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.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Non-invasive continuous real-time in vivo analysis of microbial hydrogen production shows adaptation to fermentable carbohydrates in mice
Fernández Calleja, J.M.S. ; Konstanti, Prokopis ; Swarts, J.J.M. ; Bouwman, L.M.S. ; Garcia-Campayo, Vicenta ; Billecke, Nils ; Oosting, Annemarie ; Smidt, H. ; Keijer, J. ; Schothorst, E.M. van - \ 2018
PRJEB23475 - ERP105229
The gut microbiome interacts continuously with the host and its diet. Studying these interactions and their evolution in vivo as soon as they happen have been impossible. Here we develop a method to study microbiota-host-diet interactions continuously, non-invasively, and in real time, by measuring hydrogen (H2) and methane (CH4) production in mice housed in indirect calorimetry chambers.
Ademtest toont hoe bacteriën werken
Schothorst, Evert van - \ 2018
Direct and Long-Term Metabolic Consequences of Lowly vs. Highly-Digestible Starch in the Early Post-Weaning Diet of Mice
Fernández-Calleja, José M.S. ; Bouwman, Lianne M.S. ; Swarts, Hans J.M. ; Oosting, Annemarie ; Keijer, Jaap ; Schothorst, Evert M. van - \ 2018
Nutrients 10 (2018)11. - ISSN 2072-6643
adipose tissue - amylopectin - amylose - C57BL mice - carbohydrates - glycemic index - indirect calorimetry - metabolic flexibility - nutrition - sexual dimorphism

Starches of low and high digestibility have different metabolic effects. Here, we examined whether this gives differential metabolic programming when fed in the immediate post-weaning period. Chow-fed mice were time-mated, and their nests were standardized and cross-fostered at postnatal days 1⁻2. After postnatal week (PW) 3, individually housed female and male offspring were switched to a lowly-digestible (LDD) or highly-digestible starch diet (HDD) for three weeks. All of the mice received the same high-fat diet (HFD) for nine weeks thereafter. Energy and substrate metabolism and carbohydrate fermentation were studied at the end of the HDD/LDD and HFD periods by extended indirect calorimetry. Glucose tolerance (PW 11) and metabolic flexibility (PW14) were analyzed. Directly in response to the LDD versus the HDD, females showed smaller adipocytes with less crown-like structures in gonadal white adipose tissue, while males had a lower fat mass and higher whole body fat oxidation levels. Both LDD-fed females and males showed an enlarged intestinal tract. Although most of the phenotypical differences disappeared in adulthood in both sexes, females exposed to LDD versus HDD in the early post-weaning period showed improved metabolic flexibility in adulthood. Cumulatively, these results suggest that the type of starch introduced after weaning could, at least in females, program later-life health.

Marginal selenium deficiency down-regulates inflammation-related genes in splenic leukocytes of the mouse
Kipp, A.P. ; Banning, A. ; Brigelius, R. ; Keijer, J. ; Schothorst, E.M. van - \ 2018
GSE117026 - PRJNA480872 - Mus musculus
Moderate selenium deficiency may lead to an impaired capacity to cope with health challenges. Functional effects of suboptimal selenium intake are not fully known, and biomarkers for an insufficient selenium supply are inadequate. We therefore fed mice diets of moderately deficient or adequate selenium intake for 6 weeks. Changes in global gene expression were monitored by microarray analysis in splenic leukocytes. Genes for four selenoproteins, Sepw1, Gpx1, Selh and Sep15, were the most significantly down-regulated in moderate selenium deficiency, and this was confirmed by quantitative polymerase chain reaction (qPCR). Classification of significantly affected genes revealed that processes related to inflammation, heme biosynthesis, DNA replication and transcription, cell cycle and transport were affected by selenium restriction. Down-regulation by moderate selenium deficiency of specific genes involved in inflammation and heme biosynthesis was confirmed by qPCR. Myeloperoxidase and lysozyme activities were decreased in selenium-restricted leukocytes, providing evidence for functional consequences. Genes for 31 nuclear factor (NF)-κB targets were down-regulated in moderate selenium deficiency, indicating an impaired NF-κB signaling. Together, the observed changes point to a disturbance in inflammatory response. The selenoproteins found here to be sensitive to selenium intake in murine leukocytes might also be useful as biomarkers for a moderate selenium deficiency in humans.
