Artist Arne Hendriks is inspiring protein researchers
Hendriks, Arne ; Kleter, Gijs ; Esser, Diederik - \ 2020
Whole Grain Wheat Consumption Affects Postprandial Inflammatory Response in a Randomized Controlled Trial in Overweight and Obese Adults with Mild Hypercholesterolemia in the Graandioos Study
Hoevenaars, Femke P.M. ; Esser, Diederik ; Schutte, Sophie ; Priebe, Marion G. ; Vonk, Roel J. ; Brink, Willem J. van den; Kamp, Jan Willem van der; Stroeve, Johanna H.M. ; Afman, Lydia A. ; Wopereis, Suzan - \ 2019
The Journal of Nutrition 149 (2019)12. - ISSN 0022-3166 - p. 2133 - 2144.
(compromised) healthy subjects - challenge test - composite biomarkers - inflammation - liver - metabolic health - phenotypic flexibility - resilience - whole grain wheat
BACKGROUND: Whole grain wheat (WGW) consumption is associated with health benefits in observational studies. However, WGW randomized controlled trial (RCT) studies show mixed effects. OBJECTIVES: The health impact of WGW consumption was investigated by quantification of the body's resilience, which was defined as the "ability to adapt to a standardized challenge." METHODS: A double-blind RCT was performed with overweight and obese (BMI: 25-35 kg/m2) men (n = 19) and postmenopausal women (n = 31) aged 45-70 y, with mildly elevated plasma total cholesterol (>5 mmol/L), who were randomly assigned to either 12-wk WGW (98 g/d) or refined wheat (RW). Before and after the intervention a standardized mixed-meal challenge was performed. Plasma samples were taken after overnight fasting and postprandially (30, 60, 120, and 240 min). Thirty-one biomarkers were quantified focusing on metabolism, liver, cardiovascular health, and inflammation. Linear mixed-models evaluated fasting compared with postprandial intervention effects. Health space models were used to evaluate intervention effects as composite markers representing resilience of inflammation, liver, and metabolism. RESULTS: Postprandial biomarker changes related to liver showed decreased alanine aminotransferase by WGW (P = 0.03) and increased β-hydroxybutyrate (P = 0.001) response in RW. Postprandial changes related to inflammation showed increased C-reactive protein (P = 0.001), IL-6 (P = 0.02), IL-8 (P = 0.007), and decreased IL-1B (P = 0.0002) in RW and decreased C-reactive protein (P < 0.0001), serum amyloid A (P < 0.0001), IL-8 (P = 0.02), and IL-10 (P < 0.0001) in WGW. Health space visualization demonstrated diminished inflammatory (P < 0.01) and liver resilience (P < 0.01) by RW, whereas liver resilience was rejuvenated by WGW (P < 0.05). CONCLUSIONS: Twelve-week 98 g/d WGW consumption can promote liver and inflammatory resilience in overweight and obese subjects with mildly elevated plasma cholesterol. The health space approach appeared appropriate to evaluate intervention effects as composite markers. This trial was registered at www.clinicaltrials.gov as NCT02385149.
Natural choline from egg yolk phospholipids is more efficiently absorbed compared with choline bitartrate; outcomes of a randomized trial in healthy adults
Smolders, Lotte ; Wit, Nicole J.W. de; Balvers, Michiel G.J. ; Obeid, Rima ; Vissers, Marc M.M. ; Esser, Diederik - \ 2019
Nutrients 11 (2019)11. - ISSN 2072-6643
Absorption - Choline - DHA - Natural - Phospholipids
Choline is a vitamin-like essential nutrient, important throughout one’s lifespan. Therefore, choline salts are added to infant formula, supplements and functional foods. However, if choline is present in a natural form, e.g. bound to phospholipids, it may be more efficiently absorbed. The study’s aim was to evaluate if choline uptake is improved after consumption of an egg yolk phospholipid drink, containing 3 g of phospholipid bound choline, compared to a control drink with 3 g of choline bitartrate. We performed a randomized, double blind, cross-over trial with 18 participants. Plasma choline, betaine and dimethylglycine concentrations were determined before and up to six hours after consumption of the drinks. The plasma choline response, as determined by the incremental area under the curve, was four times higher after consumption of the egg yolk phospholipid drink compared with the control drink (p < 0.01). Similar outcomes were also observed for choline’s main metabolites, betaine (p < 0.01) and dimethylglycine (p = 0.01). Consumption of natural choline from egg yolk phospholipids improved choline absorption compared to consumption of chemically produced choline bitartrate. This information is of relevance for the food industry, instead of adding choline-salts, adding choline from egg yolk phospholipids can improve choline uptake and positively impact health.
