Lipid Matters - A Personal Blog

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

March 14th, 2018

Scottish thistle Following on from my discussion of 16:1 isomers in my last blog, a new review of the biological effects of palmitoleic acid (9-16:1), sometimes termed a lipokine, has been published (de Souza, C.O. et al.) Is palmitoleic acid a plausible nonpharmacological strategy to prevent or control chronic metabolic and inflammatory disorders? Mol. Nutr. Food Res., 62, 1700504 (2018);  DOI). After a thorough review of the evidence, the answer to the question posed in the title seems to be that we do not yet know, although the results with animal studies are promising, and that further human-based research is required. This publication and those for the next two topics are open access.

I also mentioned the essential fatty acids last week, and a new review discusses the evolutionary significance of the biosynthesis of linoleate in primitive invertebrates, including some species of insects, nematodes and pulmonates (air-breathing slugs and snails) (Malcicka, M. et al. An evolutionary perspective on linoleic acid synthesis in animals. Evol. Biol., 45, 15-26 (2018);  DOI). It appears that there is no consistent lineage in the occurrence of the ability to produce linoleate, not even within any given family, and that this ability was lost and repeatedly gained during the evolution of distinct invertebrate groups. One key factor may have been the development of bifunctionality in desaturase enzymes (Δ12/Δ15). Much of the information was new to me, and my first thought was for endosymbiont-mediated linoleate synthesis, but it seems that no examples of this have yet been discovered. Of course, much of the discussion is of necessity speculative, but the paper is certainly thought-provoking.

I suppose that few of us have given much thought to the function of butyric acid in animal metabolism. From my years in an animal research institute, I was well aware of its importance in the metabolism of ruminant animals, and of course it is an important component of the triacylglycerols of cow's milk, where it is located specifically in position sn-3. However, it is also produced in significant amounts by microbial fermentation of dietary fibers in the lower intestinal tract of all animals, and a new review describes its many functions within the tissues of the host animal (Liu, H. et al. Butyrate: a double-edged sword for health? Adv. Nutr., 9, 21-29 (2018);  DOI).

While I am on the subject of bioactive fatty acids, the first report of the occurrence of resolvins in a non-mammalian tissue (marine diatoms) has just appeared (Rettner, J. et al. Survey of the C20 and C22 oxylipin family in marine diatoms. Tetrahedron Letts., 59, 828-831 (2018);  DOI).

March 7th, 2018

The essential nature of linoleic acid in the diet was first reported in 1929 by George and Mildred Burr, although it was many years before this was recognized by the scientific community at large. It was much later in the last century before many other vital functions of specific fatty acids were recognized, for example palmitic and myristic acids as covalent conjugates with proteins to target them to membranes or octanoic acid that is required for grehlin activation. Three 16:1 isomers are known in human tissues with double bonds in the 6, 7 and 9 positions. Of these, 9-16:1 or palmitoleate is best known and has been termed a 'lipokine', i.e. it is an adipose tissue-derived hormone, which amongst other effects stimulates the action of insulin in muscle; it is linked very specifically to a conserved serine residue in the Wtn family of proteins (O-acylated proteolipids) involved in adipose tissue development, and it is essential for their function. 7-16:1 has some biological functions in common with 9-16:1, and it is regarded as an anti-inflammatory molecule, while 6-16:1 or sapienic acid is found mainly in human skin and has biocidal properties. Now all three isomers have been detected in macrophages both from mice and humans (Astudillo, A.M. et al. Occurrence and biological activity of palmitoleic acid isomers in phagocytic cells. J. Lipid Res., 59, 237-249 (2018);  DOI)). However, in contrast to the other two isomers, the levels of 6-16:1 were not regulated by the activation state of the cell, and it appears that we do not yet know its function in these cells. Incidentally, it seems that the trivial name 'sapienic' from Homo sapiens is now a misnomer as it is now shown to be present in mice - brings to mind the John Steinbeck novel - "Of Mice and Men" (I may be showing my age again).

I can recommend an authoritative review of sphingolipid biosynthesis and function that has just been published (Hannun, Y.A. and Obeid, L.M. Sphingolipids and their metabolism in physiology and disease. Nature Rev. Mol. Cell Biol., 19, 175-191 (2018);  DOI).