Four selenoproteins, protein biosynthesis, and Wnt signalling are particularly sensitive to limited selenium intake in mouse colon
Kipp, A. ; Banning, A. ; Brigelius, R. ; Keijer, J. ; Schothorst, E.M. van - \ 2018
GSE117025 - PRJNA480871 - Mus musculus
Selenium is an essential micronutrient. Its recommended daily allowance is not attained by a significant proportion of the population in many countries and its intake has been suggested to affect colorectal carcinogenesis. Therefore, microarrays were used to determine how both selenoprotein and global gene expression patterns in the mouse colon were affected by marginal selenium deficiency comparable to variations in human dietary intakes. Two groups of 12 mice each were fed a selenium-deficient (0.086mg Se/kg) or a selenium-adequate (0.15mg Se/kg) diet. After 6wk, plasma selenium level, liver, and colon glutathione peroxidase (GPx) activity in the deficient group was 12, 34, and 50%, respectively, of that of the adequate group. Differential gene expression was analysed with mouse 44K whole genome microarrays. Pathway analysis by GenMAPP identified the protein biosynthesis pathway as most significantly affected, followed by inflammation, Delta-Notch and Wnt pathways. Selected gene expression changes were confirmed by quantitative real-time PCR. GPx1 and the selenoproteins W, H, and M, responded significantly to selenium intake making them candidates as biomarkers for selenium status. Thus, feeding a marginal selenium-deficient diet resulted in distinct changes in global gene expression in the mouse colon. Modulation of cancer-related pathways may contribute to the higher susceptibility to colon carcinogenesis in low selenium status.
Prolonged intake of hyperproteic casein-based diet promotes a molecular environment leading to liver triacylglycerol deposition and increases markers of hepatic damage in rats
Schothorst, E.M. van; Keijer, J. ; Diaz, R. ; Palou, A. ; Oliver, P. - \ 2018
Introduction: High protein (HP) diets have been associated to body weight loss and positive metabolic effects on obese subjects. However, controversy exists on the effects of long-term intake of these diets, as more recent reports point to health risk and higher mortality. Liver is a key organ involved in macronutrient handling, thus, we aimed to analyse the effects of HP diets on liver metabolism and health.
Methods: We performed a transcriptome analysis on liver of healthy adult male Wistar rats fed for 4 months with a casein-rich HP diet and analysed adiposity and molecular parameters related to metabolic syndrome and liver injury.
Results: Compared to rats on a control diet, HP-fed animals, that ingested 2.3 times higher amount of protein than controls, showed a lower cumulative food intake and lower body weight; although this lower body weight was not related to decreased adiposity. HP-fed animals presented lower serum cholesterol levels and were apparently healthy according to parameters related to metabolic syndrome: no differences were found in circulating non-esterified fatty acids or triaclyglicerols (TG) in comparison to controls. In liver, long-term intake of the casein-rich diet had an impact on metabolic pathways related with amino acid uptake/metabolism and lipid synthesis, indicative of higher TG deposition. Liver transcriptomic analysis also revealed up-regulation of immune-related genes and changes in expression of genes involved in acid-base maintenance and oxidative stress, pointing to alterations in the pH balance due to the high acid load of the diet, which has been linked to liver/health damage. In line with these transcriptomic changes, clear functional signs of unhealthy effects, such increased liver TG content and increased serum markers of hepatic injury/inflammation (aspartate transaminase, C-reactive protein and TNF-alpha) were observed. Moreover, chronic intake of the HP diet produced a dramatic increase of hepatic HSP90, a marker of liver injury.
Conclusion: A drastic and prolonged increase in diet protein intake, resulting in a high acid load, induces a hepatic transcriptome signature reflecting increased TG deposition and increased levels of markers of liver/health injury.
Non-invasive continuous real-time in vivo analysis of microbial hydrogen production shows adaptation to fermentable carbohydrates in mice
Fernández-Calleja, José M.S. ; Konstanti, Prokopis ; Swarts, Hans J.M. ; Bouwman, Lianne M.S. ; Garcia-Campayo, Vicenta ; Billecke, Nils ; Oosting, Annemarie ; Smidt, Hauke ; Keijer, Jaap ; Schothorst, Evert M. van - \ 2018
Scientific Reports 8 (2018)1. - ISSN 2045-2322 - 16 p.