Remote sensing and signaling in kidney proximal tubules stimulates gut microbiome-derived organic anion secretion
Jansen, Jitske ; Jansen, Katja ; Neven, Ellen ; Poesen, Ruben ; Othman, Amr ; Mil, Alain van; Sluijter, Joost ; Torano, Javier Sastre ; Zaal, Esther A. ; Berkers, Celia R. ; Esser, Diederik ; Wichers, Harry J. ; Ede, Karin van; Duursen, Majorie van; Burtey, Stéphane ; Verhaar, Marianne C. ; Meijers, Björn ; Masereeuw, Rosalinde - \ 2019
Proceedings of the National Academy of Sciences of the United States of America 116 (2019)32. - ISSN 0027-8424 - p. 16105 - 16110.
Indoxyl sulfate - Kidney proximal tubule - Organic anion transporter 1 - Remote sensing and signaling
Membrane transporters and receptors are responsible for balancing nutrient and metabolite levels to aid body homeostasis. Here, we report that proximal tubule cells in kidneys sense elevated endogenous, gut microbiome-derived, metabolite levels through EGF receptors and downstream signaling to induce their secretion by up-regulating the organic anion transporter-1 (OAT1). Remote metabolite sensing and signaling was observed in kidneys from healthy volunteers and rats in vivo, leading to induced OAT1 expression and increased removal of indoxyl sulfate, a prototypical microbiome-derived metabolite and uremic toxin. Using 2D and 3D human proximal tubule cell models, we show that indoxyl sulfate induces OAT1 via AhR and EGFR signaling, controlled by miR-223. Concomitantly produced reactive oxygen species (ROS) control OAT1 activity and are balanced by the glutathione pathway, as confirmed by cellular metabolomic profiling. Collectively, we demonstrate remote metabolite sensing and signaling as an effective OAT1 regulation mechanism to maintain plasma metabolite levels by controlling their secretion.
Extrinsic wheat fibre consumption enhances faecal bulk and stool frequency; A randomized controlled trial
Wit, Nicole De; Esser, Diederik ; Siebelink, Els ; Fischer, Anne ; Sieg, Juergen ; Mes, Jurriaan - \ 2019
Food & Function 10 (2019)2. - ISSN 2042-6496 - p. 646 - 651.
The beneficial effect of wheat fibres on faecal bulk and stool pattern has mainly been observed with intact wheat fibres. This study investigates the effect of extrinsic wheat fibre (VITACEL® wheat fibre), which can be easily incorporated in many food products, on faecal bulk, stool pattern, gastrointestinal complaints, satiety and food liking. In a double-blind randomized crossover trial, healthy male volunteers received meal boxes for 10 days, containing various food products enriched with extrinsic wheat fibre (∼20 grams of additional fibre per day) or control food products containing conventional levels of fibre with similar taste, appearance and caloric values. Meal boxes were integrated in the normal dietary pattern. Stool frequency, stool consistency, gastrointestinal complaints, satiety and product liking were assessed daily, and the last 5 days of each intervention, participants collected all their faeces to analyse faecal bulk. We found that consumption of extrinsic wheat fibre-enriched products significantly enhanced faecal bulk; faecal wet and dry weight showed a 1.41 ± 0.1 and 1.55 ± 0.1 times increase compared to control, respectively (p < 0.01). Extrinsic wheat fibre intervention furthermore increased stool frequency (1.3 ± 0.1 defecations per day compared to 1.1 ± 0.1 defecations per day during control diet, p < 0.05), but did not affect stool consistency, satiety, gastrointestinal complaints or product liking. So, increased consumption of extrinsic wheat fibre enhances faecal bulk and stool frequency. As this extrinsic wheat fibre can be easily incorporated in many food products without affecting appearance or taste, it might facilitate the increase of overall fibre intake and subsequently improve (intestinal) health.
A 12-wk whole-grain wheat intervention protects against hepatic fat : the Graandioos study, a randomized trial in overweight subjects
Schutte, Sophie ; Esser, Diederik ; Hoevenaars, Femke P.M. ; Hooiveld, Guido J.E.J. ; Priebe, Marion G. ; Vonk, Roel J. ; Wopereis, Suzan ; Afman, Lydia A. - \ 2018
American Journal of Clinical Nutrition 108 (2018)6. - ISSN 0002-9165 - p. 1264 - 1274.
