Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

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The perceived impact of the National Health Service on personalised nutrition service delivery among the UK public
Fallaize, R. ; Macready, A.L. ; Butler, L.T. ; Ellis, J.A. ; Berezowska, A. ; Fischer, A.R.H. ; Walsh, M.C. ; Gallagher, C. ; Stewart-Knox, B.J. ; Kuznesof, S. ; Frewer, L.J. ; Gibney, M.J. ; Lovegrove, J.A. - \ 2015
The British journal of nutrition 113 (2015)8. - ISSN 0007-1145 - p. 1271 - 1279.
nutrigenomics - communication - disease - information - consumer - medicine - intervention - acceptance - knowledge - attitudes
Personalised nutrition (PN) has the potential to reduce disease risk and optimise health and performance. Although previous research has shown good acceptance of the concept of PN in the UK, preferences regarding the delivery of a PN service (e.g. online v. face-to-face) are not fully understood. It is anticipated that the presence of a free at point of delivery healthcare system, the National Health Service (NHS), in the UK may have an impact on end-user preferences for deliverances. To determine this, supplementary analysis of qualitative data obtained from focus group discussions on PN service delivery, collected as part of the Food4Me project in the UK and Ireland, was undertaken. Irish data provided comparative analysis of a healthcare system that is not provided free of charge at the point of delivery to the entire population. Analyses were conducted using the ‘framework approach’ described by Rabiee (Focus-group interview and data analysis. Proc Nutr Soc 63, 655-660). There was a preference for services to be led by the government and delivered face-to-face, which was perceived to increase trust and transparency, and add value. Both countries associated paying for nutritional advice with increased commitment and motivation to follow guidelines. Contrary to Ireland, however, and despite the perceived benefit of paying, UK discussants still expected PN services to be delivered free of charge by the NHS. Consideration of this unique challenge of free healthcare that is embedded in the NHS culture will be crucial when introducing PN to the UK.
Understanding consumer evaluations of personalised nutrition services in terms of the privacy calculus: a qualitative study
Berezowska, A. ; Fischer, A.R.H. ; Ronteltap, A. ; Kuznesof, S. ; Macready, A. ; Fallaize, R. ; Trijp, J.C.M. van - \ 2014
Public Health Genomics 17 (2014)3. - ISSN 1662-4246 - p. 127 - 140.
electronic commerce - nutrigenomics - information - nutrigenetics - model - trust - risk - perspectives - internet - antecedents
Background: Personalised nutrition (PN) may provide major health benefits to consumers. A potential barrier to the uptake of PN is consumers' reluctance to disclose sensitive information upon which PN is based. This study adopts the privacy calculus to explore how PN service attributes contribute to consumers' privacy risk and personalisation benefit perceptions. Methods: Sixteen focus groups (n = 124) were held in 8 EU countries and discussed 9 PN services that differed in terms of personal information, communication channel, service provider, advice justification, scope, frequency, and customer lock-in. Transcripts were content analysed. Results: The personal information that underpinned PN contributed to both privacy risk perception and personalisation benefit perception. Disclosing information face-to-face mitigated the perception of privacy risk and amplified the perception of personalisation benefit. PN provided by a qualified expert and justified by scientific evidence increased participants' value perception. Enhancing convenience, offering regular face-to face support, and employing customer lock-in strategies were perceived as beneficial. Conclusion: This study suggests that to encourage consumer adoption, PN has to account for face-to-face communication, expert advice providers, support, a lifestyle-change focus, and customised offers. The results provide an initial insight into service attributes that influence consumer adoption of PN.
Considering the path of nutrigenomics: a pragmatic ethical approach
Komduur, R.H. - \ 2013
Wageningen University. Promotor(en): Michiel Korthals, co-promotor(en): Hedwig te Molder. - S.l. : s.n. - ISBN 9789461735195 - 200
nutrigenomica - ethiek - voeding en gezondheid - voeding - voedsel - gezondheid - onderzoek - gezondheidsgedrag - levensstijl - genen - consumentengedrag - nutrigenomics - ethics - nutrition and health - nutrition - food - health - research - health behaviour - lifestyle - genes - consumer behaviour
Nutrigenomics research promises a future in which health risks of different diets can be exactly calculated on a personal basis. This seems great, but we need to consider how this will change our ideas about eating and health, and reflect on the ethical consequences of such a change. Therefore normative assumptions are compared within nutrigenomics research with norms about food, genes and health in everyday life.
Factors influencing European consumer uptake of personalised nutrition. Results of a qualitative analysis
Stewart-Knox, B. ; Kuznesof, S. ; Robinson, J. ; Rankin, A. ; Orr, K. ; Duffy, M. ; Poinhos, R. ; Almeida, M.D.V. de; Macready, A. ; Gallagher, C. ; Berezowska, A. ; Fischer, A.R.H. ; Navas-Carretero, S. ; Riemer, M. ; Traczyk, I. ; Gjelstad, I.M.F. ; Mavrogianni, C. ; Frewer, L.J. - \ 2013
Appetite 66 (2013). - ISSN 0195-6663 - p. 67 - 74.
genetic research - food - attitudes - nutrigenomics - acceptance - risks - perceptions - benefits - hazards - focus
The aim of this research was to explore consumer perceptions of personalised nutrition and to compare these across three different levels of “medicalization”: lifestyle assessment (no blood sampling); phenotypic assessment (blood sampling); genomic assessment (blood and buccal sampling). The protocol was developed from two pilot focus groups conducted in the UK. Two focus groups (one comprising only “older” individuals between 30 and 60 years old, the other of adults 18–65 yrs of age) were run in the UK, Spain, the Netherlands, Poland, Portugal, Ireland, Greece and Germany (N = 16). The analysis (guided using grounded theory) suggested that personalised nutrition was perceived in terms of benefit to health and fitness and that convenience was an important driver of uptake. Negative attitudes were associated with internet delivery but not with personalised nutrition per se. Barriers to uptake were linked to broader technological issues associated with data protection, trust in regulator and service providers. Services that required a fee were expected to be of better quality and more secure. An efficacious, transparent and trustworthy regulatory framework for personalised nutrition is required to alleviate consumer concern. In addition, developing trust in service providers is important if such services to be successful
Consumers on the Internet: ethical and legal aspects of commercialization of personalized nutrition
Ahlgren, J. ; Nordgren, A. ; Perrudin, M. ; Ronteltap, A. ; Savigny, J. ; Trijp, J.C.M. van; Nordström, K. ; Görman, U. - \ 2013
Genes & Nutrition 8 (2013)4. - ISSN 1555-8932 - p. 349 - 355.
nutrigenomics - acceptance
Consumers often have a positive attitude to the option of receiving personalized nutrition advice based upon genetic testing, since the prospect of enhancing or maintaining one’s health can be perceived as empowering. Current direct-to-consumer services over the Internet, however, suffer from a questionable level of truthfulness and consumer protection, in addition to an imbalance between far-reaching promises and contrasting disclaimers. Psychological and behavioral studies indicate that consumer acceptance of a new technology is primarily explained by the end user’s rational and emotional interpretation as well as moral beliefs. Results from such studies indicate that personalized nutrition must create true value for the consumer. Also, the freedom to choose is crucial for consumer acceptance. From an ethical point of view, consumer protection is crucial, and caution must be exercised when putting nutrigenomic-based tests and advice services on the market. Current Internet offerings appear to reveal a need to further guaranty legal certainty by ensuring privacy, consumer protection and safety. Personalized nutrition services are on the borderline between nutrition and medicine. Current regulation of this area is incomplete and undergoing development. This situation entails the necessity for carefully assessing and developing existing rules that safeguard fundamental rights and data protection while taking into account the sensitivity of data, the risks posed by each step in their processing, and sufficient guarantees for consumers against potential misuse
Consumption of a high monounsaturated fat diet reduces oxidative phosphorylation gene expression in peripheral blood mononuclear cells of abdominally overweight men and women
Dijk, S.J. van; Feskens, E.J.M. ; Bos, M.B. ; Groot, C.P.G.M. de; Vries, J.H.M. de; Muller, M.R. ; Afman, L.A. - \ 2012
The Journal of Nutrition 142 (2012)7. - ISSN 0022-3166 - p. 1219 - 1225.
virgin olive oil - mediterranean diet - metabolic syndrome - skeletal-muscle - growth-factor - health - nutrigenomics - stress - humans - complications
The Mediterranean (MED) diet is often considered health-promoting due to its high content of MUFA and polyphenols. These bioactive compounds can affect gene expression and accordingly may regulate pathways and proteins related to cardiovascular disease prevention. This study aimed to identify the effects of a MED-type diet, and the replacement of SFA with MUFA in a Western-type diet, on peripheral blood mononuclear cell (PBMC) gene expression and plasma proteins. Abdominally overweight men and women (waist: women =80 cm, men =94 cm) were allocated to an 8-wk, completely controlled SFA diet (19% daily energy as SFA), a MUFA diet (20% daily energy MUFA), or a MED diet (21% daily energy MUFA). Concentrations of 124 plasma proteins and PBMC whole-genome transcriptional profiles were assessed. Consumption of the MUFA and MED diets, compared with the SFA diet, decreased the expression of oxidative phosphorylation (OXPHOS) genes, plasma connective tissue growth factor, and apoB concentrations. Compared with the MED and SFA diets, the MUFA diet changed the expression of genes involved in B-cell receptor signaling and endocytosis signaling. Participants who consumed the MED diet had lower concentrations of proinflammatory proteins at 8 wk compared with baseline. We hypothesize that replacement of SFA with MUFA may improve health, thereby reducing metabolic stress and OXPHOS activity in PBMC. The MED diet may have additional antiatherogenic effects by lowering proinflammatory plasma proteins
Mapping the diverse functions of dietary fatty acids via target gene regulation
Georgiadi, A. - \ 2012
Wageningen University. Promotor(en): Michael Muller; Sander Kersten. - S.l. : s.n. - ISBN 9789461732804 - 200
vetzuren - dieet - genregulatie - nutrigenomica - fatty acids - diet - gene regulation - nutrigenomics