Real time in vivo methods are needed to better understand the interplay between diet and the gastrointestinal microbiota. Therefore, a rodent indirect calorimetry system was equipped with hydrogen (H2) and methane (CH4) sensors. H2 production was readily detected in C57BL/6J mice and followed a circadian rhythm. H2 production was increased within 12 hours after first exposure to a lowly-digestible starch diet (LDD) compared to a highly-digestible starch diet (HDD). Marked differences were observed in the faecal microbiota of animals fed the LDD and HDD diets. H2 was identified as a key variable explaining the variation in microbial communities, with specific taxa (including Bacteroides and Parasutterella) correlating with H2 production upon LDD-feeding. CH4 production was undetectable which was in line with absence of CH4 producers in the gut. We conclude that real-time in vivo monitoring of gases provides a non-invasive time-resolved system to explore the interplay between nutrition and gut microbes in a mouse model, and demonstrates potential for translation to other animal models and human studies.

Identification of early transcriptome-based biomarkers related to lipid metabolism in peripheral blood mononuclear cells of rats nutritionally programmed for improved metabolic health
Konieczna, J. ; Sánchez, J. ; Schothorst, E.M. van; Torrens, J.M. ; Bunschoten, J.E. ; Palou, M. ; Pico, C. ; Keijer, J. ; Palou, A. - \ 2018
GSE119955 - Rattus norvegicus - PRJNA490821
Moderate maternal calorie restriction during lactation protects rat offspring against obesity development in adulthood, due to an improved ability to handle and store excess dietary fuel. We used this model to identify early transcriptome-based biomarkers of metabolic health using peripheral blood mononuclear cells (PBMCs), an easily accessible surrogate tissue, by focusing on molecular markers of lipid handling. Male and female offspring of control and 20 % calorierestricted lactating dams (CR) were studied. At weaning, a set of pups was killed, and PBMCs were isolated for whole-genome microarray analysis. The remaining pups were killed at 6 months of age. CR gave lower body weight, food intake and fat accumulation, and improved levels of insulin and leptin throughout life, particularly in females. Microarray analysis of weaned rat PBMCs identified 278 genes significantly differentially expressed between control and CR. Among lipid metabolism-related genes, expression of Cpt1a, Lipe and Star was increased and Fasn, Lrp1 and Rxrb decreased in CR versus control, with changes fully confirmed by qPCR. Among them, Cpt1a, Fasn and Star emerged as particularly interesting. Transcript levels of Cpt1a in PBMCs correlated with their levels in WAT and liver at both ages examined; Fasn expression levels in PBMCs at an early age correlated with their expression levels in WAT; and early changes in Star expression levels in PBMCs correlated with their expression levels in liver and were sustained in adulthood. These findings reveal the possibility of using transcript levels of lipid metabolism-related genes in PBMCs as early biomarkers of metabolic health status.
Skeletal muscle Nr4a1 hypomethylation and gene induction reduce insulin sensitivity in sedentary maternal high-fat offspring
Schothorst, E.M. van; Schumann, Sara ; Stelt, I. van der; Dartel, D.A.M. van; Klaus, Susanne - \ 2018
Mus musculus - GSE104029 - PRJNA408062
Maternal high-fat consumption has negative effects on the offspring’s obesity/diabetes susceptibility and we hypothesize that epigenetic modifications in the skeletal muscle are partly responsible for this phenotype. To detect genes affected by maternal nutrition, offspring of low-fat (LF) and high-fat (HF) diet fed dams (C57BL/6 mice) received LF diet upon weaning and were sacrificed at an age of 6 or 25 weeks. M. quadriceps gene expression was investigated by microarray analysis revealing upregulation of the nuclear receptor Nr4a1 by maternal HF feeding. This was accompanied by promoter hypomethylation of CpG‑1408 which correlated with higher Nr4a1 gene expression at both ages. Offspring voluntary exercise training normalized Nr4a1 methylation/expression and ameliorated the negative effects of maternal HF feeding on insulin sensitivity. Overall, Nr4a1 expression correlated with higher insulin levels during oral glucose tolerance test and could, therefore, be involved in the programming offspring’s diabetes susceptibility.