February 28th, 2018

Scottish thistle When I do my weekly literature search, I have to scan lists of around 400 references to select those that are useful to me or should appear in my literature survey section, and then transfer them to my data base in an appropriate format. I can only spare about 20 minutes for the selection phase and I have to rely on the clarity of the titles, so inevitably I miss some important papers; also, the search algorithm I use is less than perfect. I am therefore grateful when correspondents point out items that I have missed. For example, two publications from 2016 dealing with novel methodology for the determination of trans fatty acids involving gas chromatography-vacuum ultraviolet spectroscopy have just been drawn to my attention, and they are listed in my current monthly analysis list (and will appear subsequently in that for 2016).

The Lipid Maps "Lipid Of the month" for February (see their home page) was another novelty for me, i.e. the elovanoids - C32 and C34 analogues of the protectins, which have been found in retinal cells. I presumably missed these because my weekly search did not contain suitable key words. Again, I have gone back to the Web of Science, to recover the relevant references which are now in my new monthly list for "Lipid essentials". What intrigued me especially, when I read the original papers was the fact that the protectins per se are derived from DHA in position sn-2 of phospholipids, while the precursors of the elovanoids are in position sn-1. This implies that the enzymes involved in the release of the two classes of fatty acid substrates are very different and so must be the stimulatory and regulatory mechanisms. There is a comparable difference for eicosanoid and anandamide biosynthesis; the arachidonic acid for the former comes from position sn-2 of phospholipids, while that for the latter comes from position sn-1.

This brings me back to an old theme of mine that in the world of lipidomics positional distributions are not given sufficient weight in comparison to molecular species analyses. I am sure that positional distributions obtained by mass spectrometry offer nothing near the precision of the older methods using selective lipases, but I would like to see an experimental comparison.

February 21st, 2018

As I have mentioned from time to time in this blog, I am an armchair analyst these days so I am reluctant to endorse what seems novel methodology. I do read and I can comment, however, and others can correct me if they wish. For example, a major problem with HPLC of all polar lipids has always been adsorption on columns. It is usually necessary to add ionic species to the mobile phase to get sharp peaks, and these can cause detection problems or degrade stationary phases. I never attempted to analyse CoA esters in my research days, but I am aware of some of the technical difficulties and I found a new publication had some interesting ideas to eliminate adsorption effects (Abranko et al. Comprehensive quantitative analysis of fatty-acyl-Coenzyme A species in biological samples by ultra-high performance liquid chromatography-tandem mass spectrometry harmonizing hydrophilic interaction and reversed phase chromatography. J. Chromatogr. A, 1534, 111-122 (2018);   DOI); the paper is open access. The authors tested various ammonium salts in the mobile phase and found that ammonium bicarbonate (10 mM adjusted to pH 8.5) was much the best over the whole range of chain-lengths, aided appreciably by the incorporation of a 0.1% phosphoric acid wash step between injections. Of course, the nature of the stationary phase is also important, and I have complained in the blog from time to time of the use of the term 'HILIC chromatography', which tells us nothing about the mode of interaction with analytes, adsorption, ion-exchange, etc. In this work, a Waters BEH HILIC column was used in part; it took me an age to find what 'BEH' implied, although I am little further forward in my understanding.

An interesting article by a young scientist was published in the Guardian newspaper last week complaining about the inappropriate use of metrics to evaluate scientific research. During much of my career, the pressures were different and I did not have to pay too much attention to this aspect of publication; my usual philosophy in selecting a particular journal for a new publication was whether it would reach the intended audience. The important objective was to see that any new information I had uncovered was disseminated - not how. It is a different world now and I recognize that young scientists starting on their careers face real difficulties. Many of the best papers I read have multiple authors (often into double figures) because multiple technologies and expertise may be required to provide answers. At the start of their careers, scientists working on their own can only hope to make incremental progress in their chosen fields, and I would hope that this would be recognized by scientific administrators. In my later years of research, my pet hate was projected 'milestones' - if I knew where the results were going to lead 2-3 years ahead, the work was not worth doing.

What really worries me now having just reviewed the above comments, is that I am beginning to sound like my father (no disrespect intended) in his later years - "when I was a boy, etc., etc.!" It is bad enough that I now look like he did. I will have to try to resurrect the youthful inner me.

