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Society News
ARTICLE IN PRESS
Prostaglandins, Leukotrienes and Essential Fatty Acids 78 (2008) 231–236 www.elsevier.com/locate/plefa
ISSFAL Society Section
Society News
Since PLEFA became the official journal of ISSFAL, we thought of maintaining the tradition of having selected papers commented by experts in the field, so that you readers can rapidly grasp and interpret the most recent outcomes in the area of fatty acids and lipids. This newsletter is still work-in-progress, other experts are being recruited and your suggestions and comments are, as always, very welcome. You will be reading this just after our ISSFAL 2008 meeting in Kansas City (a detailed report will be published). This is the best time to turn excitement intoy membership. Talk about ISSFAL to your friends and colleagues and make sure you include free
0952-3278/$ - see front matter doi:10.1016/j.plefa.2008.05.001
subscription to PLEFA in your talk. Growing strong as a Society also means wider membership, so remember: the more the merrier! With such bonuses such as discounted registration to meetings, PLEFA subscription, established networks of scientists and corporate experts, and a newsletter, our membership rate is well worth. Once again, please let us have your comments on how to further develop this section. In the meantime, enjoy reading it! Francesco Visioli Universite´ Pierre et Marie Curie, Paris VI, Paris, France.
ARTICLE IN PRESS 232
Society News / Prostaglandins, Leukotrienes and Essential Fatty Acids 78 (2008) 231–236
Fatty acids and heart disease By Bill Harris, South Dakota Health Research Foundation A reduced susceptibility to cardiac arrhythmias has become the favored mechanism of action to explain the cardioprotective effects of omega-3 fatty acids. That hypothesis received significant support from two recent publications, one epidemiological and the other interventional. Mozaffarian et al. examined a variety of indicators of heart rate variability (HRV) derived from 24-h Holter monitoring in the 1152 participants in the Cardiovascular Health Study, a prospective cohort study of Americans 464 years of age. They correlated HRV markers of autonomic function with the reported intake of tuna or other baked/broiled fish (which has been correlated with plasma EPA and DHA levels in earlier reports). They found that higher intakes of fish were significantly associated with markers of improved HRV, including greater vagal predominance, moderated baroreceptor responses, and improved sinoatrial node function. These observations are consistent with the reduced risk for cardiovascular disease associated with higher intakes of ‘‘oily’’ fish previously reported in this cohort. Consistent with the findings of Mozaffarian et al. are those recently reported by Metcalfe and colleagues from Adelaide. This group evaluated the antiarrhythmic effect of dietary fish oil on the inducibility of ventricular tachycardia (VT) in patients at high risk of sudden cardiac death (SCD). They randomised patients with coronary artery disease undergoing defibrillator implantation (if VT was inducible at baseline) to either a test group which took 900 mg of EPA+DHA/d or to an unsupplemented control group (why no placebo was used is unclear). VT inducibility was retested after 6 weeks of treatment. They reported that VT was more difficult to induce after 6 weeks of treatment than at baseline in the omega-3 group whereas no change in inducibility was observed in the control group. These changes were highly correlated with increases in RBC EPA and DHA content. The findings of Metcalfe et al. and Mozaffarian et al. both support the hypothesis that higher tissue levels of omega-3 fatty acids reduce the susceptibility of the myocardium to develop fatal arrhythmias, and they strengthen the case for recommending increased intakes of EPA and DHA in order to reduce morbidity and mortality from cardiovascular disease.
References D. Mozaffarian, P.K. Stein, R.J. Prineas, D.S. Siscovick, Dietary fish and omega-3 fatty acid con-
sumption and heart rate variability in US adults, Circulation 17 (2008) 1130–1137. R.G. Metcalf, P. Sanders, M.J. James, L.G. Cleland, G.D. Young. Effect of dietary n-3 polyunsaturated fatty acids on the inducibility of ventricular tachycardia in patients with ischemic cardiomyopathy. Am. J. Cardiol. 101 (2008) 758–761.