A constraint-based model analysis of enterocyte mitochondrial adaptation to dietary interventions of lipid type and lipid load
Sinha, Neeraj ; Suarez-Diez, Maria ; Hooiveld, Guido J.E.J. ; Keijer, Jaap ; Santos, Vitor Martin dos; Schothorst, Evert M. van - \ 2018
Frontiers in Physiology 9 (2018). - ISSN 1664-042X
Constraint-based metabolic model - Enterocytes - High fat diet - Mitochondria - Mitochondrial dynamics - Omega-3 lipids

Computational modeling of mitochondrial adaptability and flexibility in the small intestine upon different nutritional exposures will provide insights that will help to define healthy diet interventions. Therefore, a murine enterocyte-specific mitochondrial constraint-based metabolic model (named MT_mmuENT127) was constructed and used to simulate mitochondrial behavior under different dietary conditions, representing various levels and composition of nutrients absorbed by the enterocytes in mice, primarily focusing on metabolic pathways. Our simulations predicted that increasing the fraction of marine fatty acids in the diet, or increasing the dietary lipid/carbohydrate ratio resulted in (i) an increase in mitochondrial fatty acid beta oxidation, and (ii) changes in only a limited subset of mitochondrial reactions, which appeared to be independent of gene expression regulation. Moreover, transcript levels of mitochondrial proteins suggested unaltered fusion-fission dynamics by an increased lipid/carbohydrates ratio or by increased fractions of marine fatty acids. In conclusion, our enterocytic mitochondrial constraint-based model was shown to be a suitable platform to investigate effects of dietary interventions on mitochondrial adaptation and provided novel and deeper insights in mitochondrial metabolism and regulation.

Weinig verschil in verteerbaarheid
Star, Laura ; Kwakernaak, Cees ; Mens, Annemarie ; Krimpen, Marinus van - \ 2018
De Pluimveehouderij 2018 (2018)6. - ISSN 0166-8250 - p. 22 - 24.
De verteringscoëfficiënten van gangbare grondstoffen voor leghennen kunnen ook worden toegepast op biologische grondstoffen. In onderzoek vonden Schothorst Feed Research en Wageningen Livestock Research slechts kleine verschillen in de verteerbaarheid van fosfor, stikstof en omzetbare energie tussen biologische en gangbare mengvoergrondstoffen voor leghennen.
Insulin sensitivity linked skeletal muscle Nr4a1 DNA methylation is programmed by the maternal diet and modulated by voluntary exercise in mice
Kasch, Juliane ; Kanzleiter, Isabel ; Saussenthaler, Sophie ; Schürmann, Annette ; Keijer, Jaap ; Schothorst, Evert van; Klaus, Susanne ; Schumann, Sara - \ 2018
Journal of Nutritional Biochemistry 57 (2018). - ISSN 0955-2863 - p. 86 - 92.
Perinatal maternal high-fat consumption is known to increase the obesity and type 2 diabetes susceptibility and to impair exercise performance in the offspring. We hypothesize that epigenetic modifications in the skeletal muscle are partly responsible for this phenotype. To detect skeletal muscle genes affected by maternal nutrition, male offspring of low-fat (LF) and high-fat (HF) diet fed dams (BL6 mice) received LF diet upon weaning and were sacrificed at 6 or 25 weeks of age. Gene expression of Musculus quadriceps was investigated by microarray analysis revealing an up-regulation of the nuclear receptor Nr4a1 by maternal HF feeding. This was accompanied by promoter hypomethylation of CpG-1408 which correlated with increased Nr4a1 gene expression at both ages. Offspring voluntary exercise training (by supplying running wheels from 7 to 25 weeks of age) normalized Nr4a1 methylation and gene expression respectively, and ameliorated the negative effects of maternal HF feeding on insulin sensitivity. Overall, Nr4a1 gene expression in skeletal muscle correlated with higher insulin levels during an oral glucose tolerance test and could, therefore, be involved in programming type 2 diabetes susceptibility in offspring exposed to perinatal high fat diet.
Fosforverteringscoefficienten grondstoffen
Mens, A.J.W. ; Jonge, L.H. de; Wikselaar, P.G. van; Bikker, P. ; Krimpen, M.M. van - \ 2018
V-focus 15 (2018)1. - ISSN 1574-1575 - 4 p.
In een onderzoek naar de voederwaarde en diervoedergrondstoffen, uitgevoerd door Wageningen Livestock Research in samenwerkin met Schothorst Feed Research, zijn een grote verschillen in verteerbaarheid van nutriënten gevonden tussen biologisch gehouden varkens te verbeteren kan intrinsiek fytase uit tarwe en tarwegries een uitkomst bieden.