Background: Whole-grain wheat (WGW) is described as nutritionally superior to refined wheat (RW) and thus advocated as the healthy choice, although evidence from intervention studies is often inconsistent. The liver, as the central organ in energy metabolism, might be an important target organ for WGW interventions. Objective: The aim of this study was to investigate the potential benefits of WGW consumption compared with RW consumption on liver health and associated parameters. Design: We performed a double-blind, parallel trial in which 50 overweight 45- to 70-y-old men and postmenopausal women were randomly allocated to a 12-wk intervention with either WGW (98 g/d) or RW (98 g/d) products. Before and after the intervention we assessed intrahepatic triglycerides (IHTGs) and fat distribution by proton magnetic resonance spectroscopy/magnetic resonance imaging, fecal microbiota composition, adipose tissue gene expression, and several fasting plasma parameters, as well as postprandial plasma lipids after a mixed meal. Results: Fasting plasma cholesterol, triglycerides, nonesterified fatty acids, and insulin were not affected by RW or WGW intervention. We observed a substantial increase of 49.1% in IHTGs in the RW when compared with the WGW group (P = 0.033). Baseline microbiota composition could not predict the increase in IHTGs after RW, but gut microbiota diversity decreased in the RW group when compared with the WGW group (P = 0.010). In the WGW group, we observed increased postprandial triglyceride levels compared with the RW group (P = 0.020). In addition, the WGW intervention resulted in a trend towards lower fasting levels of the liver acute-phase proteins serum amyloid A (P = 0.057) and C-reactive protein (P = 0.064) when compared to the RW intervention. Conclusions: A 12-wk RW intervention increases liver fat and might contribute to the development of nonalcoholic fatty liver disease, whereas a 12-wk 98-g/d WGW intervention prevents a substantial increase in liver fat. Our results show that incorporating feasible doses of WGW in the diet at the expense of RW maintains liver health. The study was registered at clinicaltrials.gov as NCT02385149.
Pure epicatechin and inflammatory gene expression profiles in circulating immune cells in (pre) hypertensive adults; a randomized double-blind, placebo-controlled, crossover trial
Esser, D. ; Dower, J.I. ; Matualatupauw, J.C. ; Geleijnse, J.M. ; Kromhout, D. ; Hollman, P.C.H. ; Afman, L.A. - \ 2018
Homo sapiens - GSE84453 - PRJNA329219
Introduction: There is increasing evidence that consumption of cocoa products have a beneficial effect on cardio-metabolic health, but the underlying mechanisms remain unclear. Cocoa contains a complex mixture of flavan-3-ols. Epicatechin, a major monomeric flavan-3-ol, is considered to contribute to the cardio-protective effects of cocoa. We investigated effects of pure epicatechin supplementation on whole genome gene expression profiles of circulating immune cells. Methods: In a randomized, double blind, placebo-controlled cross-over trial, 37 (pre)hypertensive (40-80y) subjects received two 4-week interventions; epicatechin (100mg/day) or placebo with a wash-out period of 4-week between both interventions. Whole genome gene expression profiles of peripheral blood mononuclear cells were determined before and after both interventions. Results: After epicatechin supplementation 1180 genes were significantly regulated, of which 234 were also significantly regulated compared to placebo. Epicatechin supplementation up-regulated gene sets involved in transcription/translation and tubulin folding and down-regulated gene sets involved in inflammation. Only a few genes within these regulated gene sets were actually significantly changed upon epicatechin supplementation. Upstream regulators that were shown to be inhibited were classified as cytokine or inflammatory type molecules. Conclusion: Pure epicatechin supplementation modestly reduced gene expression related to inflammation signalling routes in circulating immune cells. These routes are known to play a role in cardiovascular health.
Pure flavonoid epicatechin and whole genome gene expression profiles in circulating immune cells in adults with elevated blood pressure: A randomised double-blind, placebo-controlled, crossover trial
Esser, Diederik ; Geleijnse, Johanna M. ; Matualatupauw, Juri C. ; Dower, James I. ; Kromhout, Daan ; Hollman, Peter C.H. ; Afman, Lydia A. - \ 2018
PLoS ONE 13 (2018)4. - ISSN 1932-6203 - 15 p.
Cocoa consumption has beneficial cardiometabolic effects, but underlying mechanisms remain unclear. Epicatechin, the cocoa major monomeric flavan-3-ol, is considered to contribute to these cardio-protective effects. We investigated effects of pure epicatechin supplementation on gene expression profiles of immune cells in humans. In a double blind, placebo-controlled cross-over trial, 32 (pre)hypertensive subjects aged 30 to 80, received two 4-week interventions, i.e. epicatechin (100mg/day) or placebo with a 4-week wash-out between interventions. Gene expression profiles of peripheral blood mononuclear cells were determined before and after both interventions. Epicatechin regulated 1180 genes, of which 234 differed from placebo. Epicatechin upregulated gene sets involved in transcription and tubulin folding and downregulated gene sets involved in inflammation, PPAR signalling and adipogenesis. Several negatively enriched genes within these gene sets were involved in insulin signalling. Most inhibited upstream regulators within the epicatechin intervention were cytokines or involved in inflammation. No upstream regulators were identified compared to placebo. Epicatechin, a cocoa flavan-3-ol, reduces gene expression involved in inflammation, PPAR-signalling and adipogenesis in immune cells. Effects were mild but our findings increase our understanding and provide new leads on how epicatechin rich products like cocoa may affect immune cells and exert cardiometabolic protective effects.