Saturated and trans fatty acids and human health By Peter Zock, Unilever, The Netherlands Two dietary trials reported in the March AJCN issue directly investigated the effects on cardiovascular risk factors of dairy (ruminant) trans fatty acids (TFA) versus industrial TFA. Both studies applied a randomised cross-over design, had a good control over dietary intake, and were well-conducted. Duration per study diet was 3–4 weeks. In the TRANSFACT study, Chardigny and colleagues compared in a group of 19 men and 21 women the effects of two diets: one high in ruminant TFA and the other high in industrial TFA, with a difference in the two types of TFA of about 5% of energy. TRANSFACT did not include a low-TFA control diet. The ruminant TFA diet resulted in higher HDL cholesterol, LDL cholesterol, and triglyceride levels than the industrial TFA diet in the women, but not in the men. The ratio of total to HDL cholesterol was not significantly different between the diets for either gender. Motard-Belanger and colleagues compared in 38 men the effects of a high-industrial TFA diet with those of a high-ruminant TFA diet (both 3.7% of energy), and also with a lower-ruminant TFA (1.5% of energy) diet and a low total TFA (0.8% of energy) control diet. Both the industrial TFA diet and the high-ruminant TFA diet (3.7% of energy) increased LDL cholesterol and the ratio of total to HDL cholesterol, and decreased HDL cholesterol compared with the two lower-TFA diets. The lower-dairy TFA diet did not have significant effects as compared with the low-TFA control diet. Comment In the accompanying Editorial, Willett and Mozaffarian point out that the possible differential effect of dairy and industrial TFA on cardiovascular risk is not a critical public health or policy issue. In epidemiologic studies, TFA intake from natural (ruminant) sources, in actual amounts consumed in real-life diets did not show a positive relation with the risk of coronary heart disease. In practice, adherence to guidelines for saturated fat intake will ensure low total consumption of ruminant TFA,
ARTICLE IN PRESS Society News / Prostaglandins, Leukotrienes and Essential Fatty Acids 78 (2008) 231–236
because dairy and ruminant meat fats, the single dietary sources of ruminant TFA, are very high in saturated fatty acids. Willett and Mozaffarian take the position that although small differences in metabolic effects between industrial and ruminant TFA remain possible, at present there is no compelling evidence to exclude natural TFA from the total TFA on food labels. In TRANSFACT, differential effects were only seen in women, and not in men. There is no clear explanation for this. In the women, both LDL and HDL cholesterol were higher after the dairy TFA diet, resulting in a net about similar effect on the blood lipid risk profile. The study by Motard-Belanger showed similar adverse effects on blood lipids and lipoproteins of industrial TFA and dairy TFA at 3.7% of daily energy intake. The lower-dairy TFA diet showed no effects, but the difference in TFA intake between the lower-dairy TFA and the reference low-TFA diet was only 0.7% of energy, and it is unlikely that the study had sufficient statistical power to detect the small effects on blood lipids and lipoproteins expected with such a low difference in intake. There are no good mechanistic hypotheses on how ruminant TFA could have effects on CVD risk different from those of industrial TFA. Also, the lack of association between ruminant TFA and CVD in epidemiological studies can not be taken as strong evidence to support that ruminant and industrial TFA have different effects on CVD risk. Nevertheless, it shows that the contribution of ruminant TFA to risk at actual intake levels is not large. Whether there are any differential effects of industrial and ruminant TFA on CVD risk markers can only be sorted out by further controlled human intervention studies. However, the public health relevance of potential differences is limited. It should be noted that diets relatively high in ruminant TFA are inevitably high in saturated fatty acids. Because of its much higher levels of intake, saturated fat intake is a more important public health issue than ruminant TFA intake. These new studies together with earlier published evidence do not provide clear indications for a difference in health effects between trans fatty acids from dairy (ruminant) fat and those from partially hydrogenated vegetable oils. Although the actual level of ruminant TFA consumption in the population is not high, it is at present reasonable and prudent to assume that ruminant and industrial TFA have similar detrimental effects on health.
References J.-M. Chardigny, F. Destaillats, C. MalpuechBrugere, et al., Do industrially-produced and natural trans fatty acid sources have the same impact on cardiovascular disease risk factors in healthy subjects? Results of the trans Fatty Acids Collaboration (TRANSFACT) study, Am. J. Clin. Nutr. 87 (2008) 558–566.
233
I. Motard-Be´langer, A. Charest, G. Grenier, et al., Study of the effect of trans fatty acids from ruminants on blood lipids and other risk factors for cardiovascular disease, Am. J. Clin. Nutr. 87 (2008) 593–599. W. Willett, D. Mozaffarian, Ruminant or industrial sources of trans fatty acids: public health issue or food label skirmish (Editorial), Am. J. Clin. Nutr. 87 (2008) 515–516.