February 14th, 2018

In plants, glycerolipid biosynthesis in chloroplasts has long been termed the "prokaryotic pathway", and it produces galactosyldiacylglycerols and phosphatidylglycerol with C18 acids in position sn-1 and C16 acids in position sn-2. This pattern is seen in cyanobacteria and it has been assumed that the similarity was a consequence of endosymbiosis during evolution. A new study demonstrates that this is not true (Sato, N. and Awai, K. "Prokaryotic Pathway" is not prokaryotic: noncyanobacterial origin of the chloroplast lipid biosynthetic pathway revealed by comprehensive phylogenomic analysis. Genome Biol. Evolution, 9, 3162-3178 (2017);  DOI); the paper is open access. It is now evident that the two steps of acylation in cyanobacteria and chloroplasts utilize enzymes that have no phylogenetic relationship. The structural differences in the diacylglycerol moieties of galactolipids from various species of algae and higher plants originate in fact in compartmentalization of the biosynthetic pathways or precursors in cells, especially between the chloroplasts and endoplasmic reticulum, each compartment having its own distinctive enzymes with characteristic specificities (see my web page on galactosyldiacylglycerols for further discussion).

My prize for the most unusual new lipid that I have encountered this year so far goes to a novel arsenolipid. The unicellular marine alga Dunaliella tertiolecta contains phytyl 5‑dimethylarsinoyl-2-O-methyl-ribofuranoside as 35 to 65% of the total arsenolipids. Apart from its arsenic content, this lipid is unique in containing both an ether-linked phytyl group and a 2‑O‑methylriboside of a type normally found only in RNA. (Glabonjat, R.A. et al. A 2-O-methylriboside unknown outside the RNA world contains arsenic. Angew. Chem.-Int. Ed., 56, 11963–11965 (2017);  DOI.

Formula of phytyl 5-dimethylarsinoyl-2-O-methyl-ribofuranoside

There is an interesting article in Nature on the importance of scientific blogs. Regretfully, they missed this one!

February 7th, 2018

In my blog of two weeks ago, I discussed the therapeutic potential of nitro fatty acids and in particular how subcutaneous injection of nitro-oleic acid suppressed allergic contact dermatitis in mice. Alas, a new publication from the same research group reports that topical applications have the opposite effect (Mathers, A.R. et al. Topical electrophilic nitro-fatty acids potentiate cutaneous inflammation. Free Rad. Biol. Med., 115, 31-42 (2018);  DOI). The problem appears to lie in the finding that nitro-conjugated linoleate is formed naturally "in the skin microenvironment as products of cutaneous inflammatory responses and, in high local concentrations, may exacerbate inflammatory skin diseases".

I couldn't have put better the philosophy implied in the title to an editorial contribution to a Nature journal (Marx, V. Fats add structure, they signal, they interact. In the lab, lipids are tough to work with but worth the challenge. Nature Methods, 15, 35-38 (2018);  DOI).

I always enjoy reading the personal reminiscences of lipid scientists and that by Dennis E. Vance was no exception, and it has a title that recalls my previous paragraph (From masochistic enzymology to mechanistic physiology and disease. J. Biol. Chem., 292, 17169-17177 (2017);  DOI). However, it also served to remind me that a new edition of one of the most valued books in my personal library was now available, but with new editors (Ridgway, N.D. and McLeod, R.S. Biochemistry of Lipids, Lipoproteins and Membranes, 6th Edition. (Elsevier, Amsterdam) (2016) - see Science Direct) - and prompted recourse to Amazon. It covers much the same range of topics as in previous editions, but often with replacement authors, and I expect to make good use of it. As expected with modern textbooks it is very well produced from a technical standpoint. Comparison with the book by Gurr et al. (Lipids: Biochemistry, Biotechnology and Health, 6th Edition), which I reviewed some months ago is probably unfair, as they probably aim at different audiences. My superficial first impression is that the new book goes into the subjects in greater depth but the coverage is not so exhaustive. For example, it was of great help to me in updating my web page on proteolipids, but there is no mention of "endocannabinoids" or "lipid sulfates" in the index.

January 31st, 2018

Scottish thistle It has been a puzzle to me how the endocannabinoids, anandamide and 2-arachidonoylglycerol, can have so many different functions in a given tissue while operating through a single G protein receptor. A new review illustrates how this happens using brain as the model (Busquets-Garcia, A. et al. CB1 receptor signaling in the brain: extracting specificity from ubiquity. Neuropsychopharmacology, 43, 4-20 (2018);  DOI). It seems that endocannabinoid receptors exert their wide variety of different cellular effects by specific interactions with many other G proteins and that this is dependent on such factors as cell type, subcellular location and cellular functional state. Within a given tissue, expression of a receptor can vary between different locations. For example, in brain some types of neuron contain very high levels of CB1 receptor protein, whereas others have much lower levels; there are even lower levels in some regions of the hypothalamus and astroglial cells. In turn, variation in the location of CB1-interacting proteins may have a role in the cell-specific modulation of endocannabinoid signalling. This paper is part of a special issues on "Cannabinoids and endocannabinoids" and the only one to be open access. However, most of the other contributions appear to be more suitable for specialists.

