Differences in transcriptional responses to acute and chronic dietary interventions with fatty acids
Matualatupauw, Juri C. - \ 2017
Wageningen University. Promotor(en): A.H. Kersten, co-promotor(en): L.A. Afman; J. Bouwman. - Wageningen : Wageningen University - ISBN 9789463432078 - 172
fatty acids - gene expression - genotyping - phenotypes - nutritional intervention - transcriptomics - fish oils - apolipoprotein e - adipose tissue - microarrays - polymerase chain reaction - vetzuren - genexpressie - genotyping - fenotypen - maatregel op voedingsgebied - transcriptomica - visoliën - apolipoproteïne e - vetweefsel - microarrays - polymerase-kettingreactie
Various types of dietary fatty acids have different effects on human health. The aim of this thesis was to increase our understanding of the molecular mechanisms underlying the effects of dietary fatty acids. To do this, we examined changes in whole genome gene expression profiles upon both acute as well as longer term dietary fatty acid interventions. Furthermore, from previous research, it is clear that large inter-individual differences in the response to dietary fatty acids exist. We used whole genome gene expression analyses to increase our understanding of the mechanisms underlying some of these inter-individual differences.
Many modifiable and non-modifiable factors can be the cause of these inter-individual differences. In chapter 2, we reviewed all studies that examined differences in the transcriptional response to dietary interventions based on the presence of one of these factors. These include gender, age, BMI, body composition, blood lipid levels and gut microbial composition. We conclude that transcriptome analyses are well-suited for studying the underlying mechanisms behind these differences in the response to diet. Nevertheless, the number of studies that use this approach remains limited.
Another factor that may modify the response to a dietary intervention is genetics, e.g. the apolipoprotein E4 (APOE4) variant. People who carry the APOE4 allele have an increased risk of cardiovascular disease. Fish-oil supplementation may help in the prevention of cardiovascular disease, though inter-individual differences in the response to n-3 polyunsaturated fatty acids on gene expression profiles have been observed. In chapter 3, we aimed to assess the impact of APOE4 on peripheral blood mononuclear cell (PBMC) whole genome gene expression at baseline and following a 6-month fish-oil intervention. We observed increased gene expression of IFN signaling and cholesterol biosynthesis pathways in APOE4 carriers, which might explain part of the association between APOE4 and CVD. Furthermore, fish-oil supplementation may be beneficial by decreasing interferon signalling-related gene expression in APOE4 carriers.
Another long-term dietary intervention with fatty acids was studied in chapter 4. We examined the effect of a 12-week high medium-chain saturated fatty acid diet on subcutaneous adipose tissue gene expression profiles. We observed increased expression of genes involved in oxidative energy metabolism and decreased inflammation-related gene expression due to the high medium-chain saturated fatty acid intake. Considering the role of the adipose tissue in sustaining the low-grade inflammation that is associated with obesity, these findings may be indicative of a more anti-inflammatory phenotype of the adipose tissue. We concluded that medium-chain saturated fatty acids may potentially have beneficial effects on adipose tissue functioning.
Besides studying the effects of long-term interventions with fatty acids on whole genome gene expression, we also examined the effects of acute high-fat challenges. In chapter 5, we determined the additional value of determining whole genome gene expression changes in response to a high-fat challenge compared to assessment at fasting only. In addition, we aimed to identify whether a 4 week high-fat high-calorie diet can induce a shift in gene expression profiles in healthy subjects towards a metabolic syndrome-like gene expression profile. We found that fasting whole blood whole genome gene expression profiles are highly responsive to a 4-week high-fat high-calorie diet, with changes in in the direction of a metabolic syndrome-like gene expression profile. High-fat challenge responses in healthy subjects show only minimal changes in gene expression upon the dietary intervention and a marginal shift in the direction of the metabolic syndrome. We concluded that fasting gene expression profiles are more responsive compared to high-fat challenge responses to a 4-week high-fat high-calorie diet.