No Adverse Programming by Post-Weaning Dietary Fructose of Body Weight, Adiposity, Glucose Tolerance, or Metabolic Flexibility
Bouwman, Lianne M.S. ; Fernández-Calleja, José M.S. ; Swarts, Hans J.M. ; Stelt, Inge van der; Oosting, Annemarie ; Keijer, Jaap ; Schothorst, Evert M. van - \ 2018
Molecular Nutrition & Food Research 62 (2018)2. - ISSN 1613-4125
carbohydrates - indirect calorimetry - metabolic programming - metabolism - monosaccharides
Scope: Metabolic programming can occur not only in the perinatal period, but also post-weaning. This study aims to assess whether fructose, in comparison to glucose, in the post-weaning diet programs body weight, adiposity, glucose tolerance, metabolic flexibility, and health at adult age. Methods and results: Three-week-old male and female C57BL6/JRccHsd mice are given an intervention diet with 32 energy percent (en%) glucose or fructose for only 3 weeks. Next, all animals are switched to the same 40 en% high fat diet for 9 weeks. Neither body weight nor adiposity differs significantly between the animals fed with glucose or fructose diets at any point during the study in both sexes. Glucose tolerance in adulthood is not affected by the post-weaning diet, nor are activity, energy expenditure, and metabolic flexibility, as measured by indirect calorimetry. At the end of the study, only in females fasting serum insulin levels and HOMA-IR index are lower in post-weaning fructose versus glucose diet (p = 0.02), without differences in pancreatic β-cell mass. Conclusions: Our present findings indicate no adverse programming of body weight, adiposity, glucose tolerance, and metabolic flexibility by dietary (solid) fructose in comparison to glucose in the post-weaning diet in mice.
Effect of dietary lipid structure in early life improves metabolic function of adult adipose tissue in mice
Baars, Annemarie ; Schipper, Lidewij ; Mischke, M. ; Klein Hazebroek, Marlou ; Schothorst, E.M. van; Beek, Eline van der; Oosting, Annemarie - \ 2017
Journal of Developmental Origins of Health and Disease 8 (2017)Supplement 1. - ISSN 2040-1744 - p. S52 - S53.
Monosaccharides in post-weaning diet of young mice program body composition and feeding behaviour in adulthood
Fernández Calleja, J.M.S. ; Bouwman, L.M.S. ; Swarts, J.J.M. ; Oosting, Annemarie ; Keijer, J. ; Schothorst, E.M. van - \ 2017
Journal of Developmental Origins of Health and Disease 8 (2017)Supplement 1. - ISSN 2040-1744 - p. S369 - S369.
Metabolic homeostasis in the cold requires neither FGF21 nor UCP1
Keipert, Susanne ; Kutschke, Maria ; Ost, Mario ; Schwarzmayr, Thomas ; Schothorst, E.M. van; Lamp, Daniel ; Brachthäuser, Laura ; Graf Pannatier, Elisabeth ; Neff, Frauke ; Jastroch, Martin - \ 2017
Transcriptomic analysis reveals a strong down regulation of immune response pathways in ferret aortic perivascular adipose tissue by cold exposure: potential implications of cardiovascular health
Reynés, Bàrbara ; Schothorst, E.M. van; García-Ruiz, Estefanía ; Keijer, J. ; Palou, Andreu ; Oliver, Paula - \ 2017
No adverse post-weaning programming by fructose of body weight, adiposity, glucose tolerance and metabolic flexilibility
Bouwman, L.M.S. ; Fernández Calleja, J.M.S. ; Keijer, J. ; Oosting, A. ; Schothorst, E.M. van - \ 2017
Nutritional effects by beta-carotene in lung in males and females of control mice versus BCMO knockout mice
Schothorst, E.M. van; Helden, Y.G.J. ; Keijer, J. ; Bunschoten, J.E. ; Lintig, J. von; Lietz, G. - \ 2017
Mus musculus - GSE98845 - PRJNA386385
Molecular mechanisms triggered by high dietary beta-carotene (BC) intake in lung are largely unknown. We performed microarray gene expression analysis on lung tissue of BC supplemented beta-carotene 15,150-monooxygenase 1 knockout (Bcmo1-/-) mice, which are—like humans—able to accumulate BC. Our main observation was that the genes were regulated in an opposite direction in male and female Bcmo1-/- mice by BC. The steroid biosynthetic pathway was overrepresented in BC-supplemented male Bcmo1-/- mice. Testosterone levels were higher after BC supplementation only in Bcmo1-/- mice, which had, unlike wild-type (Bcmo1+/+) mice, large variations. We hypothesize that BC possibly affects hormone synthesis or metabolism. Since sex hormones influence lung cancer risk, these data might contribute to an explanation for the previously found increased lung cancer risk after BC supplementation (ATBC and CARET studies). Moreover, effects of BC may depend on the presence of frequent human BCMO1 polymorphisms, since these effects were not found in wild-type mice.
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