Fatty acids and cancer By Laura Jenski, University of South Dakota, USA Excitement surrounds new original articles that appear on hot topics, yet we all appreciate the hard work and enduring value of review articles on complex and rapidly changing subjects. In the last few months, two review articles have appeared, electronically or in hard copy, that are important for our progress in research on lipids or fatty acids and cancer. Each review article has its own special strength, and aids us in different ways to understand the tumour promoting or suppressing activities of lipids. The first review is ‘‘Human Biochemistry of the Isoprostane Pathway’’ authored by Ginger L. Milne, Huiyong Yin, and Jason D. Morrow of Vanderbilt University School of Medicine, and published in the Journal of Biological Chemistry (published online on February 19, 2008, as manuscript R700047200). This article provides an easily readable text of the detailed nomenclature and synthesis of isoprostanes, written by the laboratory that discovered isoprostanes in 1990. As noted by the authors, isoprostanes are produced by freeradical catalysed peroxidation of fatty acids including arachidonic acid (n-6), eicosapentaenoic acid (EPA, n-3) and docosahexaenoic acid (DHA, n-3). A variety of regioisomers of different isoprostanes are formed by free-radical attack on lipids, and the differential propensity of different isomers to undergo further oxidation determines their ultimate levels in tissues and fluids. The authors review isoprostane detection methods, which differ greatly in their ease and accuracy. However, clearly it is possible to gather accurate isoprostane levels from a variety of normal and diseases conditions, thus making isoprostanes an enormously valuable biomarker of oxidative stress in vivo. Of the F2isoprostanes produced from arachidonic acid, several are associated with biological activities including vasoconstriction, endothelin release and vascular smooth muscle proliferation, inhibition of platelet aggregation, and activation of the PGF2a receptor. Of critical importance is the observation that isoprostanes are produced from EPA and DHA, and that addition of EPA to the diet reduced the production of proinflammatory
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Society News / Prostaglandins, Leukotrienes and Essential Fatty Acids 78 (2008) 231–236
isoprostanes from arachidonic acid, thus raising speculation that n-3 fatty acids have beneficial effects in a variety of diseases from atherosclerosis and neurodegenerative diseases to cancer through modulation of isoprostane production. The second review is ‘‘Dietary fat-gene interactions in cancer’’ by Yong Q. Cheng, et al. from Wake Forest University School of Medicine, published in Cancer Metastasis Rev (2007) 26: 535–551. Unlike the previous review, which is focused tightly on isoprostane chemistry and biological activities, this article provides a broad range of information on the potential roles for dietary lipids in cancer promotion or prevention, and the potential for genetic constitution to influence these roles. Thus, the review provides an introduction to fatty acid synthesis and its regulation, and a range of evidence implicating saturated and n-6 polyunsaturated fatty acids in cancer progression. One of the strengths of the article is its provision of various mechanisms for fatty acid modulation of cancer, from lipid raft alteration and protein prenylation to modulation of cyclooxygenase-2 activity. The detailed descriptions of diet–gene interactions are somewhat limited in this review, but are used to underscore the variation in clinical and experimental results investigators have observed with genetically distinct individuals. As in the article described above, considerable emphasis is placed on the disparate actions of n-3 and n-6 fatty acids across a broad range of biological activities. Thus, we appreciate the differing functions of n-3 and n-6 fatty acids, and the potential disparity of their actions in cancer, but it is clear that much is to be learned. These two recent reviews provide well written and easily understandable summaries and opinions on the behaviours of fatty acids in cancer.
Fatty acids and neurochemistry By Eric Murphy, University of North Dakota, USA I’ll be focusing the neurochemistry section on our close and dear friend, 22:6n-3. The first paper of discussion is from the Spector group and demonstrates that hippocampal neurons have the ability to elongate shorter chain n-3 fatty acids to 22:6n-3. As expected, incorporation rates for 22:6n-3 are higher than the combined elongation/desaturation and incorporation of 18:3n-3 or 20:5n-3 into phospholipid pools. This makes perfect sense from a metabolism viewpoint and is consistent with feeding studies by our lab and others that show 18:3n-3 enriched diets will increase brain 22:6n-3 mass in vivo, but not to the same extent as feeding high 22:6n-3 containing diets. In their pioneering work, the Spector laboratory also demonstrated years
ago that astrocytes elongate 18:3n-3 to 22:6n-3. This discovery led to the idea that astrocytes were the primary sources of endogenous 22:6n-3 formation in the central nervous system (1). In another previous paper, the Spector laboratory demonstrated that cortical and cerebellar neurons are not capable of elongating/ desaturating 18:3n-3 to 22:6n-3 (1). Hence, this new work is quite exciting in that it demonstrates that the hippocampal neuron is adept at metabolising 18:3n-3 into 22:6n-3. The importance of this work is that the hippocampus is a brain region critical in learning and memory, thus this work may have downstream clinical implications for diseases such as Alzheimer’s disease. Beside formation of 22:6n-3 from 18:3n-3, this paper also demonstrates formation of 20:4n-6 from 18:2n-6, again consistent with elongation/desaturation of 18:2n-6 to 20:4n-6 in astrocytes, which was not observed in cortical and cerebellar neurons. One caveat is that the hippocampal cells used herein had a low level of 22:6n-3, hence there might be an upregulation of biosynthesis of 22:6n-3 from 18:3n-3 in these cells. Nonetheless, this work is quite exciting and adds more fuel to this controversial area, yet to me represents an important advance in our understanding of brain n-3 fatty acid metabolism. The second paper is from the Yavin group and demonstrates the importance of 22:6n-3 in modulating incorporation of iron into oligodendroglial-like cells. This process was evident more so for 22:6n-3 than for 20:4n-6. It is important to note that incubating cells in concentrations of 20:4n-6 or 22:6n-3 much above 5 mM induced cell death, with cell viability reduced to 55% at 25 mM. [Note that the fatty acids were given directly to the cells in an unesterified, unbound form, but that the concentrations were below the critical micelle concentration.] More importantly, 22:6n-3 increased cell death in the presence of increasing amounts of iron as well as increased incorporation of iron presumably via the upregulation of the iron transport protein, DMT-1, while 20:4n-6 had no effect on DMT-1 or iron incorporation. At low levels of iron (5 mM), DHA potentiates the iron induced increase in glutathione peroxidase and glutathione reductase activity, while DHA alone increase glutathione peroxidase activity. However, it is interesting that low levels of iron promoted an increase in ethanolamine glycerophospholipid in the exofacial leaflet of the membrane, which the authors suggest is operative in signaling changes in gene transcription in the nucleus. There are several caveats to this paper. First, the authors did not determine how much 20:4n-6 or 22:6n-3 was incorporated into the cellular lipid pools. Second, the authors did not establish if indeed the cells were n-6 or n-3 fatty acid poor, which could alter the impact of 22:6n-3 on gene transcription. Thus, this paper demonstrates a connection to iron transport via the upregulation of
ARTICLE IN PRESS Society News / Prostaglandins, Leukotrienes and Essential Fatty Acids 78 (2008) 231–236
DMT-1 expression as well as an increase in the glutathione oxidative protection cascade in oligodendroglia-like cells. References S.A. Moore, E. Yoder, S. Murphy, G.R. Dutton, A.A. Spector, Astrocytes, not neurons, produce docosahexaenoic acid (22:6n-3) and arachidonic acid (20:4n-6). J. Neurochem. 56 (1991) 518–524.