Besides chapter 5, several other studies have also examined changes in whole genome gene expression in blood cells induced by high-fat challenges. In chapter 6, we combined microarray data from four high-fat challenge studies varying in study population, challenge composition and research laboratory. By performing this meta-analysis, we showed a general PBMC whole genome gene expression response to a high-fat challenge. We concluded that a meta-analysis provides added value for the discovery of consistently differentially expressed genes and pathways compared to selecting only those genes and pathways that are identified in all separate studies.
In conclusion, in this thesis we showed differences in the whole genome gene expression response to fish-oil supplementation in PBMCs of APOE4 carriers vs non-carriers. Furthermore, the effects on whole genome gene expression of the two long-term dietary interventions, i.e. the fish-oil supplementation in PBMCs of APOE4 carriers and the high medium-chain saturated fatty acid diet in adipose tissue, may be beneficial by downregulation of gene expression related to inflammation. We also showed that whole genome gene expression responses to high-fat challenges are affected by a 4-week high-fat high-calorie diet, though changes in fasting gene expression profiles are much more pronounced. Finally, we showed the value of meta-analysis of microarray data in high-fat challenge studies for identifying the general response to a high-fat challenge.
n-3 Fatty acid derived endocannabinoids: a new link between fish oil and inflammation
Balvers, M.G.J. - \ 2012
Wageningen University. Promotor(en): Renger Witkamp, co-promotor(en): K.C.M. Verhoeckx. - S.l. : s.n. - ISBN 9789461731159 - 206
omega-3 vetzuren - meervoudig onverzadigde vetzuren - visoliën - cannabinoïden - ontsteking - anti-inflammatoire eigenschappen - ontstekingsremmers - omega-3 fatty acids - polyenoic fatty acids - fish oils - cannabinoids - inflammation - antiinflammatory properties - antiinflammatory agents
Inflammatory processes are critical components of many illnesses, and dietary n-3 fatty acids have been shown to contribute to a reduction of the inflammatory status, both in in vivo and in vitro studies. The mechanisms underlying the modulation of inflammation are not completely understood, but it is clear that dietary n-3 fatty acids alter the eicosanoid metabolome profile, resulting in increased levels of n-3 fatty acid eicosanoids, whereas eicosanoids from other fatty acids are decreased. Until now, the anti-inflammatory properties of n-3 fatty acids had not been linked to an interaction with endocannabinoids/N-acyl ethanolamides (NAEs) levels before. This thesis describes a series of studies on the link between dietary fatty acids, endocannabinoids/NAEs, and inflammation.
Previous research indicated that dietary fatty acids alter the profile of endocannabinoids/NAEs rather than just affecting single compounds such as arachidonoyl ethanolamide (AEA) and 2-arachidonoyl glycerol (2-AG) as suggested before, and therefore a method based on liquid chromatography coupled to mass spectrometry (LC-MS/MS) to quantify a broad range of endocannabinoids/NAEs was developed. This method was used to demonstrate that n-3 fatty acids are converted to their endocannabinoid derivates by adipocytes in vitro. These n-3 derived NAEs, docosahexaenoyl ethanolamide (DHEA) and eicosapentaenoyl ethanolamide (EPEA), were shown to have anti-inflammatory properties in lipopolysaccharide (LPS)-stimulated adipocytes by reducing interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1) excretion. Further studies showed that serum free fatty acid levels and plasma NAE levels are correlated under both fasting and post-prandial conditions in women, and demonstrated that plasma AEA and oleoyl ethanolamide (OEA) correlated with body mass index (BMI).