Weight loss moderately affects the mixed meal challenge response of the plasma metabolome and transcriptome of peripheral blood mononuclear cells in abdominally obese subjects
Fazelzadeh, Parastoo ; Hangelbroek, Roland W.J. ; Joris, Peter J. ; Schalkwijk, Casper G. ; Esser, Diederik ; Afman, Lydia ; Hankemeier, Thomas ; Jacobs, Doris M. ; Mihaleva, Velitchka V. ; Kersten, Sander ; Duynhoven, John van; Boekschoten, Mark V. - \ 2018
Metabolomics 14 (2018)4. - ISSN 1573-3882
Metabolic health - Mixed-meal challenge - Phenotype shift
Introduction: The response to dietary challenges has been proposed as a more accurate measure of metabolic health than static measurements performed in the fasted state. This has prompted many groups to explore the potential of dietary challenge tests for assessment of diet and lifestyle induced shifts in metabolic phenotype. Objectives: We examined whether the response to a mixed-meal challenge could provide a readout for a weight loss (WL)-induced phenotype shift in abdominally obese male subjects. The underlying assumption of a mixed meal challenge is that it triggers all aspects of phenotypic flexibility and provokes a more prolonged insulin response, possibly allowing for better differentiation between individuals. Methods: Abdominally obese men (n = 29, BMI = 30.3 ± 2.4 kg/m2) received a mixed-meal challenge prior to and after an 8-week WL or no-WL control intervention. Lean subjects (n = 15, BMI = 23.0 ± 2.0 kg/m2) only received the mixed meal challenge at baseline to have a benchmark for WL-induced phenotype shifts. Results: Levels of several plasma metabolites were significantly different between lean and abdominally obese at baseline as well as during postprandial metabolic responses. Genes related to oxidative phosphorylation in peripheral blood mononuclear cells (PBMCs) were expressed at higher levels in abdominally obese subjects as compared to lean subjects at fasting, which was partially reverted after WL. The impact of WL on the postprandial response was modest, both at the metabolic and gene expression level in PBMCs. Conclusion: We conclude that mixed-meal challenges are not necessarily superior to measurements in the fasted state to assess metabolic health. Furthermore, the mechanisms accounting for the observed differences between lean and abdominally obese in the fasted state are different from those underlying the dissimilarity observed during the postprandial response.
High fat challenges with different fatty acids affect distinct atherogenic gene expression pathways in immune cells from lean and obese subjects
Esser, Diederik ; Afman, Lydia - \ 2015
GSE53232 - Homo sapiens - GSE53232 - Homo sapiens - PRJNA231185
Early perturbations in vascular health can be detected by imposing subjects to a high fat (HF) challenge and measure response capacity. Subtle responses can be determined by assessment of whole-genome transcriptional changes. We aimed to magnify differences in health by comparing gene-expression changes in peripheral blood mononuclear cells (PBMCs) towards a high MUFA or SFA challenge between subjects with different cardiovascular disease risk profiles and to identify fatty-acid specific gene-expression pathways. METHODS AND RESULTS: In a cross-over study, 17 lean and 15 obese men (50-70y) received two 95g fat shakes, high in SFAs or MUFAs. PBMC gene-expression profiles were assessed fasted and 4h postprandially. Comparisons were made between groups and shakes. During fasting, 294 genes were significantly different expressed between lean and obese. The challenge increased differences to 607 genes after SFA and 2516 genes after MUFA. In both groups, SFA decreased expression of cholesterol biosynthesis and uptake genes and increased cholesterol efflux genes. MUFA increased inflammatory genes and PPARα targets involved in β-oxidation. CONCLUSION: Based upon gene-expression changes, we conclude that a HF challenge magnifies differences in health, especially after MUFA. Our findings also demonstrate how SFAs and MUFAs exert distinct effects on lipid handling pathways in immune cells.
