A LIPID BLOG
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.
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: email@example.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
The 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).
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.
February 5th, 2014
There have been a number of articles in the last year discussing the putative role of palmitoleic acid (9-16:1) as a lipokine – a recently minted word to define a lipid hormone, i.e. it is an adipose tissue-derived molecule, which amongst other effects stimulates the action of insulin in muscle. However, the mechanism and the active form of the metabolite appear unclear. Last April in this blog, I speculated that no one seemed to have connected this with the finding that the family of Wnt proteins, which are central mediators of animal development, with profound influences on adipose tissue amongst other organs, have an unusual and essential acyl modification with palmitoleic acid at a conserved serine residue, at least in murine Wnt-3a, the most intensively studied form (Takada, R. et al. Monounsaturated fatty acid modification of Wnt protein: its role in Wnt secretion. Developmental Cell, 11, 791-801 (2006); DOI: 10.1016/j.devcel.2006.10.003). Recent reviews have discussed both lipokines and Wnt proteins without making this physical connection. Am I being too speculative that this might be behind the mechanism for lipokine action? No one has commented on my suggestion so far.
Column chromatography on silicic acid has been a common means of separating glycolipid and phospholipid fractions from total lipid extracts for more than 50 years - longer than even I have been involved in the analysis of lipids. I have commented in these pages and elsewhere from time that there needed to be a re-appraisal of the methodology with modern adsorbents and with monitoring by modern instrumental methods. I am happy to say that this has now been done, although I can't say that I am surprised that the results are not very encouraging (Heinzelmann, S.M. et al. Critical assessment of glyco- and phospholipid separation by using silica chromatography. Appl. Environm. Microbiol., 80, 360-365 (2014); DOI: 10.1128/AEM.02817-13). The method was applied to microbial samples as opposed to those of animal origin as in the original publication cited, but it is evident that the 'phospholipid' fraction can contain many other non-phospho components, including glycolipids, betaine lipids, and sulfoquinovosyldiacylglycerols. Modifying the conditions provided a relatively small improvement only.
In the days when I was active in research, my colleagues and I tended to favour solid-phase extraction columns and a bonded-amine phase for this type of separation, although recovery of acidic phospholipids was tedious.
January 29th, 2014
As far as I have read, dietary supplementation with DHA has little or no effect on the loss of cognitive ability in the elderly, although there may be health benefits in other areas. I prefer to take my fish oil the natural way in fish. However, it appears that there is plentiful evidence that dietary fish oil is beneficial at the other end of the age scale. It seems to be established that it helps with with behaviour and general school performance, for example. Two new reviews summarize the evidence (Kuratko, C.N. et al. The relationship of docosahexaenoic acid (DHA) with learning and behavior in healthy children: a review. Nutrients, 5, 2777-2810 (2013); DOI: 10.3390/nu5072777. Lane, K.E. and Derbyshire, E. Systematic review of omega-3 enriched foods and health. Brit. Food J., 116, 165-179 (2014); DOI: 10.1108/BFJ-05-2012-0118).
I have commented before on the great advances that have been made possible in the area of plant sphingolipids by modern mass spectrometric methods, especially with respect to the glycosylinositol phosphoceramides, which are now known to be as important as the glycerophospholipids in cell membranes. A new study demonstrates that the overall structures can be very variable across species. Glycosylinositol phosphoceramides in algae differ from those in mosses, gymnosperms and monocots, while dicots contain the greatest complexity. Their composition in the model plant Arabidopsis thaliana is not typical of plant species in general (Cacas, J.-L. et al. Biochemical survey of the polar head of plant glycosylinositolphosphoceramides unravels broad diversity. Phytochemistry, 96, 191-200 (2013); DOI: 10.1016/j.phytochem.2013.08.002).
I have just been reading a useful general review of the biochemistry and function of the oligoglycosphingolipids, which I can recommend, especially as it is open access (D'Angelo, G. et al. Glycosphingolipids: synthesis and functions. FEBS J., 280, 6338-6353 (2013); DOI: 10.1111/febs.12559)
January 22nd, 2014
Issue 24 in December 2013 of FEBS Journal has a number of review articles under the heading of ‘Lipid signalling in health and disease’ edited by Daniela Corda and Maria Antonietta De Matteis. All are open access. I always like articles where the author uses his imagination to speculate on the origin and function of lipids, and I especially enjoyed reading one of these reviews (Michell, R.H. Inositol lipids: from an archaeal origin to phosphatidylinositol 3,5-bisphosphate faults in human disease. FEBS J., 280, 6281-6294 (2013); DOI: 10.1111/febs.12452). It appears that inositol lipids are ubiquitous in the Archaea, but occur only rarely in bacteria and other primitive organism, before assuming major importance in Eukaryotes. This paper lead me to an earlier one on a related topic, which I had missed when it first appeared and discusses how polar head groups that are common to bacteria and Archaea might have evolved (Koga, Y. Early evolution of membrane lipids: how did the lipid divide occur? J. Mol. Evol., 72, 274-282 (2011); DOI: 10.1007/s00239-011-9428-5).