The number of different molecular species of lipids in a given cell is astonishing (at least 1,000). Yet it is surprising how often only a single molecular species of a given lipid is required for optimum activity in a specific function. Cardiolipin in heart muscle is a prime example. If it had say 10 different fatty acid components, as is usual in most glycerolipids, together with the four different positions for acylation, there could in theory be 104 different molecular species. Instead, as is well known, linoleic acid is by far the most abundant fatty acid (as much as 80%) and the tetralinoleoyl species amounts to at least half the total. Many have speculated as to why this should be so, but a new publication demonstrates that if linoleate is displaced by docosahexaenoate in mitochondrial cardiolipin in the rat then the enzyme activities of the respiratory complexes are greatly reduced, apparently by preventing the formation of phospholipid domains that regulate enzyme activity (Sullivan, E.M. et al. Docosahexaenoic acid lowers cardiac mitochondrial enzyme activity by replacing linoleic acid in the phospholipidome. J. Biol. Chem., 293, 466-483 (2013);  DOI). I wonder what would be the result if they tried to displace linoleate with palmitate as this is the most abundant fatty acid in testis cardiolipin and has a much less mobile conformation than DHA.

January 24th, 2018

Nitro fatty acids are fascinating 21st Century molecules with important anti-inflammatory properties (they were first recognized as natural lipid components in 1999). In tissues, they occur in the free form, bound reversibly to thiol-containing proteins and glutathione, and as esters in triacylglycerols and phospholipids. In human serum in addition to non-covalent binding with albumin, nitro-conjugated linoleic acid has been shown to form covalent adducts at Cys-34 (Michael reaction), suggesting that this may be a means of systemic distribution. The effective concentrations of nitro fatty acids in tissues are reduced by this means, but a mechanism for the reversal of the reaction has been revealed under conditions of oxidative stress in vitro in plants at least. Reactive oxygen and nitrogen species, as represented by hydrogen peroxide and peroxynitrite, respectively, have the ability to oxidize cysteine-adducted nitro fatty acids with the release of free nitroalkenes, which can presumably then exert their anti-inflammatory effects (Padilla, M.N. et al. In vitro nitro-fatty acid release from Cys-NO2-fatty acid adducts under nitro-oxidative conditions. Nitric Oxide, Biol. Chem., 68, 14-22 (2017); DOI). Incidentally, nitro fatty acids are present in olives and virgin olive oil at concentrations that may be significant biologically, and it has been argued that they could be one reason for the beneficial effects of the Mediterranean diet. Their clinical potential is under active investigation, for example to inhibit cutaneous inflammation (Mathers, A.R. et al. Electrophilic nitro-fatty acids suppress allergic contact dermatitis in mice. Allergy, 72, 656-664 (2017); DOI).

The concept of lipid rafts in membranes, i.e. laterally segregated domains usually enriched in sphingolipids and cholesterol that provide platforms for signalling proteins, is now well established in the scientific literature. The terms termed 'membrane rafts', 'nanodomains' and 'microdomains' tend to be used interchangeably, but a new review suggests that in plants at least, different types of domain exist with differing compositions and functions so more precise definitions are required (Ott, T. Membrane nanodomains and microdomains in plant-microbe interactions. Curr. Opinion Plant. Biol., 40, 82-88 (2017); DOI).

Two substantial review articles deal with the methodology of lipidomics (Rustam, Y.H. and Reid, G.E. Analytical challenges and recent advances in mass spectrometry based lipidomics. Anal. Chem., 90, 374-397 (2018); DOI. And - Hu, T. and Zhang, J.L. Mass-spectrometry-based lipidomics. J. Sep. Sci., 41, 351-372 (2018); DOI). The second of these is open access.