Considering the complexity of endocannabinoid and eicosanoid metabolism, it is likely that their concentrations are dynamic over time and tissue-specific during inflammation. So far, most studies had focused on limited numbers of endocannabinoids and eicosanoids in restricted numbers of tissues or plasma, and the effect of inflammation on DHEA and EPEA levels had not been studied before. Therefore, an animal study was conducted which investigated in detail the time-dependent effects of i.p. LPS on the levels of lipid derived mediators (endocannabinoids/NAEs and eicosanoids) in plasma, liver, ileum and adipose tissue in mice fed with a diet rich in fish oil. The results demonstrated that both DHEA and EPEA levels were increased after LPS treatment, but also time- and tissue dependent effects were observed. Based on these data, another study was performed which investigated the combined effect of different fish oil diets and inflammation on the profiles of endocannabinoids and eicosanoids using the same multi-compartment targeted lipidomics approach. The data indicated that that dietary n-3 fatty acids and inflammation alter both the endocannabinoid and eicosanoid metabolomes towards higher levels of n-3 derived metabolites at the expense of metabolites derived from other fatty acids. Multivariate data analysis revealed that under normal conditions the diet groups were primarily separated based on decreased levels of other than n-3 derived metabolites. However, during inflammation, the separation was primarily explained by increases in n-3 derived compounds. Finally, additional analyses demonstrated that plasma and erythrocytes contain significant levels of esterified NAEs. The esterified levels were approximately 20-60 fold higher than the free NAE levels, and their profiles resembles the free NAE profiles.
In conclusion, (dietary) n-3 fatty acids increased the levels of DHEA and EPEA, and these metabolites displayed anti-inflammatory properties. Although the n-3 fatty acids are likely to be converted to a variety of other metabolites, the work in this thesis suggests that ‘fish oil-derived’ endocannabinoids are a new link between fish oil and its anti-inflammatory properties. Further research is needed to relate nutrition-based modulation of endocannabinoid profiles to more specific effects on health and disease.
Fish fatty acids and mental health in older people
Rest, O. van de - \ 2009
Wageningen University. Promotor(en): Lisette de Groot; Frans Kok, co-promotor(en): Marianne Geleijnse. - [S.l. : S.n. - ISBN 9789085854715 - 200
geestelijke gezondheid - mentale vaardigheid - depressie - visoliën - meervoudig onverzadigde vetzuren - ouderen - verouderen - omega-3 vetzuren - mental health - mental ability - depression - fish oils - polyenoic fatty acids - elderly - aging - omega-3 fatty acids
It has been suggested that the intake of fish and marine n-3 polyunsaturated fatty acids could protect against age-related cognitive decline and impaired mental well-being. However, results from observational studies are inconclusive and data from randomized controlled trials in older people without clinical dementia or depression are scarce. The objective of this thesis was to investigate the effect of daily supplementation with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on cognitive performance and mental well-being in an older non-clinical population. We also examined the effect of fish oil on gene expression profiles in white blood cells to identify early changes in pathways possibly related to mental health. Furthermore, we assessed the association of fish and EPA+DHA intake with mental health in different aging populations.
The effect of low and high doses of EPA+DHA (400 and 1,800 mg per day, respectively) on cognitive performance, several measures of mental well-being, and gene expression was examined in a 26-week randomized, double-blind, placebo-controlled trial. This study was conducted in 302 individuals aged 65 years or older with no clinical diagnosis of dementia or depression. Furthermore, the cross-sectional association between fatty fish and EPA+DHA intake with cognitive performance and the association with cognitive change during 6 years of follow-up was assessed in 1,025 aging US men who participated in the Veterans Affairs Normative Aging Study (NAS). In addition, the associations of EPA+DHA and fish intake with depressive symptoms and dispositional optimism were assessed in 644 free-living Dutch subjects with a history of myocardial infarction.
Daily intake of low or high doses of EPA+DHA did not affect cognitive performance, mental well-being, anxiety, or quality of life, after 13 or 26 weeks of intervention. However, treatment with EPA+DHA for 26 weeks altered gene expression in white blood cells to a more anti-inflammatory and more anti-atherogenic profile. In elderly US men we found no association of fatty fish or EPA+DHA intake with cognitive performance or 6-year cognitive change. Intake of EPA+DHA was positively associated with dispositional optimism in subjects with a history of myocardial infarction. There was also a tendency for less depressive symptoms with a higher EPA+DHA or fish intake, but this association was no longer statistically significant after controlling for confounders.