Dietary fat is a strong predictor of chronic diseases, such as cardiovascular diseases, obesity, diabetes, dyslipidemia and metabolic syndrome. A great number of epidemiological and observational studies clearly show that in addition to the amount of fat consumed in a diet, fat composition is an equally important factor in the development of chronic diseases. Evidence abounds indicating that adherence to a diet with high content of polyunsaturated (PUFAs) and monounsaturated fatty acids (MUFAs) such as the Mediterranean diet has substantial health benefits, while diets with high content of saturated fatty acids (SFAs) such as the Western type diet increase the risk for the development of several chronic diseases.

Nutritional genomics or nutrigenomics investigates the interaction between nutrients and genes at the molecular level, by using genomic tools. Within the field of nutrigenomics, dietary fatty acids and their metabolites are seen as signaling molecules that target specific cellular response systems. Dietary fatty acids have been reported to bind physically to PPARs, a family of ligand activated transcription factors, that play a major role in metabolic homeostasis. Three PPAR isotypes have been identified, PPARα, PPARβ/δ and PPARγ. Their expression and target genes vary among different tissues and cell types.

After a meal triglycerides are packed into chylomicrons in the small intestine and via the lymph system, they reach the blood and the peripheral tissues. Triglyceride chylomicrons deliver free fatty acids to the organs after being lipolylised by lipoprotein lipase (LPL), which is anchored to the capillary endothelium. Among different organs, heart and liver show the highest uptake of dietary triglycerides, postprandialy. However, opposite to the liver, heart is a constant working muscle, which covers its demands on energy mainly by fatty acids, delivered to the heart via hydrolysis of circulating triglyceride-rich lipoproteins. Unbalanced fatty acid uptake and fatty acid oxidation is common in cardiac diseases, such as cardiac failure, myocardial ischemia and diabetes. Heart is characterized by decreased lipid storage capacity, therefore chronic elevated levels of lipids uptake and intracellular storage is considered harmful and may lead to lipotoxic cardiomyopathy.

Our first aim was to explore the whole genome effects of individual dietary fatty acids in the intact heart via transcriptional profiling. By conducting these experiments in wild-type and PPARα−/− mice, we aimed to determine the specific contribution of PPARα, which has been previously described as a master regulator of lipid homeostasis in the heart. We took advantage of a unique experimental model, where mice were given a single oral bolus of synthetic triglycerides composed of a single fatty acid. We sacrificed the mice 6hours after the oral gavage and we compared the effects of different fatty acids on gene expression by microarray analysis in the total heart. Many genes were regulated by one particular treatment only and among those most of them showed large functional divergence. Although, the majority of genes responding to fatty acid treatment were regulated in a PPARα-dependent manner, emphasizing the importance of PPARα in mediating transcriptional regulation by fatty acids in the heart, we observed a substantial number of genes regulated in a PPARα- independent manner. Finally, we observed that deletion and activation of PPARα had a major effect on expression of numerous genes involved in metabolism and immunity.