235
T.L. Kaduce, Y. Chen, J.W. Hell, A.A. Spector, Docosahexaenoic acid synthesis from n-3 precursors in rat hippocampal slices. J. Neurochem. 105 (2008) 1525– 1535. A. Brand, E. Schonfeld, I. Isharel, E. Yavin, Docosahexaenoic acid-dependent iron accumulation in oligodendroglia cells protects from hydrogen peroxide-induce damage. J. Neurochem. 105 (2008) 1325–1335.
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Society News / Prostaglandins, Leukotrienes and Essential Fatty Acids 78 (2008) 231–236
The view from the Secretary’s Perch If past experience is any guide, this July issue of PLEFA will appear some time in August, when most ISSFAL members will be on a no-doubt well earned break. So it will be waiting to be read when they return in September, recharged and re-energised. As I write this now, the final preparations for our congress in Kansas City are being made, and we are preparing to welcome around 500 people to a 5 day ‘‘festival of science’’ as it was described by one delighted delegate at our 2006 congress in Cairns. The ISSFAL congresses are certainly major activities for the Society, and take a lot of organising, a lot of support from our Corporate members and others, and a lot of input from our members. At the Kansas City meeting for example, we will have had more than 400 poster and oral presentations, as well as some 20 plenary lectures delivered by people who are world leaders in research in their fields. We will also have recognised the contributions to our field and our Society made by Alex Leaf Award winner Art Spector, as well as encouraged research in our field by awarding the $4500 Early Career Award to Richard Bazinet. In addition to all this, the ISSFAL 2008 organisers will have done their bit, by encouraging 63 New Investigators with free registrations and help with accommodation costs, plus the giving away of nine $500 laptops to those NI’s judged to have given the best presentations. But no doubt more on this will appear in the report from the Congress which our Newsletter Editor Francesco will be writing for the next issue. From the point of view of the Society, things are going very well, as my report to the members at Kansas City will have revealed. We now have more than 550 members paid up for either 2007 or 2008, and have processed a record number of new members this year, more than 110 so far, and we have a record number of Corporate members, 21 at present. The new (November 2006) website is getting a lot of hits (more than 60,000 per year), and generally seems to be well received, and provides members, among other facilities, with the ability to check on their dues status, which the old one did not do. For those not present at Kansas City, the minutes from the Business meeting will eventually
appear in the member-only section of the website, so you can catch up with what was said there. The abstracts from the meeting will also in due course appear in the Archive section of the website, but it will no doubt take me several months to get this mammoth task completed. The next big issue facing the Society is the election of a Vice-President and President Elect to take over from Philip Calder when he is elevated to the role of President in March 2009. At that time our current President Michel Lagarde will stand down as President, and take over the role of Past-President from Norman Salem Jnr. Norman will finally bow out of the ISSFAL Executive after his 9 year stint; I am sure I will be echoing the words of President Michel in paying tribute to the dedicated work put in by Norman during his time on the Executive. We must therefore seek nominations for the role of Vice-President and President Elect for the election which will be carried out early in 2009. Please send in nominations to me at [email protected]. I plan to mail ballot forms out in January, along with dues reminders for those that are not already paid for 2009. I should point out that we have now already more than 20 members that have paid up for 2009, so I would encourage you all to become members of the ‘‘2009 paid-up club’’ as soon as you can; I realise how easy it is to put it off, and before you know it, you end up running into arrears, or even worse, having your access to the Society terminated! Another change facing the Society is that my own final term of office expires in 2010, and the search will soon be under way for my replacement. If anyone is interested, or knows someone that might be interested in applying, please e-mail me, and I will pass the details along to the search sub-committee. I trust your summer break will have been invigorating (if you had one!) and that you will be ready to tackle the challenges ahead with renewed vigour.
