rather than cholesterol per se, may be more important players, since these can cross the blood brain barrier with relative ease and then modulate the expression of enzymes, receptors and transporters involved in brain functions (Gosselet, F. et al. Effects of oxysterols on the blood-brain barrier: Implications for Alzheimer's disease. Biochem. Biophys. Res. Commun., 446, 687-691 (2014); DOI: 10.1016/j.bbrc.2013.11.059). The same issue of the latter journal is devoted to the topic of "oxysterols", so there are many more papers that will be of interest to specialists in this field, including several on analytical methodology.

A less serious health problem is baldness in men, though no doubt it causes much anguish to sufferers. A new paper suggests that a lipid may be involved – prostaglandin D2. Interference with its metabolism has the potential to lead to new therapies (Nieves, A. and Garza, L.A. Does prostaglandin D2 hold the cure to male pattern baldness? Exp. Dermatol., 23, 224-227 (2014); DOI: 10.1111/exd.12348).

The oddest lipid story of the week is a report that acetylated triacylglycerols accumulate in the pupae of a type of insect. This remains liquid during winter when the insect is frozen so can serve as a source of energy to maintain life (Marshall, K.E. et al. Seasonal accumulation of acetylated triacylglycerols by a freeze-tolerant insect. J. Exp. Biol., 217, 1580-1587 (2014); DOI: 10.1242/jeb.099838).

April 30th, 2014

I have more news on lipids that are beneficial to health this week. The journal Anti-Cancer Agents in Medicinal Chemistry, Volume 14 - Number 4 is a special issue devoted to the theme of “Antitumor alkylphospholipid analogs: a promising and growing family of synthetic cell membrane-targeting molecules for cancer treatment” (edited by Faustino Mollinedo). All the articles are open access (DOI: 10.2174/1871520614999140313160011). Such synthetic alkylphospholipids are similar in structure to platelet-activating factor, and they are of great interest to pharmaceutical companies as they have antiproliferative effects on tumours. They differ from existing anti-cancer agents in that they do not interfere with the DNA, but rather influence lipid metabolism and signalling pathways in membranes where they tend to accumulate. They appear to have no effect on normal cells.

A further publication with promising news on the health front in relation to lipids to have received some publicity in the scientific press is a demonstration that inhibition of glucosyl- and lactosylceramide synthase activity can be beneficial towards atherosclerosis in laboratory animals fed a high-fat, cholesterol-laden diet – See Science Daily News.

The mechanism for the biosynthesis of the vitally important lipid phosphatidylinositol in Eukaryotes from CDP-diacylglycerol and inositol has been studied intensively for some years, and it was something of a surprise to find that a quite different mechanism operated in Archaea with inositol-1-phosphate as a key precursor. A new study suggests that this second pathway is universal in Archaea and those Bacteria that contain inositol phospholipids (Morii, H. et al. Ubiquitous distribution of phosphatidylinositol phosphate synthase and archaetidylinositol phosphate synthase in Bacteria and Archaea, which contain inositol phospholipid. Biochem. Biophys. Res. Commun., 443, 86-90 (2014); DOI: 10.1016/j.bbrc.2013.11.054).

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..

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: July 2nd, 2014 Credits/disclaimer © AOCS