We identified response to oxidative stress as the top upregulated process activated by all administered fatty acids in the heart. High rates of mitochondria oxidation, due to increased supply of substrate after the oral gavage are coupled with enzymatic and non- enzymatic mechanisms aiming to counterbalance the production of highly reactive secondary products of the respiratory chain, the reactive oxygen species (ROS) in the heart. Under conditions such as chronic high fat diet or insulin resistance, increased lipid influx in combination with uncontrolled production of ROS and lipid intermediates may result in mitochondrial malfunctioning and lipid accumulation. Myocardial lipotoxicity refers to the accumulation of intramyocardial lipids and is associated with contractile dysfunction and even myocytes death. We found Angptl4 to be the top upregulated gene, in all groups that received the fatty acids oral gavage. Angptl4 has been described as a target gene of PPARs and an endogenous inhibitor of the triglyceride hydrolyzing enzyme lipoprotein lipase (LPL), which catalyzes uptake of circulating lipids into tissues. We were able to show that the strong upregulation of Angptl4 by dietary fatty acids is mediated by PPARβ/δ and is part of a feedback mechanism aimed at protecting the heart against lipid overload and consequently fatty acid–induced oxidative stress, one of the hallmarks of lipotoxic cardiomyopathy.

Angptl4 has been shown to have a potent inhibitory effect in LPL activity and subsequent reduction in uptake of lipids by several tissues and cell types, including macrophages. Furthermore, Angptl4 was shown to prevent the formation of foam cells in mesenteric lymph nodes upon high fat feeding. Accordingly, we hypothesized that Angptl4 may affect atherosclerosis development by reducing foam cell formation. Thus, our second aim was to investigate the role of Angptl4 on atherosclerosis development. We studied Angptl4 expression in atherosclerotic lesions and macrophages and determined the effect of Angptl4 transgenic overexpression in atherosclerosis prone ApoE3Leiden (E3L) mice fed a Western diet containing 0.4% cholesterol. We observed a decrease in atherosclerosis in Angptl4 overexpressing mice on an ApoE3L background. This effect was independent of the plasma cholesterol and triglyceride levels. Importantly, Angptl4Tg.E3L exhibited a less pro- inflammatory phenotype with decreased accumulation of monocytes/macrophages in the atherosclerotic plaque, suggesting an anti-inflammatory role of Angptl4 in atherosclerosis development.

Finally, we set out to identify transcriptional targets of fatty acids in macrophages, as part of a general goal to elucidate mechanisms through which fatty acids exhibit a direct role in modulating inflammatory processes in macrophages. We identified Hig-2 to be strongly upregulated by all treatments. We found expression of Hig-2 to be the highest in peritoneal macrophages and white adipose tissue. Chronic high fat feeding increased Hig-2 expression levels in adipose tissue but not in liver. Immunohistochemistry indicated colocalization of Hig-2 with Cd68 in infiltrating macrophages as part of crown-like structures. Based on these findings we propose that Hig-2 has a specific role in macrophages and may function as an interesting target in the study of obese adipose tissue.

In conclusion, this thesis contributes new information on gene regulation by dietary PUFA in the mammalian heart and provides mechanistic insight on their previous reported beneficial effects. Furthermore, we reveal a novel protective role of Angptl4 in atherosclerosis development. We propose that this effect is mediated by a mechanism, which is independent of inhibition of LPL-mediated systemic lipid clearance and it is probably related to the effect of Angptl4 on macrophage oxLDL uptake and chemotaxis. Finally, in the present thesis we start up an effort to identify fatty acid target genes in macrophages, which open new future research paths.

Dietary saturated fat/cholesterol, but not unsaturated fat or starch, induces C-reactive protein associated early atherosclerosis and ectopic fat deposition in diabetic pigs
Koopmans, S.J. ; Dekker, R.A. ; Ackermans, M.T. ; Sauerwein, H.P. ; Serlie, M.J. ; Beusekom, H.M.M. ; Heuvel, M. van den; Giessen, W.J. - \ 2011
Cardiovascular Diabetology 10 (2011). - ISSN 1475-2840 - 11 p.
cardiovascular-disease - insulin-resistance - coronary-arteries - carbohydrate - inflammation - interleukin-6 - nutrigenomics - hyperglycemia - proliferator - nutrition
Background Diabetes is thought to accelerate cardiovascular disease depending on the type of diet. This study in diabetic subjects was performed to investigate the metabolic, inflammatory and cardiovascular effects of nutritional components typically present in a Western, Mediterranean or high glycaemic diet. Methods Streptozotocin-diabetic pigs (~45 kg) were fed for 10 weeks supplemental (40% of dietary energy) saturated fat/cholesterol (SFC), unsaturated fat (UF) or starch (S) in an eucaloric dietary intervention study. Results Fasting plasma total, LDL and HDL cholesterol concentrations were 3-5 fold higher (p <0.01) in SFC compared to UF and S pigs. Fasting plasma NEFA concentrations (mmol/L) were highest (p <0.05) in SFC (1.09 ± 0.17), intermediate in UF (0.80 ± 0.14) and lowest in S pigs (0.58 ± 0.14) whereas plasma glucose (~13 mmol/L), triglyceride (~0.5 mmol/L) and insulin (~24 pmol/L) concentrations were comparable among SFC, UF and S pigs. The postprandial response area under the curves (AUC, 0-4 h) for glucose but not for insulin and triglyceride responses were intermediate in SFC (617 ± 144) and lowest (p <0.05) in UF (378 ± 157) compared to S pigs (925 ± 139). Fasting hepatic glucose production, hepatic and peripheral insulin sensitivity and blood pressure were not different among pigs. C-reactive protein (CRP) concentrations (mg/L) were highest (p <0.05) in SFC (25 ± 4), intermediate in S (21 ± 3) and lowest in UF pigs (14 ± 2). Liver weights, liver and muscle triglyceride concentrations, and the surface area of aorta fatty streaks were highest (p <0.01) in SFC pigs. A positive correlation between postprandial plasma CRP and aorta fatty streaks was observed in SFC pigs (R2 = 0.95). Retroperitoneal fat depot weight (g) was intermediate in SFC (260 ± 72), lowest in S (135 ± 51) and highest (p <0.05) in UF (571 ± 95) pigs. Conclusion Dietary saturated fat/cholesterol induces inflammation, atherosclerosis and ectopic fat deposition whereas an equally high dietary unsaturated fat load does not induce these abnormalities and shows beneficial effects on postprandial glycaemia in diabetic pigs. Keywords: Diabetes; Insulin; Diet; Unsaturated fat; Saturated fat; Cholesterol; Inflammation; C-reactive protein; Atherosclerosis; Pigs
Dietary fat and the prevention of type 2 diabetes: impact on inflammation and underlying mechanisms
Dijk, S.J. van - \ 2011
Wageningen University. Promotor(en): Michael Muller, co-promotor(en): Edith Feskens; Lydia Afman. - [S.l.] : S.n. - ISBN 9789461730466 - 143
diabetes type 2 - voedingsvet - ziektepreventie - genexpressieprofilering - biomarkers - ontsteking - nutrigenomica - type 2 diabetes - dietary fat - disease prevention - gene expression profiling - inflammation - nutrigenomics

The incidence of metabolic syndrome, which is a risk factor for cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) is increasing rapidly. Changes in dietary fat composition from saturated fat (SFA) to monounsaturated fat (MUFA) from olive oil, which is highly consumed in a Mediterranean diet, might improve risk factors for CVD and T2DM. However, the underlying molecular mechanisms for these beneficial health effects are not completely known. Moreover, more knowledge is needed about health status and biomarkers that allow early detection of onset of diseases such as metabolic syndrome, CVD and T2DM.