High fat challenges with different fatty acids affect distinct atherogenic gene expression pathways in immune cells from lean and obese subjects
Esser, D. ; Dijk, S.J. van; Oosterink, E. ; Lopez, S. ; Muller, M.R. ; Afman, L.A. - \ 2015
Molecular Nutrition & Food Research 59 (2015)8. - ISSN 1613-4125 - p. 1563 - 1572.
triglyceride-rich lipoproteins - blood mononuclear-cells - men - atherosclerosis - inflammation - activation - receptors - adherence - profiles - alpha
Scope - Early perturbations in vascular health can be detected by imposing subjects to a high fat (HF) challenge and measure response capacity. Subtle responses can be determined by assessment of whole-genome transcriptional changes. We aimed to magnify differences in health by comparing gene-expression changes in peripheral blood mononuclear cells toward a high MUFA or saturated fatty acids (SFA) challenge between subjects with different cardiovascular disease risk profiles and to identify fatty acid specific gene-expression pathways. Methods and results -In a cross-over study, 17 lean and 15 obese men (50–70 years) received two 95 g fat shakes, high in SFAs or MUFAs. Peripheral blood mononuclear cell gene-expression profiles were assessed fasted and 4-h postprandially. Comparisons were made between groups and shakes. During fasting, 294 genes were significantly differently expressed between lean and obese. The challenge increased differences to 607 genes after SFA and 2516 genes after MUFA. In both groups, SFA decreased expression of cholesterol biosynthesis and uptake genes and increased cholesterol efflux genes. MUFA increased inflammatory genes and PPAR-a targets involved in ß-oxidation. Conclusion - Based upon gene-expression changes, we conclude that an HF challenge magnifies differences in health, especially after MUFA. Our findings also demonstrate how SFAs and MUFAs exert distinct effects on lipid handling pathways in immune cells.
Dark chocolate consumption improves leukocyte adhesion factors and vascular function in overweight men
Esser, D. ; Mars, M. ; Oosterink, E. ; Stalmach, A. ; Müller, M.R. ; Afman, L.A. - \ 2014
FASEB Journal 28 (2014)3. - ISSN 0892-6638 - p. 1464 - 1473.
flavanol-rich cocoa - endothelial function - mediated vasodilatation - cardiovascular health - postprandial lipemia - repeated exposure - metaanalysis - disease - atherosclerosis - prediction
Flavanol-enriched chocolate consumption increases endothelium-dependent vasodilation. Most research so far has focused on flow-mediated dilation (FMD) only; the effects on other factors relevant to endothelial health, such as inflammation and leukocyte adhesion, have hardly been addressed. We investigated whether consumption of regular dark chocolate also affects other markers of endothelial health, and whether chocolate enrichment with flavanols has additional benefits. In a randomized double-blind crossover study, the effects of acute and of 4 wk daily consumption of high flavanol chocolate (HFC) and normal flavanol chocolate (NFC) on FMD, augmentation index (AIX), leukocyte count, plasma cytokines, and leukocyte cell surface molecules in overweight men (age 45–70 yr) were investigated. Sensory profiles and motivation scores to eat chocolate were also collected. Findings showed that a 4 wk chocolate intake increased FMD by 1%, which was paralleled by a decreased AIX of 1%, decreased leukocyte cell count, decreased plasma sICAM1 and sICAM3, and decreased leukocyte adhesion marker expression (P
Postprandial fatty acid specific changes in circulating oxylipins in lean and obese men after high-fat challenge tests
Strassburg, K. ; Esser, D. ; Vreeken, R.J. ; Hankemeier, T. ; Müller, M.R. ; Duynhoven, J.P.M. van; Golde, J. van; Dijk, S.J. van; Afman, L.A. ; Jacobs, D.M. - \ 2014
Molecular Nutrition & Food Research 58 (2014)3. - ISSN 1613-4125 - p. 591 - 600.
eicosanoid biology - markers - health
Scope Circulating oxylipins may affect peripheral tissues and are assumed to play an important role in endothelial function. They are esterified in triglyceride-rich lipoproteins that are increased after a high-fat (HF) meal, depending on BMI and fatty acid (FA) type. Yet, it is unclear which oxylipins appear in circulation after HF meals differing in FA composition. Methods and results In a double-blind randomized crossover challenge study, we characterized the postprandial oxylipin response after different HF challenges in lean and obese men receiving HF milkshakes, either high in saturated FAs (SFA), monounsaturated FAs (MUFA), or omega 3 (n-3) polyunsaturated FAs (PUFA). Plasma oxylipin profiles were significantly altered at 2 and 4 h after shake consumption when compared to baseline. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) derived oxylipins increased after n-3 PUFA shake consumption. MUFA shake consumption increased levels of cytochrome P450 mediated oxylipins. SFA shake consumption led to strong increases in linoleic acid (LA) derived HODEs. No differences were observed between lean and obese individuals at baseline and after any shake consumption. Conclusion e are the first demonstrating acute effects on circulating oxylipins after HF meal challenges. These changes were strongly influenced by different dietary FAs and may affect endothelial function.