Supplemental intake of EPA+DHA is unlikely to have a short-term impact on cognitive performance or mental well-being of older people without a clinical diagnosis of dementia or depression. Whether long-term intake of EPA+DHA and fish could be beneficial to the maintenance of cognitive performance or mental well-being of older people in Western populations still needs to be established.
Very long-chain n-3 polyunsaturated fatty acids: a head start to win some years between the ears?
Dullemeijer, C. - \ 2009
Wageningen University. Promotor(en): Frans Kok; R.J. Brummer, co-promotor(en): I.A. Brouwer. - [S.l.] : S.n. - ISBN 9789085853770 - 136
vetzuren met een lange keten - hersenen - cognitieve ontwikkeling - mentale vaardigheid - visoliën - ouderen - vaatziekten - omega-3 vetzuren - kenvermogen - long chain fatty acids - brain - cognitive development - mental ability - fish oils - elderly - vascular diseases - omega-3 fatty acids - cognition
Very long-chain n-3 (or omega-3) polyunsaturated fatty acids have attracted considerable public interest during the past few years for their potential beneficial role in cognitive performance. The proposed benefits stretch from advantages in developing brains of infants and children to preventing cognitive decline at old age.
In this thesis, we first examined the role of very long-chain n-3 PUFA at the beginning of the lifespan. We investigated the effects of dietary very long-chain n-3 PUFA on the fatty acid composition of the several brain lobes in juvenile pigs, and showed that a diet enriched with fish oil resulted in higher proportions of DHA in the frontal, parietal and occipital brain lobes compared with the temporal brain lobe. These findings suggest a region-specific incorporation of DHA in the developing brain, which may guide future research into the mechanism by which very long-chain n-3 PUFA may in involved in brain development and function.
Subsequently, we investigated the role of very long-chain n-3 PUFA near the end of the lifespan. In a population of older adults, we investigated the association between very long-chain n-3 PUFA and cognitive decline over three years in multiple cognitive domains. We demonstrated that higher plasma proportions of very long-chain n-3 PUFA were associated with less decline in the cognitive domains sensorimotor speed and complex speed, but not in memory, information-processing speed and word fluency, compared with lower plasma proportions of very long-chain n-3 PUFA. These results suggest a beneficial role of very long-chain n-3 PUFA in the speed-related cognitive domains, which justifies future research in this area with sensitive cognitive outcome measurements that provide domain-specific information.
Finally, we touched upon the role of very long-chain n-3 PUFA in the macrovascular and the microvascular blood supply in the head region. We showed that plasma very long-chain n-3 PUFA were not associated with changes in carotid intima-media thickness and common carotid distension in a healthy older adult population. This may suggest that the role of very long-chain n-3 PUFA in a healthy population extends in particular to the smaller blood vessels. The role of very long-chain n-3 PUFA in the microcirculation of the brain could therefore be an interesting future direction of research. Although we did not directly investigate the role of very long-chain n-3 PUFA in the brain microcirculation, we did investigate whether plasma very long-chain n-3 PUFA were associated with age-related hearing loss over a period of three years in older adults. Since microvascular disease may decrease the blood supply to the highly vascularised cochlea, this may result in age-related hearing loss. We showed that higher plasma proportions of very long-chain n-3 PUFA were indeed associated with less age-related hearing loss compared with lower plasma proportions of very long-chain n-3 PUFA which implies that the hypothesis of improved microcirculation, if proven correct, may have far-reaching consequences.
In summary, this thesis showed that very long-chain n-3 PUFA have region-specific effects on the developing brain and that higher plasma proportions of very long-chain n-3 PUFA were associated with less decline in the speed-related cognitive domains and less age-related hearing loss. Further research is required to establish the role of very long-chain n-3 PUFA in the developing as well as the aging brain and to investigate the underlying mechanisms.