Ray Rice Secretary/Treasurer, ISSFAL
Prostaglandins, Leukotrienes and Essential Fatty Acids 78 (2008) 231–236 www.elsevier.com/locate/plefa
ISSFAL Society Section
Society News
Since PLEFA became the official journal of ISSFAL, we thought of maintaining the tradition of having selected papers commented by experts in the field, so that you readers can rapidly grasp and interpret the most recent outcomes in the area of fatty acids and lipids. This newsletter is still work-in-progress, other experts are being recruited and your suggestions and comments are, as always, very welcome. You will be reading this just after our ISSFAL 2008 meeting in Kansas City (a detailed report will be published). This is the best time to turn excitement intoy membership. Talk about ISSFAL to your friends and colleagues and make sure you include free
0952-3278/$ - see front matter doi:10.1016/j.plefa.2008.05.001
subscription to PLEFA in your talk. Growing strong as a Society also means wider membership, so remember: the more the merrier! With such bonuses such as discounted registration to meetings, PLEFA subscription, established networks of scientists and corporate experts, and a newsletter, our membership rate is well worth. Once again, please let us have your comments on how to further develop this section. In the meantime, enjoy reading it! Francesco Visioli Universite´ Pierre et Marie Curie, Paris VI, Paris, France.
ARTICLE IN PRESS 232
Society News / Prostaglandins, Leukotrienes and Essential Fatty Acids 78 (2008) 231–236
Fatty acids and heart disease By Bill Harris, South Dakota Health Research Foundation A reduced susceptibility to cardiac arrhythmias has become the favored mechanism of action to explain the cardioprotective effects of omega-3 fatty acids. That hypothesis received significant support from two recent publications, one epidemiological and the other interventional. Mozaffarian et al. examined a variety of indicators of heart rate variability (HRV) derived from 24-h Holter monitoring in the 1152 participants in the Cardiovascular Health Study, a prospective cohort study of Americans 464 years of age. They correlated HRV markers of autonomic function with the reported intake of tuna or other baked/broiled fish (which has been correlated with plasma EPA and DHA levels in earlier reports). They found that higher intakes of fish were significantly associated with markers of improved HRV, including greater vagal predominance, moderated baroreceptor responses, and improved sinoatrial node function. These observations are consistent with the reduced risk for cardiovascular disease associated with higher intakes of ‘‘oily’’ fish previously reported in this cohort. Consistent with the findings of Mozaffarian et al. are those recently reported by Metcalfe and colleagues from Adelaide. This group evaluated the antiarrhythmic effect of dietary fish oil on the inducibility of ventricular tachycardia (VT) in patients at high risk of sudden cardiac death (SCD). They randomised patients with coronary artery disease undergoing defibrillator implantation (if VT was inducible at baseline) to either a test group which took 900 mg of EPA+DHA/d or to an unsupplemented control group (why no placebo was used is unclear). VT inducibility was retested after 6 weeks of treatment. They reported that VT was more difficult to induce after 6 weeks of treatment than at baseline in the omega-3 group whereas no change in inducibility was observed in the control group. These changes were highly correlated with increases in RBC EPA and DHA content. The findings of Metcalfe et al. and Mozaffarian et al. both support the hypothesis that higher tissue levels of omega-3 fatty acids reduce the susceptibility of the myocardium to develop fatal arrhythmias, and they strengthen the case for recommending increased intakes of EPA and DHA in order to reduce morbidity and mortality from cardiovascular disease.
References D. Mozaffarian, P.K. Stein, R.J. Prineas, D.S. Siscovick, Dietary fish and omega-3 fatty acid con-
sumption and heart rate variability in US adults, Circulation 17 (2008) 1130–1137. R.G. Metcalf, P. Sanders, M.J. James, L.G. Cleland, G.D. Young. Effect of dietary n-3 polyunsaturated fatty acids on the inducibility of ventricular tachycardia in patients with ischemic cardiomyopathy. Am. J. Cardiol. 101 (2008) 758–761.