The aim of this thesis was twofold; first, to investigate the acute and longer-term effects of intake of different types of dietary fat. Second, to examine whether a more comprehensive phenotyping of health status can be achieved by application of nutrigenomics tools and challenges tests.

A controlled dietary intervention study was performed in healthy abdominally overweight subjects to investigate the effects of 8-weeks consumption of diets high in SFA or MUFA on insulin sensitivity, serum lipids and adipose tissue whole genome gene expression. Moreover, the effects of replacement of SFA by MUFA, as part of a western-type diet and as part of a Mediterranean diet, on peripheral blood mononuclear cell (PBMC) whole genome gene expression and plasma protein levels were investigated.

Plasma protein profiles of the subjects before the intervention were used to define proteins and protein clusters that were associated with BMI and insulin concentrations. Similar analyses were performed in a second overweight population to verify the findings.

In two other studies, the response capacity of subjects with different metabolic risk phenotypes to a high-fat challenge varying in fat type and to an extreme caloric restriction challenge were determined.

Results from our first study showed that consumption of a SFA-rich diet increased expression of inflammation-related genes in adipose tissue whereas consumption of a MUFA-rich diet led to a more anti-inflammatory gene expression profile, without changes in insulin sensitivity or increases in body weight. Moreover, high MUFA intake from olive oil, both in a western-type diet and in a Mediterranean-type diet, lowered expression of genes involved in oxidative phosphorylation in PBMCs and lowered serum LDL and plasma ApoB, Connective Tissue Growth Factor and myoglobin concentrations.

In plasma of the healthy participants clusters of proteinsassociated with BMI or insulin could be identified. These clusters included previously reported biomarkers for disease and potential new biomarkers.

The high-fat challenge study showed that the plasma metabolic response and the PBMC gene expression response to high-fat challenges were affected by the presence of obesity and/or diabetes. Comparison of responses to high SFA, MUFA and n-3 PUFA loads showed that a highMUFA load induced the most pronounced response.

The caloric restriction study revealed that PBMC gene expression profiles were different between metabolic syndrome subjects and healthy subjects, mainly for genes involved in pathways related to mitochondrial energy metabolism. Moreover, we observed that the caloric restriction challenge magnified differences in PBMC gene expression profiles between the subject groups.

In conclusion, this thesis showed that 8-weeks consumption of a SFA-rich diet resulted in a pro-inflammatory gene expression profile in adipose tissue whereas consumption of a MUFA-rich diet caused a more anti-inflammatory profile, in addition to reductions in LDL cholesterol, some plasma proteins and expression of oxidative phosphorylation genes in PBMCs. Since the effects of the diets on inflammation were still local and not accompanied by systemic changes in inflammatory status or insulin sensitivity we hypothesize that adipose tissue could be an early response organ for dietary fat-induced changes. The changes in pro-inflammatory gene expression might be one of the first hallmarks in the development of adipose tissue inflammation and insulin resistance which on the longer term may lead to inflammation-related diseases such as metabolic syndrome.

Our studies showed the potential of whole genome expression profiling, plasma profiling and the use of challenges tests to detect subtle diet effects and small differences in health status. Using these tools in future studies will result in more knowledge about health status and about mechanisms behind dietary effects. Eventually this might lead to earlier detection of small deviations from a healthy phenotype and to evidence-based dietary advice to improve health and to prevent disease.

Genetics and genomics of cholesterol and polyunsaturated fatty acid metabolism in relation to coronary heart disease risk
Lu Yingchang (Kevin), Y. - \ 2011
Wageningen University. Promotor(en): Edith Feskens; Michael Muller, co-promotor(en): J.M.A. Boer. - [S.l.] : S.n. - ISBN 9789461730350 - 216
lipidenmetabolisme - cholesterol - meervoudig onverzadigde vetzuren - hartziekten - risicoschatting - genetische factoren - nutrigenomica - lipid metabolism - polyenoic fatty acids - heart diseases - risk assessment - genetic factors - nutrigenomics

Background

Coronary heart disease (CHD) continues to be a leading cause of morbidity and mortality among adults worldwide. Deregulated lipid metabolism (dyslipidemia) that manifests as hypercholesterolemia, hypertriglyceridemia, low high-density-lipoprotein (HDL) cholesterol levels or a combination of those, is an established risk factor for CHD among other established risk factors. Linoleic acid (LA, C18:2n-6) and alpha-linolenic acid (ALA, C18:3n-3) are polyunsaturated fatty acids (PUFAs) that cannot be synthesized de novo by human or animal cells, and therefore must be obtained from the diet. From these two PUFAs, two series of long-chain PUFAs are formed; the omega-6 series that are synthesized from LA, and the omega-3 series that are from ALA. Formation of these long-chain PUFAs involves a series of alternate desaturation and elongation processes. These PUFAs, especially, omega-3 PUFAs, have long been observed to reduce CHD risk. In contrast to the consistently observed cardiovascular protective effects of omega-3 PUFAs, accumulating evidence suggests a potential pro-atherogenic effects of omega-6 PUFAs, which is now still under debate.

It has been estimated that genetic factors account for 26%-69% of inter-individual variation in CHD risk. These genetic factors are thought to influence CHD risk both directly and through effects on known CHD risk factors such as plasma lipid levels. The heritability of plasma lipid levels (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides (TG)) is estimated to be about 50% (ranging from 28%-78%). With the success of recent genome-wide association studies (GWAS), many genetic variants underlying intermediate risk factors of CHD (including plasma lipid levels) and CHD itself have been identified. Whether this new genetic information could be used to improve CHD risk prediction is still marginally explored, and for some variants, the underlying mechanisms for their mediated effects on CHD risk are still unknown. The aim of this research is to investigate common genetic determinants of plasma lipid levels (cholesterol and polyunsaturated fatty acid levels) using a pathway-driven approach, and to explore whether such common genetic variants could be used to improve CHD prediction using a population based genetic approach. An additional aim was to explore the underlying mechanisms of cardiovascular protective effects of PUFAs using a genomic approach.

Methods

In order to explore whether common genetic variants are involved in determining plasma cholesterol levels, we used data from 3575 men and women from the Doetinchem cohort, which was examined thrice over 11 years. They were genotyped on 384 single nucleotide polymorphisms (SNPs) across 251 genes in regulatory pathways that control fatty acid, glucose, cholesterol and bile salt homeostasis.