January 17th, 2018

In recent years, I have written to several journals, most recently two months ago, to point out major errors in the interpretation of mass spectra in published papers. On most occasions, the journal has replied promptly and has promised to publish a correction - I still have to see one. Usually, the problem lies in computerized identification of methyl esters of fatty acids, as computers don't recognize that they cannot distinguish between positional and geometrical isomers of monoenoic or dienoic fatty acids, but often the authors (and reviewers) have simply not done their homework. One example, was a report of iso-methyl branched fatty acids in higher plants on the basis of a large ion equivalent to m/z = M-43; it has been known since the 1950s that this is common to mass spectra of all straight-chain fatty acids as a result of a complex rearrangement involving expulsion of carbons 2 to 4.

Problems also arise with interpretation of mass spectra of dimethyloxazoline derivatives of fatty acids. The first authors described a simple rule for how to locate double bonds. However, lacking appropriate standards, they were not aware that the rule did not apply when the double bonds were close to either end of the molecule. In addition, 3-isomers isomerize to 2-isomers on derivatization. The answer is to compare with authentic spectra, such as those on this website. Unfortunately, in spite of my best efforts, there are many flawed publications out there.

The ISI Web of Science seems to be just catching up after the holiday, and my weekly literature seach has given me three special review volumes to digest. I will list selected individual papers in my next literature update, but many of you will wish to consult the original journals for the full list. The December issue of Current Opinion in Plant Biology (Volume 40, Pages 1-168 (2017)) is devoted to the topic of "Cell biology: Membrane dynamics - being at the right place at the right time" (edited by Eugenia Russinova and Karin Schumacher) and includes a number of reviews of interest to plant lipid biochemists. The open access journal Antioxidants (Volume 6, issue 4 (2017)) contains three review articles dealing with tocopherols, including their biosynthesis in plants and their metabolism in humans. The journal Prostaglandins & Other Lipid Mediators (Volume 133, November (2017)) is a special issue from the "6th European Workshop on Lipid Mediators" (edited by Bannenberg, G. et al.) with a number of review articles on polyunsaturated fatty acids and oxylipins (eicosanoids and docosanoids).

January 10th, 2018

Although the most important aspect of any new publication is its content, the manner of presentation can make a big difference to how well the message gets across. Text books have lead the way in this regard, but the ability to use colour in diagrams now afforded by many journals has been a considerable step forward, and as more journals go online only I am sure that this facility will be used increasingly. I am also rather envious of those authors who have access to design departments who produce figures and diagrams that are works of art. One new article that meets all these quality criteria deals with phosphoinositides (Choy, C.H. et al. Phosphoinositide diversity, distribution, and effector function: stepping out of the box. Bioessays, 39, 1700121 (2017); DOI). I found this review to be of considerable value in updating my web page here on the topic.

Some years ago, I was rather pleased with myself when my cholesterol level was measured and found to be in the bottom quartile for my age group, but a friend brought me down to earth by telling me that all this meant was that rather than having a heart attack I would probably die of cancer. The editors' selection (and therefore open access) in the latest issue of JBC explains how two isoforms of phospholipase A regulate the nature of the eicosanoids produced during a heart attack and thence the damage done. In non-failing human hearts, one isoform channels arachidonic acid into protective epoxyeicosatrienoic acids (EETs), whereas in failing hearts, activation of a second isoform channels arachidonic acid into toxic hydroxyeicosatetraenoic acids (HETEs) (Moon, S.H. et al. Heart failure-induced activation of phospholipase iPLA2γ generates hydroxyeicosatetraenoic acids opening the mitochondrial permeability transition pore. J. Biol. Chem., 293, 115-129 (2018); DOI). One way or another your lipids probably get you in the end!

January 3rd, 2018

As a New Year gift to lipid analysts, I draw your attention to a 72 page open access publication reviewing NMR spectroscopy (1H, 13C and 31P) of lipids (Alexandri, E. et al. High resolution NMR spectroscopy as a structural and analytical tool for unsaturated lipids in solution. Molecules, 22, 1663 (2017); DOI). It is a large file at 34Mb, so you may need a fast broadband connection.

The lipid A (endotoxin) component of bacterial lipopolysaccharides is a fascinating complex molecule that serves to protect the organism from attack from external agencies, including antibiotics, but is a major reason for the virulence of pathogenic bacteria. Many factors are involved, including the number and nature of the fatty acid constituents, but the general mechanism of the immune response is usually considered to be a binding to a large hydrophobic pocket in a receptor such as toll-like receptor 4 (TLR4) via the lipid chains, while the phosphate groups can interact directly with the receptor leading to formation of a heterodimer complex that is active in immune signalling. However, a new publication demonstrates that the TLR4 receptor does not recognize the endotoxin of a rather nasty pathogen, Francisella novicida, which is thus able to evade the host innate immune system. Instead, this stimulates the cyclooxygenase-2-dependent inflammatory pathway and is responsible for the lethality of such infections through overproduction of proinflammatory effectors such as prostaglandin E2 (Scott, A.J. et al. Host-based lipid inflammation drives pathogenesis in Francisella infection. PNAS, 114, 12596-12601 (2017); DOI).