I am continually fascinated by recent discoveries of novel biochemical processes in which lipids are involved. Now it appears that endocannabinoids and lysophosphatidic acid are involved in key aspects of cocaine addiction. It is hoped that interference with the metabolism of these lipids may be of therapeutic value to addicts (Orio, L. et al. Lipid transmitter signaling as a new target for treatment of cocaine addiction: new roles for acylethanolamides and lysophosphatidic acid. Curr. Pharm. Design, 19, 7036-7049 (2013); DOI: 10.2174/138161281940131209143421).
Biochemists may also be interested in an open access review dealing with lipids and the immune system (Dowds, C.M. et al. Lipid antigens in immunity. Biol. Chem., 395, 61-81 (2014); DOI: 10.1515/hsz-2013-0220).
January 15th, 2014
It has long been known that sphingosine-1-phosphate (S1P) promotes cancer proliferation, survival and invasiveness in animal models, while ceramide has the opposite effects. The balance between the two lipids may be critical. This has of course been much more difficult to demonstrate in humans. Strong evidence that this is so has now been obtained in human brain tumours (Abuhusain, H.J. et al. A metabolic shift favoring sphingosine 1-phosphate at the expense of ceramide controls glioblastoma angiogenesis. J. Biol. Chem., 288, 37355-37364 (2013); DOI: 10.1074/jbc.M113.494740). The authors show that “S1P content was, on average, 9-fold higher in glioblastoma tissues compared with normal gray matter, whereas the most abundant form of ceramide in the brain, C18 ceramide, was on average 5-fold lower”. The hope is that inhibitors of sphingosine kinase 1, a key enzyme is S1P biosynthesis, will prove to be effective anti-cancer agents.
The biological function of the related enzyme sphingosine kinase 2 is less well known, but it also is believed to be involved in the development of cancer. A new review discusses the evidence (Neubauer, H.A. and Pitson, S.M. Roles, regulation and inhibitors of sphingosine kinase 2. FEBS J., 280, 5317-5336 (2013); DOI: 10.1111/febs.12314).
While on the subject of sphingolipids, I will have to devote some time to reading a new review on the subject of sphingolipidoses, i.e. storage diseases caused by defects in the catabolism of these complex lipids (Sandhoff, K. Metabolic and cellular bases of sphingolipidoses. Biochem. Soc. Trans., 41, 1562-1568 (2013): DOI: 10.1042/BST20130083).
Perhaps I should take a greater interest in a report highlighted in Science Daily News that “elderly people with high serum vitamin E levels are less likely to suffer from memory disorders than their peers with lower levels”
This is how to teach lipid science - http://m.youtube.com/watch?v=6lrG65DdBl8 - with thanks to Michael Eskin!
January 8th, 2014
The August issue of the journal Molecular Nutrition and Food Research (Volume 57, Issue 8, Pages 1305-1504) was devoted to the topic of ‘Lipidomics: Approaches and Applications in Nutrition Research’ (edited by Claus Schneider).
It has now been revealed that the phospholipid platelet activating factor (PAF) functions as an anti-obesity compound in an animal model (Sugatani, J. et al. Antiobese function of platelet-activating factor: increased adiposity in platelet-activating factor receptor-deficient mice with age. FASEB J., 28, 440-452 (2014); DOI: 10.1096/fj.13-233262). The lipid operates in this way through stimulation of its receptor in brown but not white adipose tissue. It appears that reduction of this activity may be responsible for increasing fat deposition as we age. The story made our national press in the U.K., and there is an interesting report on the Science Daily News website.
Until recently, it was believed that approximately 90% of cholesterol elimination from the body occurred via bile acids in humans. However, experiments with animal models now suggest that a significant amount may be secreted directly into the intestines by a process known as trans-intestinal cholesterol efflux. How this occurs and its relevance to humans are obviously of considerable clinical importance and are under active investigation. A new review in an open access journal summarises what is known (Jakulj, L. et al. Intestinal cholesterol secretion: future clinical implications. Neth. J. Med., 71, 459-465 (2013); (www.njmonline.nl/getpdf.php?t=a&id=10001021).
December 25th, 2013
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: 10.1039/C3AY41344F).
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: 10.1111/febs.12374). 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.
Past items are archived for about a year here..
James Hutton Institute (and Mylnefield Lipid Analysis), Invergowrie, Dundee (DD2 5DA), Scotland.
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