A high-fat SFA, MUFA, or n3 PUFA challenge affects the vascular response and initiates an activated state of cellular adherence in lean and obese middle-aged men
Esser, D. ; Dijk, S.J. van; Oosterink, E. ; Müller, M.R. ; Afman, L.A. - \ 2013
The Journal of Nutrition 143 (2013)6. - ISSN 0022-3166 - p. 843 - 851.
triglyceride-rich lipoproteins - postprandial lipemia - nonfasting triglycerides - cardiovascular-disease - arterial stiffness - oxidative stress - healthy-men - young men - dietary - women
BMI and fatty acid type affect postprandial metabolic TG responses, but whether these factors also affect vascular, inflammatory, and leukocyte adherence responses remains unclear. We therefore compared those postprandial responses between lean and obese men after 3 high-fat challenges differing in fatty acid composition. In a crossover double-blind study, 18 lean (BMI: 18–25 kg/m2) and 18 obese (BMI >29 kg/m2) middle-aged men received 3 isocaloric high-fat milkshakes containing 95 g fat (88% of energy), either high in SFAs (54% of energy/total fat), MUFAs (83% of energy/total fat), or n3 (omega-3) PUFAs (40% of energy/total fat). Hemodynamics, augmentation index (AIX), leukocyte cell surface adhesion markers, and plasma cytokines involved in vascular adherence, coagulation, and inflammation were measured before and after consumption of the milkshakes. In both groups and after all shakes were consumed, AIX decreased; plasma soluble intercellular adhesion molecule (sICAM) 1, sICAM3, soluble vascular cell adhesion molecule (sVCAM) 1, and interleukin-8 increased; monocyte CD11a, CD11b, and CD621 expression increased; neutrophil CD11a, CD11b, and CD621 expression increased; and lymphocyte CD62l expression increased (P <0.05). Lymphocyte CD11a and CD11b expression decreased in lean participants after consumption of all shakes but did not change in obese participants (P <0.05). Obese participants had a less pronounced decrease in heart rate after the consumption of all shakes (P <0.05). MUFA consumption induced a more pronounced decrease in blood pressure and AIX compared with the other milkshakes in both lean and obese participants (P <0.05). High-fat consumption initiates an activated state of cellular adherence and an atherogenic milieu. This response was independent of fatty acid type consumed or of being lean or obese, despite the clear differences in postprandial TG responses between the groups and different milkshakes. These findings suggest that in addition to increased TGs, other mechanisms are involved in the high-fat consumption–induced activated state of cellular adherence.
Vascular and inflammatory high fat meal responses in young healthy men; a discriminative role of IL-8 observed in a randomized trial
Esser, D. ; Oosterink, E. ; Roodt, J. op 't; Henry, R.M.A. ; Stehouwer, C.D.A. ; Müller, M.R. ; Afman, L.A. - \ 2013
PLoS ONE 8 (2013)2. - ISSN 1932-6203 - 9 p.
postprandial endothelial function - flow-mediated vasodilation - oxidative stress - arterial stiffness - normal-weight - humans - dysfunction - reactivity - interleukin-8 - activation
Background High fat meal challenges are known to induce postprandial low-grade inflammation and endothelial dysfunction. This assumption is largely based on studies performed in older populations or in populations with a progressed disease state and an appropriate control meal is often lacking. Young healthy individuals might be more resilient to such challenges. We therefore aimed to characterize the vascular and inflammatory response after a high fat meal in young healthy individuals. Methods In a double-blind randomized cross-over intervention study, we used a comprehensive phenotyping approach to determine the vascular and inflammatory response after consumption of a high fat shake and after an average breakfast shake in 20 young healthy subjects. Both interventions were performed three times. Results Many features of the vascular postprandial response, such as FMD, arterial stiffness and micro-vascular skin blood flow were not different between shakes. High fat/high energy shake consumption was associated with a more pronounced increase in blood pressure, heart rate, plasma concentrations of IL-8 and PBMCs gene expression of IL-8 and CD54 (ICAM-1), whereas plasma concentrations of sVCAM1 were decreased compared to an average breakfast. Conclusion Whereas no difference in postprandial response were observed on classical markers of endothelial function, we did observe differences between consumption of a HF/HE and an average breakfast meal on blood pressure and IL-8 in young healthy volunteers. IL-8 might play an important role in dealing with high fat challenges and might be an early marker for endothelial stress, a stage preceding endothelial dysfunction
High fat challenges and detection of early perturbations in endothelial health : the use of a comprehensive phenotyping approach
Esser, D. - \ 2013
Wageningen University. Promotor(en): Michael Muller, co-promotor(en): Lydia Afman. - S.l. : s.n. - ISBN 9789461735911 - 168
endotheel - vetconsumptie - voedingsvet - lipidenmetabolisme - chocolade - endothelium - fat consumption - dietary fat - lipid metabolism - chocolate
Background:Cardiovascular disease (CVD) is one of the leading causes of morbidity and mortality worldwide. One of the pathophysiology’s that play a pivotal role in the development and progression of CVD is a dysfunctional endothelium. An important lifestyle risk factor for endothelial dysfunction is the diet and several nutrients have been classified to be either beneficial or harmful for the endothelium. Although CVD usually affects middle-aged or older adults, the onset of endothelial dysfunction begins in early life, emphasising the need for primary prevention. We therefore aimed to identify markers of early perturbations in endothelial health by using dietary stressors, e.g. high fat (HF) challenge test. Thereafter we aimed to evaluate if the potential early markers are reversible and can be improved after an intervention with a dietary anti-stressor.