In order to explore whether common genetic variants could be used to predict future CHD risk,we used the data from CAREMA cohort that involved 15,236 middle-aged subjects and was followed up for a median of 12.1 years. 179 SNPs associated with CHD or its risk factors in GWAS published up to May 2, 2011 were genotyped in the 2221 subcohort members and 742 incident CHD cases. In addition, fatty acids from plasma cholesteryl esters were quantified in 1323 subcohort members and 537 CHD cases. They were used to explore whether δ-5 and δ-6 desaturase activities were associated with CHD risk.

In order to perform a comparative analysis of the effects of fenofibrate and fish oil at transcriptome and metabolome level, 34 mice were randomized by weight-matching into three groups (n = 10 in control group, and n = 12 in fenofibrate or fish oil intervention group), and fed a research diet supplemented with sunflower oil (containing 81.3% oleic acid, 7% energy intake) in control group, sunflower oil (7% energy intake) and fenofibrate (0.03% w/w) in fenofibrate group, and fish oil (Marinol C-38 fish oil: 23.1% EPA and 21.1% DHA, 7% energy intake) in fish oil group for 2 weeks. At the end of treatment, mice were fasted with drinking water available, and were subsequently sacrificed by cervical dislocation under isoflurane anesthesia. Blood was collected via orbital puncture. Livers were dissected, directly frozen in liquid nitrogen and stored at −80°C until further analysis. Microarray analysis was performed on individual mouse livers. The LC-MS method was used for measuring plasma lipids and non-esterified free fatty acids, and the GC-MS method was used for measuring a broad range of metabolites.

Results

In chapter 2, 3, and 4, common genetic variants in the genes along known cholesterol metabolic pathways, such as bile acid and bile metabolic pathways, the HDL cholesterol metabolic pathway, and the plasma total cholesterol metabolic pathway, are involved in determining plasma cholesterol levels. The modest effect associated with each individual variant, however, caused the amount of heritability explained by them in aggregate to be relatively small: 13 single nucleotide polymorphisms (SNPs) explained 4% of inter-individual variation in HDL cholesterol levels (Chapter 3), whereas 12 SNPs explained 6.9% of inter-individual variation in total cholesterol levels (Chapter 4).

In chapter 5, we found that genetic variants in the FADS1 gene potentially interact with dietary PUFA intake to affect plasma cholesterol levels. A high intake of omega-3 PUFAs was associated with increased plasma non-HDL cholesterol levels, consistent with increased plasma LDL cholesterol levels observed in fish oil intervention studies. Increased LDL cholesterol levels could be due to hepatic downregulation of the LDL receptor gene (LDLR) in subjects with high omega-3 PUFA intakes. This is further confirmed by the findings described in Chapter 6 that the hepatic LDLR gene was significantly downregulated in fish oil treated mice. This study also confirmed PUFAs to be weak PPAR ligands. The increased plasma HDL cholesterol levels in the subjects with high PUFA intakes in Chapter 5 could be due to PPARs-mediated genes that are directly involved in HDL lipoprotein metabolism. All these may explain the changes in blood cholesterol levels upon PUFA intake observed in human studies.

In Chapter 6, we found that not only downregulation in the hepatic lipogenic pathway but also upregulation in hepatic fatty acid oxidation pathways are involved in lowering plasma TG levels upon fish oil treatment. The striking parallel between fenofibrate and fish oil in hepatic downregulation of blood coagulation and fibrinolysis pathways suggest that hepatic activation of PPARα is potentially one of the mechanisms responsible for anticoagulation effects of fish oil treatment observed in humans.

In Chapter 7, with confirmed effects of rs174547 in FADS1 on PUFA levels and δ-5 desaturase activities and also protective effects of DHA on CHD, we observed a reduced CHD risk of increased δ-5 desaturase activity. Increased δ-5 desaturase activity could contribute to the intracellular increase of EPA and especially arachidonic acid (C20:4n-6) levels. Despite the potential pro-coagulant and pro-inflammatory effects of increased exposures of arachidonic acid and its derived eicosanoid metabolites, there is no evidence of increased CHD risk with increased habitual arachidonic acid intake so far. Some of the oxygenated metabolites of arachidonic acid were found to have anti-inflammatory and pro-resolving actions. High dietary n-6 PUFA intakes or high plasma n-6 PUFA levels are associated with increased blood HDL cholesterol levels and reduced TG (or VLDL particle) levels. All these point to a potential cardiovascular protective effect of n-6 PUFAs. The fact that increased EPA and/or DHA levels associated with increased δ-5 desaturase activity protect against CHD is consistent with the current established cardiovascular protective effect of increased n-3 PUFA exposure, especially EPA and DHA.

In Chapter 8, the current known common genetic variants associated with CHD risk factors (blood pressure, obesity, blood lipid levels, and type 2 diabetes) and CHD itself from published GWAS are examined to see whether they provide additional value in CHD risk prediction beyond established traditional CHD risk factors. We constructed several gene risk scores (GRS) for CHD that consisted of SNPs directly associated with CHD or intermediate CHD risk factors in GWAS, and tested their relationship to incident CHD and their potential to improve risk prediction. The weighted GRS based on 29 CHD SNPs predicted future CHD independently from established traditional risk factors. However, the GRS based on 153 SNPs associated with intermediate risk factors and the GRS based on the total 179 SNPs did not. None of them improved risk discrimination. Risk classification of CHD, measured by the net reclassification index, improved only when the GRS based on the 29 CHD SNPs was used. These results are generally consistent with the results from other recent studies that took a similar approach as ours. However, the final conclusions on GRS application could not be drawn at this early stage. With a great understanding of the genetic architecture of CHD in the future, more research should be done on this topic.

Conclusions

Our studies in this thesis demonstrated that common genetic variants along the known candidate cholesterol metabolic pathways are involved in determining the plasma cholesterol levels. PUFAs are not only weak PPARα ligands, but also inhibit SREBPs’ activities. All these could explain part of the cardiovascular protective effects (increased HDL cholesterol levels and reduced TG levels) of PUFAs, increased LDL cholesterol levels upon fish oil treatment in humans, and potentially reduced CHD risk of high δ-5 desaturase activities. At present, many questions remain about the feasibility of genetic risk prediction of CHD. Clinicians should continue to inquire about family history of CHD for risk prediction, because this represents a simple, cheap, and useful risk factor for CHD that likely represents the net integrated effects from hundreds of genetic risk variants.