“Very long-chain n-3 polyunsaturated fatty acids: a head start to win some years between the ears?” PhD-thesis by Carla Dullemeijer, Top Institute Food and Nutrition and Division of Human Nutrition, Wageningen University, Wageningen, the Netherlands, May 15, 2009
Nutrigenomics in human peripheral blood mononuclear cells : the effects of fatty acids on gene expression profiles of human circulating cells as assessed in human intervention studies
Bouwens, M. - \ 2009
Wageningen University. Promotor(en): Michael Muller, co-promotor(en): Lydia Afman. - [S.l. : S.n. - ISBN 9789085853275 - 128
genotype-voeding interactie - vetzuren - bloedcellen - genexpressie - visoliën - maatregel op voedingsgebied - nutrigenomica - genotype nutrition interaction - fatty acids - blood cells - gene expression - fish oils - nutritional intervention - nutrigenomics
Research on the effects of nutrition on the function and health of organs in the human body, such as liver and intestine, is difficult, because for this research organ tissue is needed. Since nutrition research is usually performed in healthy volunteers, this tissue is difficult to obtain. However, to find out what happens on cellular level we do need human cells. Because blood cells are transported through the entire body and are relatively easy to obtain, these cells are ideal to study the effect of nutrition on cellular level. For this research we used the latest molecular genomics techniques to study the activity (on/off switching, increase/decrease) of all our genes at once. We found that consumption of different types of fat, both directly after consumption and after continued intake, changed the activity of specific groups of genes in these cells. With this research we have shown that the subtle effects of nutrition can be studied using nutrigenomics techniques in humans by using blood cells.
Production of high-quality fish oil from herring byproducts
Aidos, I.M.F. - \ 2002
Wageningen University. Promotor(en): R.M. Boom; A. van der Padt; J.B. Luten. - S.l. : S.n. - ISBN 9789058087287 - 203
visoliën - visverwerking - bijproducten - haringen - oxidatie - onverzadigde vetzuren - voedselkwaliteit - verwerkingskwaliteit - opslagkwaliteit - fish oils - fish processing - byproducts - herrings - oxidation - unsaturated fatty acids - food quality - processing quality - storage quality
In this work, the feasibility of producing high-quality fish oil from herring byproducts was evaluated in various ways. With this, a contribution has been made to a more efficient usage of natural resources while yielding a high-quality product. Crude oil extracted from herring byproducts is relatively rich in essentialw-3 PUFAs such as EPA and DHA, and is relatively stable during storage. The main conclusions of this study were: herring byproducts from the entire year are an adequate raw material for fish oil production; good quality fish oil can be produced from salted herring byproducts, and byproducts from different herring processing generate oils with different qualities. It is also shown that sorting of the byproducts does not result in oils of strongly different qualities, showing that this step is not required. However, it is concluded that from stored byproducts oil with higher levels of PUFAs content could be obtained. The best quality oil was achieved while processing at the highest throughput of the pump and at intermediate decanter speed. It has been observed that the best temperature to keep the oil is 0°C. The extracted crude herring oil presented relatively low levels of contaminants, PCBs and dioxins. Finally, the crude herring oil was refined and compared with commercially available menhaden oil. Similar properties such as oxidative stability and off-taste development were found. The currently obtained knowledge of fish oil extracted from herring byproducts is the first essential step towards the valorization of byproducts from different fatty fish species into production of fish oil, thereby contributing to a better utilization of the marine resources that are available.
|Anaerobe zuivering van zuur water op semi-technische schaal.
Rinzema, A. ; Schulz, C.E. - \ 1987
Wageningen : Landbouwuniversiteit - 71
anaërobe behandeling - visoliën - technologie - afvalwaterbehandeling - waterzuivering - anaerobic treatment - fish oils - technology - waste water treatment - water treatment
Determination of selected chlorobiphenyl congeners in fish oil with capillary gaschromatography (BCR interlaboratory study 4/1985)
Tuinstra, L.G.M.Th. ; Roos, A.H. - \ 1985
Wageningen : RIKILT (Report / RIKILT 85.76) - 9
visoliën - voedingsmiddelen - polychloorbifenylen - gaschromatografie - kwaliteitscontroles - fish oils - foods - polychlorinated biphenyls - gas chromatography - quality controls