Methods:First we validated the HF challenge test as a tool to trigger the endothelial response capacity. For that purpose, we compared the postprandial response after a HF shake with an average breakfast shake in young healthy men by assessing several plasma markers and functional measures of endothelial function. To identify new markers for early perturbations in endothelial health and to optimized the HF challenge test we applied three HF challenges differing in fatty acid type in two populations of middle-aged men, i.e. one at high- and one at low risk for developing CVD and characterized the postprandial response by applying high-throughput metabolomic and transcriptomic tools next to an extensive phenotyping of vascular function and vascular health parameters. Lastly, we evaluated if the, in the studies above, identified potential early biomarker profile is reversible and can be improved after an intervention with a dietary anti-stressor by means of a high flavanol chocolate intervention.
Results:In young men, we observed that a HF challenge decreased flow mediated dilation (FMD), but this decrease was also found after the consumption of an average breakfast shake. IL-8 concentrations were more pronouncedly increased after HF shake consumption compared to an average breakfast control shake. In middle-aged men, a HF challenge decreased the augmentation index (AIX) and elicited an activated state of cellular adherence in the circulation as determined by increased plasma soluble adhesion molecules, increased leukocyte cell surface integrin and selectin expression and increased number of leukocytes. A challenge high in mono-unsaturated fatty acids (MUFAs) elicited the highest postprandial triglyceride (TG) concentrations and the most pronounced effects on AIX. By applying high-throughput metabolomic tools, we observed that oxylipin profiles were affected by the HF challenge and that these changes were depended on dietary fatty acid composition. Application of transcriptome profiling revealed that changes in peripheral blood mononuclear cell (PBMC) gene expression profiles after a HF challenge test were different between lean and obese subjects, with the most deviating effect after MUFA intake. The saturated fatty acid (SFA) shake decreased the expression of genes involved in cholesterol uptake and cholesterol biosynthesis and increased expression of genes involved in cholesterol efflux. MUFA increased expression of inflammatory genes and of peroxisome proliferator-activated receptor α (PPARα) target genes involved in β-oxidation. 4-week daily intake of a dietary anti-stressor, e.g. dark chocolate, increased fasting FMD and decreased AIX, and elicited a less activated state of cellular adherence, as determined by a decrease in plasma soluble adhesion molecules, a decrease in leukocyte cell surface integrin and selectin expression and a decrease in the number of leukocytes.
Conclusions:In this thesis we extensively characterized the postprandial response to a HF challenge in human subjects with different disease risk profiles and optimized the HF challenge test. We identified MUFAs as most potent fatty acids to trigger the vascular and cellular response capacity, which makes it the optimal fatty acid type to use in a HF challenge test. We demonstrated that besides functional measures of vascular function, also plasma and cellular factors involved in leukocyte adhesion to the endothelium are adversely affected by dietary stressors and are beneficially affected by a dietary anti-stressor. Therefore, we conclude that endothelial health can be more comprehensively measured by means of a biomarker profile consisting not only of the vascular function measures FMD and AIX, but also of a subset of soluble adhesion molecules in the plasma, leukocyte counts and cell surface integrin and selectin expression. To identify potential new leads for biomarkers, we applied whole genome gene expression profiling, combined with the HF challenge test which enabled us to detect small differences in health status. Furthermore, we identified metabolic and inflammatory pathways that are specifically affected by either MUFAs or SFAs. These findings increased our understanding on how a SFA or MUFA challenge exert their distinct effects on stress related and metabolic compensatory cellular processes and provided us with new potential leads to detect early perturbations in endothelial health.