Nutrigenomics: over eten, genen en gezondheid
Kersten, Sander - \ 2010
nutrigenomics - nutrition and health - health protection - genes - diet counseling
PPARa: master regulator of lipid metabolism im mouse and human : identification of hepatic PPARa target genes by expression profiling
Rakhshandehroo, M. - \ 2010
Wageningen University. Promotor(en): Michael Muller, co-promotor(en): Sander Kersten. - [S.l. : S.n. - ISBN 9789085857716 - 238
lipidenmetabolisme - transcriptiefactoren - genexpressie - muizen - mens - nutrigenomica - lipid metabolism - transcription factors - gene expression - mice - man - nutrigenomics
The peroxisome proliferator activated receptor alpha (PPARα) is a ligand activated tran- scription factor involved in the regulation of a variety of processes, ranging from inflam- mation and immunity to nutrient metabolism and energy homeostasis. PPARα serves as a molecular target for hypolipidemic fibrates drugs which bind the receptor with high affinity. Furthermore, PPARα binds and is activated by numerous fatty acids and fatty acid derived compounds. PPARα governs biological processes by altering the expression of large number of target genes. Although the role of PPARα as a gene regulator in liver has been well estab- lished, a comprehensive overview of its target genes has been missing so far. Additionally, it is not very clear whether PPARα has a similar role in mice and humans and to what extent target genes are shared between the two species. The aim of the research presented in this thesis was to identify PPARα-regulated genes in mouse and human liver and thereby further elucidate hepatic PPARα function. The applied nutrigenomics approaches are mainly expression microarrays combined with knockout mouse models and in vitro cell culture systems. By combining several independent nutrigenomics studies, we generated a comprehensive overview of PPARα-regulated genes in liver with the focus on lipid metabolism. We identi- fied a large number of PPARα target genes involved in different aspects of lipid metabolism. Furthermore, a major role of PPARα in lipogenesis was detected. Our data pointed to several novel putative PPARα target genes. Next, we compared PPARα-regulated genes in primary mouse and human hepatocytes treated with the PPARα agonist Wy14643 and generated an overview of overlapping and species specific PPARα target genes. A large number of genes were found to be regulated by PPARα activation in human primary hepatocytes, which iden- tified a major role for PPARα in human liver. Interestingly, we could characterize mannose binding lectin 2 (Mbl2) as a novel human specific PPARα target gene. Plasma Mbl2 levels were found to be changed in subjects receiving fenofibrate treatment or upon fasting. Regula- tion of Mbl2 by PPARα suggests that it may play a role in regulation of energy metabolism, although additional research is needed. We also compared the PPARα-induced transcriptome in HepG2 cells versus primary human hepatocytes to investigate the suitability of HepG2 cells in PPARα research. The results re- vealed that the HepG2 cell line poorly reflects the established PPARα target genes and func- tion, specifically with respect to lipid metabolism. Finally, we characterized the transcription factors Klf10 and Klf11 as novel PPARα target genes. Our preliminary findings using in vitro transfection assays and in vivo tail vein injection of plasmid DNA suggested a potential metabolic role of Klf10 and Klf11 in liver. In conclusion, this thesis has extended our understanding of PPARα-regulated genes and function in liver, and has specifically highlightened a major role of PPARα in human hepa- tocytes. This research has also given birth to a possible biomarker of hepatic PPARα activity which is of great interest for future studies. Considering the need for proper biomarkers in the field of nutrigenomics and beyond, the properties of Mbl2 as a biomarker should be further investigated. The identification of other novel putative PPARα target genes offers ample op- portunities for continued research.
Fish-oil supplementation induces antiinflammatory gene expression profiles in human blood mononuclear cells
Bouwens, M. ; Rest, O. van de; Dellschaft, N. ; Grootte Bromhaar, M.M. ; Groot, C.P.G.M. de; Geleijnse, J.M. ; Müller, M.R. ; Afman, L.A. - \ 2009
American Journal of Clinical Nutrition 90 (2009). - ISSN 0002-9165 - p. 415 - 424.
polyunsaturated fatty-acids - activated receptor-alpha - docosahexaenoic acid - cytokine production - murine macrophages - oxidative stress - controlled-trial - nitric-oxide - n-3 - nutrigenomics
Background: Polyunsaturated fatty acids can have beneficial effects on human immune cells, such as peripheral blood mononuclear cells (PBMCs). However, the mechanisms of action of polyunsaturated fatty acids on immune cells are still largely unknown. Objective: The objective was to examine the effects of supplementation with the polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on whole-genome PBMC gene expression profiles, in healthy Dutch elderly subjects participating in a double-blind trial, by using whole-genome transcriptomics analysis. Design: The subjects were randomly allocated to 1 of 3 groups: 1) consumption of 1.8 g EPA+DHA/d (n = 36), 2) consumption of 0.4 g EPA+DHA/d (n = 37), or 3) consumption of 4.0 g high–oleic acid sunflower oil (HOSF)/d (n = 38). All supplements were given in capsules. Before and after 26 wk of intervention, blood samples were collected. Microarray analysis was performed on PBMC RNA from 23 subjects who received 1.8 g EPA+DHA/d and 25 subjects who received HOSF capsules. Quantitative real-time polymerase chain reaction was performed in all 111 subjects. Results: A high EPA+DHA intake changed the expression of 1040 genes, whereas HOSF intake changed the expression of only 298 genes. EPA+DHA intake resulted in a decreased expression of genes involved in inflammatory- and atherogenic-related pathways, such as nuclear transcription factor B signaling, eicosanoid synthesis, scavenger receptor activity, adipogenesis, and hypoxia signaling. Conclusion: These results are the first to show that intake of EPA+DHA for 26 wk can alter the gene expression profiles of PBMCs to a more antiinflammatory and antiatherogenic status. This trial was registered at clinicaltrials.gov as NCT00124852
Functional characterization of Angptl4 protein
Lichtenstein, L.L. - \ 2009
Wageningen University. Promotor(en): Michael Muller, co-promotor(en): Sander Kersten. - [S.l. : S.n. - ISBN 9789085855033 - 118
vetzuren - genexpressie - lipidenmetabolisme - vasten - nutrigenomica - fatty acids - gene expression - lipid metabolism - fasting - nutrigenomics
Background: Elevated plasma triglycerides (TG) are increasingly recognized as a risk factor for atherosclerosis. A new adipocytokine was discovered by several groups which is referred to as Angptl4 (Angiopoietin-like protein 4). Angptl4 was recently identified as a major determinant of plasma TG levels in mice. Angptl4 is a 50 KDa secreted protein belonging to the family of fibrinogen/angiopoietin-like proteins.

Objective/Design: In order to characterize the metabolic function of Angptl4, we explored dietary modulation effects on transgenic mice overexpressing Angptl4.