Saturated and trans fatty acids and human health By Peter Zock, Unilever, The Netherlands Two dietary trials reported in the March AJCN issue directly investigated the effects on cardiovascular risk factors of dairy (ruminant) trans fatty acids (TFA) versus industrial TFA. Both studies applied a randomised cross-over design, had a good control over dietary intake, and were well-conducted. Duration per study diet was 3–4 weeks. In the TRANSFACT study, Chardigny and colleagues compared in a group of 19 men and 21 women the effects of two diets: one high in ruminant TFA and the other high in industrial TFA, with a difference in the two types of TFA of about 5% of energy. TRANSFACT did not include a low-TFA control diet. The ruminant TFA diet resulted in higher HDL cholesterol, LDL cholesterol, and triglyceride levels than the industrial TFA diet in the women, but not in the men. The ratio of total to HDL cholesterol was not significantly different between the diets for either gender. Motard-Belanger and colleagues compared in 38 men the effects of a high-industrial TFA diet with those of a high-ruminant TFA diet (both 3.7% of energy), and also with a lower-ruminant TFA (1.5% of energy) diet and a low total TFA (0.8% of energy) control diet. Both the industrial TFA diet and the high-ruminant TFA diet (3.7% of energy) increased LDL cholesterol and the ratio of total to HDL cholesterol, and decreased HDL cholesterol compared with the two lower-TFA diets. The lower-dairy TFA diet did not have significant effects as compared with the low-TFA control diet. Comment In the accompanying Editorial, Willett and Mozaffarian point out that the possible differential effect of dairy and industrial TFA on cardiovascular risk is not a critical public health or policy issue. In epidemiologic studies, TFA intake from natural (ruminant) sources, in actual amounts consumed in real-life diets did not show a positive relation with the risk of coronary heart disease. In practice, adherence to guidelines for saturated fat intake will ensure low total consumption of ruminant TFA,
ARTICLE IN PRESS Society News / Prostaglandins, Leukotrienes and Essential Fatty Acids 78 (2008) 231–236
because dairy and ruminant meat fats, the single dietary sources of ruminant TFA, are very high in saturated fatty acids. Willett and Mozaffarian take the position that although small differences in metabolic effects between industrial and ruminant TFA remain possible, at present there is no compelling evidence to exclude natural TFA from the total TFA on food labels. In TRANSFACT, differential effects were only seen in women, and not in men. There is no clear explanation for this. In the women, both LDL and HDL cholesterol were higher after the dairy TFA diet, resulting in a net about similar effect on the blood lipid risk profile. The study by Motard-Belanger showed similar adverse effects on blood lipids and lipoproteins of industrial TFA and dairy TFA at 3.7% of daily energy intake. The lower-dairy TFA diet showed no effects, but the difference in TFA intake between the lower-dairy TFA and the reference low-TFA diet was only 0.7% of energy, and it is unlikely that the study had sufficient statistical power to detect the small effects on blood lipids and lipoproteins expected with such a low difference in intake. There are no good mechanistic hypotheses on how ruminant TFA could have effects on CVD risk different from those of industrial TFA. Also, the lack of association between ruminant TFA and CVD in epidemiological studies can not be taken as strong evidence to support that ruminant and industrial TFA have different effects on CVD risk. Nevertheless, it shows that the contribution of ruminant TFA to risk at actual intake levels is not large. Whether there are any differential effects of industrial and ruminant TFA on CVD risk markers can only be sorted out by further controlled human intervention studies. However, the public health relevance of potential differences is limited. It should be noted that diets relatively high in ruminant TFA are inevitably high in saturated fatty acids. Because of its much higher levels of intake, saturated fat intake is a more important public health issue than ruminant TFA intake. These new studies together with earlier published evidence do not provide clear indications for a difference in health effects between trans fatty acids from dairy (ruminant) fat and those from partially hydrogenated vegetable oils. Although the actual level of ruminant TFA consumption in the population is not high, it is at present reasonable and prudent to assume that ruminant and industrial TFA have similar detrimental effects on health.
References J.-M. Chardigny, F. Destaillats, C. MalpuechBrugere, et al., Do industrially-produced and natural trans fatty acid sources have the same impact on cardiovascular disease risk factors in healthy subjects? Results of the trans Fatty Acids Collaboration (TRANSFACT) study, Am. J. Clin. Nutr. 87 (2008) 558–566.
233
I. Motard-Be´langer, A. Charest, G. Grenier, et al., Study of the effect of trans fatty acids from ruminants on blood lipids and other risk factors for cardiovascular disease, Am. J. Clin. Nutr. 87 (2008) 593–599. W. Willett, D. Mozaffarian, Ruminant or industrial sources of trans fatty acids: public health issue or food label skirmish (Editorial), Am. J. Clin. Nutr. 87 (2008) 515–516.