Responses to high-fat challenges varying in fat type in subjects with different metabolic risk phenotypes: a randomized trial
Dijk, S.J. van; Mensink, M.R. ; Esser, D. ; Feskens, E.J.M. ; Muller, M.R. ; Afman, L.A. - \ 2012
PLoS ONE 7 (2012)7. - ISSN 1932-6203
gene-expression profiles - blood mononuclear-cells - postprandial lipemia - nonfasting triglycerides - insulin sensitivity - visceral adiposity - glucose-tolerance - rich lipoproteins - healthy-subjects - men
Background The ability of subjects to respond to nutritional challenges can reflect the flexibility of their biological system. Nutritional challenge tests could be used as an indicator of health status but more knowledge on metabolic and immune responses of different subjects to nutritional challenges is needed. The aim of this study was to compare the responses to high-fat challenges varying in fat type in subjects with different metabolic risk phenotypes. Methodology/Principal Findings In a cross-over design 42 men (age 50–70 y) consumed three high-fat shakes containing saturated fat (SFA), monounsaturated fat (MUFA) or n-3 polyunsaturated (PUFA). Men were selected on BMI and health status (lean, obese or obese diabetic) and phenotyped with MRI for adipose tissue distribution. Before and 2 and 4 h after shake consumption blood was drawn for measurement of expression of metabolic and inflammation-related genes in peripheral blood mononuclear cells (PBMCs), plasma triglycerides (TAG), glucose, insulin, cytokines and ex vivo PBMC immune response capacity. The MUFA and n-3 PUFA challenge, compared to the SFA challenge, induced higher changes in expression of inflammation genes MCP1 and IL1ß in PBMCs. Obese and obese diabetic subjects had different PBMC gene expression and metabolic responses to high-fat challenges compared to lean subjects. The MUFA challenge induced the most pronounced TAG response, mainly in obese and obese diabetic subjects. Conclusion/Significance The PBMC gene expression response and metabolic response to high-fat challenges were affected by fat type and metabolic risk phenotype. Based on our results we suggest using a MUFA challenge to reveal differences in response capacity of subjects
Functional curation of the Sulfolobus solfataricus P2 and S. acidocaldarius 98-3 complete genome sequences
Esser, D. ; Kouril, T. ; Zaparty, M. ; Sierocinski, P. ; Oost, J. van der; Makarova, K.S. ; Siebers, B. - \ 2011
Extremophiles 15 (2011)6. - ISSN 1431-0651 - p. 711 - 712.
nonautonomous mobile elements - archaeal genomes - genus sulfolobus - temperature - model
The thermoacidophiles Sulfolobus solfataricus P2 and S. acidocaldarius 98-3 are considered key model organisms representing a major phylum of the Crenarchaeota. Because maintaining current, accurate genome information is indispensable for modern biology, we have updated gene function annotation using the arCOGs database, plus other available functional, structural and phylogenetic information. The goal of this initiative is continuous improvement of genome annotation with the support of the Sulfolobus research community
"Hot standards" for the thermoacidophilic archaeon Sulfolobus solfataricus
Zaparty, M. ; Esser, D. ; Gertig, S. ; Haferkamp, P. ; Kouril, T. ; Sierocinski, P. ; Pham, T.K. ; Manica, A. ; Reimann, J. ; Schreiber, K. ; Teichmann, D. ; Wolferen, M.E. van; Jan, M. von; Wieloch, P. ; Albers, S.V. ; Driessen, A.J.M. ; Klenk, H.P. ; Schleper, C. ; Schomburg, D. ; Oost, J. van der; Wright, P.C. ; Siebers, B. - \ 2010
Extremophiles 14 (2010)1. - ISSN 1431-0651 - p. 119 - 142.
entner-doudoroff pathway - central carbohydrate-metabolism - dna microarray analysis - hyperthermophilic archaeon - membrane proteome - genus sulfolobus - high-temperature - systems biology - silicon cell - key-enzyme
Within the archaea, the thermoacidophilic crenarchaeote Sulfolobus solfataricus has become an important model organism for physiology and biochemistry, comparative and functional genomics, as well as, more recently also for systems biology approaches. Within the Sulfolobus Systems Biology ("SulfoSYS")-project the effect of changing growth temperatures on a metabolic network is investigated at the systems level by integrating genomic, transcriptomic, proteomic, metabolomic and enzymatic information for production of a silicon cell-model. The network under investigation is the central carbohydrate metabolism. The generation of high-quality quantitative data, which is critical for the investigation of biological systems and the successful integration of the different datasets, derived for example from high-throughput approaches (e.g., transcriptome or proteome analyses), requires the application and compliance of uniform standard protocols, e.g., for growth and handling of the organism as well as the "-omics" approaches. Here, we report on the establishment and implementation of standard operating procedures for the different wet-lab and in silico techniques that are applied within the SulfoSYS-project and that we believe can be useful for future projects on Sulfolobus or (hyper)thermophiles in general. Beside established techniques, it includes new methodologies like strain surveillance, the improved identification of membrane proteins and the application of crenarchaeal metabolomics