Results: Taking advantage of the induction of Angptl4 by fasting, we showed that Angptl4 strongly inhibits LPL and HL activities. Later, we reported the development, validation and utilization of an ELISA assay to quantitatively assess Angptl4 levels in human plasma. Within an individual, Angptl4 levels rise in response to elevation of plasma free fatty acids. Furthermore, we address the function of Angptl4 in the heart. Dietary unsaturated fatty acids have a major impact on human health, which is likely achieved via changes in gene expression. Fatty acids regulate gene expression mainly via nuclear receptors, including the PPARs. Angptl4 appears to be regulated by dietary fat in a PPARb/d dependent, but in a PPARa independent way. Upregulation of Angptl4 resulted in decreased cardiac uptake of plasma TG-derived fatty acids and decreased fatty acid-induced oxidative stress and lipid peroxidation. Finally we investigated the function of Angptl4 in the intestine. Elevated saturated fat consumption is associated with increased risk for numerous chronic diseases, including inflammatory bowel disease, and obesity. Besides carrying out nutrient digestion and absorption, the GI-tract also produces a variety of hormones that play pivotal roles in nutrient handling and energy homeostasis. We report that Angptl4 is fat sensitive hormone produced by enteroendocrines cells. Noticeably, chronic saturated fat feeding led to complex and dramatic phenotype in Angptl4-/- mice. Angptl4-/- fed saturated fat developed a severe pathology leading to death. This lethal phenotype is preceded by excessive inflammation as shown by a dramatic hepatic acute phase response.

Conclusion: The data show that Angptl4 protects against the pro-inflammatory and ultimately lethal effects of chronic overconsumption of saturated fat.

Exploring the activation and function of PPARa and PPARß/d using genomics
Sanderson-Kjellberg, L.M. - \ 2009
Wageningen University. Promotor(en): Michael Muller, co-promotor(en): Sander Kersten. - [S.l. : S.n. - ISBN 9789085854555 - 200
lipidenmetabolisme - lever - vetzuren - genexpressie - nutrigenomica - lipid metabolism - liver - fatty acids - gene expression - nutrigenomics
For many tissues fatty acids represent the major source of fuel. In the past few decades it has become evident that in addition to their role as energy substrates, fatty acids also have an important signaling function by modulating transcription of genes. An important group of transcription factors involved in mediating the effects of dietary fatty acids on gene transcription are the Peroxisome Proliferator-Activated Receptors (PPARs). PPARs are members of the superfamily of nuclear hormone receptors and regulate genes involved in numerous important biological processes, ranging from lipid metabolism to inflammation and wound healing. In the liver the dominant PPAR isoform has been show to be PPARα, although PPARβ/δ and PPARγ are expressed in liver as well.

The aim of this thesis was to further characterize the role of PPARα and PPARβ/δ in hepatic metabolism and study their activation by fatty acids. Even though PPARα as gene regulator in liver has been well described, a complete overview of its target genes has been lacking so far. By combining several nutrigenomics tools, we succeeded in creating a comprehensive list of PPARα-regulated genes involved in lipid metabolism in liver. Additionally, by using a unique design where mice were fed synthetic triglycerides consisting of one type of fatty acid, we could distinguish between different types of dietary unsaturated fatty acids in their ability to activate PPARα. Although it is well known that PPARα plays an important role in liver during fasting, no direct in vivo evidence exists that circulating free fatty acids are able to ligand activate hepatic PPARα. In our studies, we found that upregulation of gene expression by PPARβ/δ is sensitive to circulating plasma free fatty acids whereas this is not the case for PPARα. Not much is known about the function of PPARβ/δ in the liver. In order to better understand the role of this nuclear receptor, we compared the effects of PPARα and PPARβ/δ deletion on whole genome gene regulation and plasma and liver metabolites. Our results revealed that PPARβ/δ does not mediate an adaptive response to fasting, and pointed to a role for PPARβ/δ in hepatic glucose- and lipoprotein metabolism.

In conclusion, this thesis contributes to the important work of mapping the molecular mechanisms dictating lipid metabolism in the liver. By using several nutrigenomics tools, we are able to show that PPARα is a key mediator of the effect of dietary fatty acids on hepatic gene expression. In addition, we better define the roles of PPARα and PPARβ/δ in hepatic metabolism and provide a new concept for functional differentiation between PPARs in liver.

Bayesian networks for omics data analysis
Gavai, A.K. - \ 2009
Wageningen University. Promotor(en): Jack Leunissen; Michael Muller, co-promotor(en): Guido Hooiveld; P.J.F. Lucas. - [S.l.] : S.n. - ISBN 9789085853909 - 98
bio-informatica - waarschijnlijkheidsmodellen - bayesiaanse theorie - netwerkanalyse - genexpressie - roken - vluchtige verbindingen - biochemische omzettingen - voedingsonderzoek bij de mens - genexpressieanalyse - microarrays - netwerken - nutrigenomica - bioinformatics - probabilistic models - bayesian theory - network analysis - gene expression - smoking - volatile compounds - biochemical pathways - human nutrition research - genomics - networks - nutrigenomics
This thesis focuses on two aspects of high throughput technologies, i.e. data storage and data analysis, in particular in transcriptomics and metabolomics. Both technologies are part of a research field that is generally called ‘omics’ (or ‘-omics’, with a leading hyphen), which refers to genomics, transcriptomics, proteomics, or metabolomics. Although these techniques study different entities (genes, gene expression, proteins, or metabolites), they all have in common that they use high-throughput technologies such as microarrays and mass spectrometry, and thus generate huge amounts of data. Experiments conducted using these technologies allow one to compare different states of a living cell, for example a healthy cell versus a cancer cell or the effect of food on cell condition, and at different levels.
The tools needed to apply omics technologies, in particular microarrays, are often manufactured by different vendors and require separate storage and analysis software for the data generated by them. Moreover experiments conducted using different technologies cannot be analyzed simultaneously to answer a biological question. Chapter 3 presents MADMAX, our software system which supports storage and analysis of data from multiple microarray platforms. It consists of a vendor-independent database which is tightly coupled with vendor-specific analysis tools. Upcoming technologies like metabolomics, proteomics and high-throughput sequencing can easily be incorporated in this system.
Once the data are stored in this system, one obviously wants to deduce a biological relevant meaning from these data and here statistical and machine learning techniques play a key role. The aim of such analysis is to search for relationships between entities of interest, such as genes, metabolites or proteins. One of the major goals of these techniques is to search for causal relationships rather than mere correlations. It is often emphasized in the literature that "correlation is not causation" because people tend to jump to conclusions by making inferences about causal relationships when they actually only see correlations. Statistics are often good in finding these correlations; techniques called linear regression and analysis of variance form the core of applied multivariate statistics. However, these techniques cannot find causal relationships, neither are they able to incorporate prior knowledge of the biological domain. Graphical models, a machine learning technique, on the other hand do not suffer from these limitations.
Graphical models, a combination of graph theory, statistics and information science, are one of the most exciting things happening today in the field of machine learning applied to biological problems (see chapter 2 for a general introduction). This thesis deals with a special type of graphical models known as probabilistic graphical models, belief networks or Bayesian networks. The advantage of Bayesian networks over classical statistical techniques is that they allow the incorporation of background knowledge from a biological domain, and that analysis of data is intuitive as it is represented in the form of graphs (nodes and edges). Standard statistical techniques are good in describing the data but are not able to find non-linear relations whereas Bayesian networks allow future prediction and discovering nonlinear relations. Moreover, Bayesian networks allow hierarchical representation of data, which makes them particularly useful for representing biological data, since most biological processes are hierarchical by nature. Once we have such a causal graph made either by a computer program or constructed manually we can predict the effects of a certain entity by manipulating the state of other entities, or make backward inferences from effects to causes. Of course, if the graph is big, doing the necessary calculations can be very difficult and CPU-expensive, and in such cases approximate methods are used.
Chapter 4 demonstrates the use of Bayesian networks to determine the metabolic state of feeding and fasting mice to determine the effect of a high fat diet on gene expression. This chapter also shows how selection of genes based on key biological processes generates more informative results than standard statistical tests. In chapter 5 the use of Bayesian networks is shown on the combination of gene expression data and clinical parameters, to determine the effect of smoking on gene expression and which genes are responsible for the DNA damage and the raise in plasma cotinine levels of blood of a smoking population. This study was conducted at Maastricht University where 22 twin smokers were profiled. Chapter 6 presents the reconstruction of a key metabolic pathway which plays an important role in ripening of tomatoes, thus showing the versatility of the use of Bayesian networks in metabolomics data analysis.
The general trend in research shows a flood of data emerging from sequencing and metabolomics experiments. This means that to perform data mining on these data one requires intelligent techniques that are computationally feasible and able to take the knowledge of experts into account to generate relevant results. Graphical models fit this paradigm well and we expect them to play a key role in mining the data generated from omics experiments.
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.
Een nieuwe vorm van E-voedingswetenschap
Kersten, A.H. ; Schrauwen, P. ; Müller, M.R. - \ 2008
Voeding Nu 10 (2008)12. - ISSN 1389-7608 - p. 19 - 19.
voedselwetenschappen - humane voeding - voedingsonderzoek - informatieverspreiding - internet - nutrigenomica - food sciences - human feeding - nutrition research - diffusion of information - nutrigenomics
De informatiemaatschappij zorgt voor een nieuwe vorm van voedingswetenschap op het gebied van nutrigenomics, Nutritional Science 2.0. Voor het vermeerderen van kennis op dit terrein is een vrije mondiale uitwisseling van data nodig die nog niet goed van de grond is gekomen
Statistical applications in nutrigenomics : analyzing multiple genes and proteins in relation to complex diseases in humans
Heidema, A.G. - \ 2008
Wageningen University. Promotor(en): Edith Feskens; E.C.M. Mariman, co-promotor(en): J.M.A. Boer. - [S.l.] : S.n. - ISBN 9789085852612 - 216
gegevensanalyse - statistische analyse - volksgezondheid - nutrigenomica - data analysis - statistical analysis - public health - nutrigenomics