The regulation of cholesterol levels in animal tissues is a complicated topic involving innumerable factors, and I struggle to come to grips with it. One novel feature that has just come to light is that the first 100 amino acid in a key enzyme in cholesterol biosynthesis, i.e. squalene monooxygenase, is a proteasomal degradation signal or 'degron'. This sequence attaches reversibly to the ER membrane, and in the presence of excessive cholesterol levels, it is ejected and unravels to expose a hydrophobic patch, which then says "eat me" (Chua, N.K. et al. A conserved degron containing an amphipathic helix regulates the cholesterol-mediated turnover of human squalene monooxygenase, a rate-limiting enzyme in cholesterol synthesis. J. Biol. Chem., 292, 19959-19973 (2017); DOI).

December 20th, 2017

Scottish thistle At this time of year, there is only one paper that I wish to highlight because of its appropriateness to the Christmas season, and happily it is open access (Morikawa, T., Matsuda, H. and Yoshikawa, M. A review of anti-inflammatory terpenoids from the incense gum resins frankincense and myrrh. J. Oleo Sci., 66, 805-814 (2017); DOI). It even has three wise men (persons?) as authors. I presume that the word "anti-inflammatory" in the title refers to "Peace on Earth and goodwill to all men".

Merry Christmas and a happy, healthy, prosperous and anti-inflammatory New Year to all my readers!

December 13th, 2017

In recent years, the potential for using natural lipids as pharmaceuticals to treat various disease states has become very evident. Outsiders such as myself are rarely aware of the many pitfalls in taking a new discovery from patent application through to clinical trials and commercial success. A new review discusses this in relation to palmitoylethanolamide and the specialized pro-resolving mediators (Hesselink, J.M.K. Fundamentals of and critical issues in lipid autacoid medicine: a review. Pain Therapy, 6, 153-164 (2017); DOI). For example, palmitoylethanolamide was proven to alleviate neuropathic pain in the 1990s, but the first company to patent and develop this for clinical purposes went out of business because of delays in the Italian licensing system. Now the patents have expired and there is no financial incentive for anyone else to take it on, although there seems little doubt that it is safe and effective. The first patent on the lipoxins was issued in 1984, but only one clinical pilot trial in atopic eczema can be identified so far.

I take some pleasure in reading of natural cholesterol derivatives with important health-giving properties, and one such is dendrogenin A (DDA), a naturally occurring conjugate of cholesterol and histamine. Its synthesis is greatly reduced in cancer cells, and it has now been shown to be a potent tumor suppressor that controls a nuclear receptor to kill cancers (Segala, G. et al. Dendrogenin A drives LXR to trigger lethal autophagy in cancers. Nature Commun., 8, 1903 (2017); DOI - open access).

There is a report in Nature News that Elsevier continues to have a problem with German universities in that negotiations have failed to end a long-term contract dispute. The aim of the universities, which will no doubt be supported by most scientists, is to reduce subscription prices and promote immediate open access. While I accept that commercial publishers must be allowed to make a profit, the last figure I saw for Elsevier was 36% of turnover and this seems grossly excessive. A new business model is surely required. When I read the report, I checked my personal data base of references that are cited in the Literature Survey section of the LipidWeb, and I found that nearly half were to Elsevier journals. This figure is certainly skewed in that I don't have access to many smaller publishers and many of the chemistry journals, not least those from ACS and RSC, but it does demonstrate the influence of Elsevier. If I can't read papers to update my pages here, I rarely cite them, although I do cite those in journals that are sufficiently public spirited to allow open access after 1-2 years.

December 6th, 2017

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

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

November 29th, 2017

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

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

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

November 22nd, 2017

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

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

November 15th, 2017

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

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

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

November 8th, 2017

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

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

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

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

November 1st, 2017

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

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

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

Older entries in this blog are archived for at least a year here..

Author: William W. Christie Updated:March 14th, 2018 Credits/disclaimer LipidWeb logo

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