Fatty acids and cancer By Laura Jenski, University of South Dakota, USA Excitement surrounds new original articles that appear on hot topics, yet we all appreciate the hard work and enduring value of review articles on complex and rapidly changing subjects. In the last few months, two review articles have appeared, electronically or in hard copy, that are important for our progress in research on lipids or fatty acids and cancer. Each review article has its own special strength, and aids us in different ways to understand the tumour promoting or suppressing activities of lipids. The first review is ‘‘Human Biochemistry of the Isoprostane Pathway’’ authored by Ginger L. Milne, Huiyong Yin, and Jason D. Morrow of Vanderbilt University School of Medicine, and published in the Journal of Biological Chemistry (published online on February 19, 2008, as manuscript R700047200). This article provides an easily readable text of the detailed nomenclature and synthesis of isoprostanes, written by the laboratory that discovered isoprostanes in 1990. As noted by the authors, isoprostanes are produced by freeradical catalysed peroxidation of fatty acids including arachidonic acid (n-6), eicosapentaenoic acid (EPA, n-3) and docosahexaenoic acid (DHA, n-3). A variety of regioisomers of different isoprostanes are formed by free-radical attack on lipids, and the differential propensity of different isomers to undergo further oxidation determines their ultimate levels in tissues and fluids. The authors review isoprostane detection methods, which differ greatly in their ease and accuracy. However, clearly it is possible to gather accurate isoprostane levels from a variety of normal and diseases conditions, thus making isoprostanes an enormously valuable biomarker of oxidative stress in vivo. Of the F2isoprostanes produced from arachidonic acid, several are associated with biological activities including vasoconstriction, endothelin release and vascular smooth muscle proliferation, inhibition of platelet aggregation, and activation of the PGF2a receptor. Of critical importance is the observation that isoprostanes are produced from EPA and DHA, and that addition of EPA to the diet reduced the production of proinflammatory
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isoprostanes from arachidonic acid, thus raising speculation that n-3 fatty acids have beneficial effects in a variety of diseases from atherosclerosis and neurodegenerative diseases to cancer through modulation of isoprostane production. The second review is ‘‘Dietary fat-gene interactions in cancer’’ by Yong Q. Cheng, et al. from Wake Forest University School of Medicine, published in Cancer Metastasis Rev (2007) 26: 535–551. Unlike the previous review, which is focused tightly on isoprostane chemistry and biological activities, this article provides a broad range of information on the potential roles for dietary lipids in cancer promotion or prevention, and the potential for genetic constitution to influence these roles. Thus, the review provides an introduction to fatty acid synthesis and its regulation, and a range of evidence implicating saturated and n-6 polyunsaturated fatty acids in cancer progression. One of the strengths of the article is its provision of various mechanisms for fatty acid modulation of cancer, from lipid raft alteration and protein prenylation to modulation of cyclooxygenase-2 activity. The detailed descriptions of diet–gene interactions are somewhat limited in this review, but are used to underscore the variation in clinical and experimental results investigators have observed with genetically distinct individuals. As in the article described above, considerable emphasis is placed on the disparate actions of n-3 and n-6 fatty acids across a broad range of biological activities. Thus, we appreciate the differing functions of n-3 and n-6 fatty acids, and the potential disparity of their actions in cancer, but it is clear that much is to be learned. These two recent reviews provide well written and easily understandable summaries and opinions on the behaviours of fatty acids in cancer.
Fatty acids and neurochemistry By Eric Murphy, University of North Dakota, USA I’ll be focusing the neurochemistry section on our close and dear friend, 22:6n-3. The first paper of discussion is from the Spector group and demonstrates that hippocampal neurons have the ability to elongate shorter chain n-3 fatty acids to 22:6n-3. As expected, incorporation rates for 22:6n-3 are higher than the combined elongation/desaturation and incorporation of 18:3n-3 or 20:5n-3 into phospholipid pools. This makes perfect sense from a metabolism viewpoint and is consistent with feeding studies by our lab and others that show 18:3n-3 enriched diets will increase brain 22:6n-3 mass in vivo, but not to the same extent as feeding high 22:6n-3 containing diets. In their pioneering work, the Spector laboratory also demonstrated years
ago that astrocytes elongate 18:3n-3 to 22:6n-3. This discovery led to the idea that astrocytes were the primary sources of endogenous 22:6n-3 formation in the central nervous system (1). In another previous paper, the Spector laboratory demonstrated that cortical and cerebellar neurons are not capable of elongating/ desaturating 18:3n-3 to 22:6n-3 (1). Hence, this new work is quite exciting in that it demonstrates that the hippocampal neuron is adept at metabolising 18:3n-3 into 22:6n-3. The importance of this work is that the hippocampus is a brain region critical in learning and memory, thus this work may have downstream clinical implications for diseases such as Alzheimer’s disease. Beside formation of 22:6n-3 from 18:3n-3, this paper also demonstrates formation of 20:4n-6 from 18:2n-6, again consistent with elongation/desaturation of 18:2n-6 to 20:4n-6 in astrocytes, which was not observed in cortical and cerebellar neurons. One caveat is that the hippocampal cells used herein had a low level of 22:6n-3, hence there might be an upregulation of biosynthesis of 22:6n-3 from 18:3n-3 in these cells. Nonetheless, this work is quite exciting and adds more fuel to this controversial area, yet to me represents an important advance in our understanding of brain n-3 fatty acid metabolism. The second paper is from the Yavin group and demonstrates the importance of 22:6n-3 in modulating incorporation of iron into oligodendroglial-like cells. This process was evident more so for 22:6n-3 than for 20:4n-6. It is important to note that incubating cells in concentrations of 20:4n-6 or 22:6n-3 much above 5 mM induced cell death, with cell viability reduced to 55% at 25 mM. [Note that the fatty acids were given directly to the cells in an unesterified, unbound form, but that the concentrations were below the critical micelle concentration.] More importantly, 22:6n-3 increased cell death in the presence of increasing amounts of iron as well as increased incorporation of iron presumably via the upregulation of the iron transport protein, DMT-1, while 20:4n-6 had no effect on DMT-1 or iron incorporation. At low levels of iron (5 mM), DHA potentiates the iron induced increase in glutathione peroxidase and glutathione reductase activity, while DHA alone increase glutathione peroxidase activity. However, it is interesting that low levels of iron promoted an increase in ethanolamine glycerophospholipid in the exofacial leaflet of the membrane, which the authors suggest is operative in signaling changes in gene transcription in the nucleus. There are several caveats to this paper. First, the authors did not determine how much 20:4n-6 or 22:6n-3 was incorporated into the cellular lipid pools. Second, the authors did not establish if indeed the cells were n-6 or n-3 fatty acid poor, which could alter the impact of 22:6n-3 on gene transcription. Thus, this paper demonstrates a connection to iron transport via the upregulation of
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DMT-1 expression as well as an increase in the glutathione oxidative protection cascade in oligodendroglia-like cells. References S.A. Moore, E. Yoder, S. Murphy, G.R. Dutton, A.A. Spector, Astrocytes, not neurons, produce docosahexaenoic acid (22:6n-3) and arachidonic acid (20:4n-6). J. Neurochem. 56 (1991) 518–524.