Background
The recent advances in technology provide the possibility to obtain large genomic datasets that contain information on large numbers of variables, while the sample sizes are moderate to small. This has lead to statistical challenges in the analysis of multiple genes and proteins in relation to complex diseases. In this thesis approaches are investigated to analyze large genomic datasets, taking complex relationships between genes, proteins and complex diseases into account. These approaches are applied to real data to investigate whether biologically relevant information from the dataset could be obtained or whether models could be obtained that are useful for diagnostic or prognostic purposes.

Results
We developed a general framework for the analysis of genetic, transcriptomic and proteomic data to obtain insight in biological mechanisms. This framework consists of the following steps: detection of heterogeneity, dimensionality reduction to deal with the large numbers of variables, statistical interpretation and biological interpretation. We found that within this multi-step approach application of a combination of methods, including methods that take interactions into account, is useful within the dimensionality reduction step. In this way more information is captured compared to applying only one method. After selection of relevant variables in the dimensionality reduction step, applying visualization tools, e.g. the interaction entropy graph, together with traditional statistical methods showed to be helpful for statistical interpretation whether variables contribute by their main and/or interaction effect to the outcome of interest. In the last step, biological interpretation of the statistical results was facilitated by literature search, pathway analysis and database mining.

Discussion
The general framework discussed in this thesis provides the possibility to analyze large nutrigenomic datasets. Although the contribution of genomic research to public health is at the moment limited, new advances in genomic research, e.g. genome-wide association studies, statistical approaches as discussed in this thesis, are promising and genomic research might in the near future lead to applications that translate into improvement of public health.

Public acceptance of nutrigenomics-based personalised nutrition : exploring the future with experts and consumers
Ronteltap, A. - \ 2008
Wageningen University. Promotor(en): Hans van Trijp, co-promotor(en): Reint-Jan Renes. - [S.l.] : S.n. - ISBN 9789085049982 - 165
houding van consumenten - genotype-voeding interactie - voeding - consumentengedrag - innovatie adoptie - marketing - consumenten - consumentenvoorkeuren - deskundigen - voedingsmiddelen - nutrigenomica - consumer attitudes - genotype nutrition interaction - nutrition - consumer behaviour - innovation adoption - consumers - consumer preferences - experts - foods - nutrigenomics
Nutrigenomics is a recent discipline within nutrition sciences that aims at understanding how food components influence health status by affecting gene expression to eventually help maintain health and prevent disease. Nutrigenomics science has a potential consumer application in the form of so-called personalised nutrition: tailored dietary advice or even personalised food products that help consumers to select foods that are optimally aligned with their genetic constitution. However, due to the fact that nutrigenomics is an emerging science and personalised nutrition is still at an early stage of development, the views of both expert and lay stakeholders on the meaning, potential, and acceptability of personalised nutrition may still be divergent and developing. This dissertation takes up the challenge of understanding and anticipating public acceptance of nutrigenomics-based personalised nutrition. It aims to answer the central research question: What determines public acceptance of nutrigenomics-based personalised nutrition? For this purpose, three lines of research are
explored: development of a conceptual research framework from existing literature, expert views on the future of personalised nutrition, and consumer evaluations of different scenarios under which personalised nutrition might enter the market place.
The thesis’ theoretical contribution lies in an in-depth analysis of the concept of personalisation using marketing and consumer behaviour literature (chapter 2), and the development of a conceptual framework for consumer acceptance of food innovations (chapter 3). Empirically, results from a consumer study within a representative sample of Dutch consumers (chapter 5) reveal that freedom of choice, clear advantages, ease of applying personalised nutrition, and consensus among experts are important factors in enhancing consumer acceptance. However, the research in this thesis also shows that experts have not yet reached the necessary consensus on the scope and potential of nutrigenomics (chapter 4), and that experts do not expect that it will be easy for consumers to incorporate personalised nutrition into their daily lives (chapter 6). These, and other, issues can serve as inspiration for future research, as well as the further refinement of the generic framework for consumer acceptance of food innovations.
In conclusion, this thesis contributes to a better understanding of how public acceptance of the scientific innovation of nutrigenomics-based personalised nutrition comes about. It shows how issues critical for the further development of such an emerging science and the innovations arising from it can be systematically identified and addressed.

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