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T.L. Kaduce, Y. Chen, J.W. Hell, A.A. Spector, Docosahexaenoic acid synthesis from n-3 precursors in rat hippocampal slices. J. Neurochem. 105 (2008) 1525– 1535. A. Brand, E. Schonfeld, I. Isharel, E. Yavin, Docosahexaenoic acid-dependent iron accumulation in oligodendroglia cells protects from hydrogen peroxide-induce damage. J. Neurochem. 105 (2008) 1325–1335.
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The view from the Secretary’s Perch If past experience is any guide, this July issue of PLEFA will appear some time in August, when most ISSFAL members will be on a no-doubt well earned break. So it will be waiting to be read when they return in September, recharged and re-energised. As I write this now, the final preparations for our congress in Kansas City are being made, and we are preparing to welcome around 500 people to a 5 day ‘‘festival of science’’ as it was described by one delighted delegate at our 2006 congress in Cairns. The ISSFAL congresses are certainly major activities for the Society, and take a lot of organising, a lot of support from our Corporate members and others, and a lot of input from our members. At the Kansas City meeting for example, we will have had more than 400 poster and oral presentations, as well as some 20 plenary lectures delivered by people who are world leaders in research in their fields. We will also have recognised the contributions to our field and our Society made by Alex Leaf Award winner Art Spector, as well as encouraged research in our field by awarding the $4500 Early Career Award to Richard Bazinet. In addition to all this, the ISSFAL 2008 organisers will have done their bit, by encouraging 63 New Investigators with free registrations and help with accommodation costs, plus the giving away of nine $500 laptops to those NI’s judged to have given the best presentations. But no doubt more on this will appear in the report from the Congress which our Newsletter Editor Francesco will be writing for the next issue. From the point of view of the Society, things are going very well, as my report to the members at Kansas City will have revealed. We now have more than 550 members paid up for either 2007 or 2008, and have processed a record number of new members this year, more than 110 so far, and we have a record number of Corporate members, 21 at present. The new (November 2006) website is getting a lot of hits (more than 60,000 per year), and generally seems to be well received, and provides members, among other facilities, with the ability to check on their dues status, which the old one did not do. For those not present at Kansas City, the minutes from the Business meeting will eventually
appear in the member-only section of the website, so you can catch up with what was said there. The abstracts from the meeting will also in due course appear in the Archive section of the website, but it will no doubt take me several months to get this mammoth task completed. The next big issue facing the Society is the election of a Vice-President and President Elect to take over from Philip Calder when he is elevated to the role of President in March 2009. At that time our current President Michel Lagarde will stand down as President, and take over the role of Past-President from Norman Salem Jnr. Norman will finally bow out of the ISSFAL Executive after his 9 year stint; I am sure I will be echoing the words of President Michel in paying tribute to the dedicated work put in by Norman during his time on the Executive. We must therefore seek nominations for the role of Vice-President and President Elect for the election which will be carried out early in 2009. Please send in nominations to me at [email protected]. I plan to mail ballot forms out in January, along with dues reminders for those that are not already paid for 2009. I should point out that we have now already more than 20 members that have paid up for 2009, so I would encourage you all to become members of the ‘‘2009 paid-up club’’ as soon as you can; I realise how easy it is to put it off, and before you know it, you end up running into arrears, or even worse, having your access to the Society terminated! Another change facing the Society is that my own final term of office expires in 2010, and the search will soon be under way for my replacement. If anyone is interested, or knows someone that might be interested in applying, please e-mail me, and I will pass the details along to the search sub-committee. I trust your summer break will have been invigorating (if you had one!) and that you will be ready to tackle the challenges ahead with renewed vigour.
Ray Rice Secretary/Treasurer, ISSFAL